HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Figures Only Full Text (PDF) Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Preuss, H. G. Articles by Knapka, J. Search for Related Content PubMed PubMed Citation Articles by Preuss, H. G. Articles by Knapka, J.

Sugar-Induced Blood Pressure Elevations Over the Lifespan of Three Substrains of Wistar Rats

Nephrology Division (H.G.P., M.Z., P.M.), Georgetown University Medical Center, Washington, DC
Department of Medicine, Georgetown University Medical Center, Washington, DC
University of Texas Medical Branch (D.P.), Galveston, Texas
Nephropathology Section (S.S.), Brookville, Maryland
Walter Reed Army Institute of Pathology, Washington DC; and (J.K.), Brookville, Maryland

Address reprint requests to: Harry G. Preuss MD, FACN, Georgetown University Medical Center, Bldg D, Rm 371, 4000 Reservoir Road, NW, Washington, DC 20007

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIAL AND METHODS RESULTS DISCUSSION REFERENCES

 
Objective: Since the majority of studies concerned with sugar-induced blood pressure elevation have principally been short-term, the present investigation followed the effects of heavy sucrose ingestion on systolic blood pressure (SBP) and related parameters over the lifespan of three substrains of Wistar rats.

Methods: Two hundred twenty-five rats (75 spontaneously hypertensive rats (SHR), 75 Wistar Kyoto rats (WKY), 75 Munich Wistar rats (WAM)) were given one of five diets. The baseline diet in terms of calories derived 32% from sucrose, 33% from protein, and 35% from fat. The remaining four diets derived their calories as follows: a high sugar-low protein diet—52% of calories from sucrose, 15% from protein, and 33% from fat; a high sugar-low fat diet—53% of calories from sucrose, 37% from protein, and 10% from fat; a low sugar-high protein diet—11% calories from sucrose, 56% from protein, and 33% from fat, and a low sugar-high fat—13% of calories from sucrose, 32% from protein, and 55% from fat.

Results: All substrains showed the highest systolic blood pressure when ingesting the two diets highest in sucrose. The highest sugar-induced SBP elevation, which remained over the lifespan of all substrains, was found in SHR. WKY had an intermediate elevation. WAM showed the lowest responses, although the average elevation of 6–8 mm Hg was statistically significant. The following parameters could not be correlated with long-term elevation of SBP: body weight, catecholamine excretion, renal function, and plasma renin activity. Only insulin concentrations correlated: insulin concentrations were consistently higher in the two groups of WKY and WAM consuming the high sucrose diets.

Conclusions: High dietary sucrose can chronically increase SBP in three substrains of Wistar rats. Increased concentrations of circulating insulin were found in WKY and WAM suggesting that the glucose/insulin system was involved, at least in these two substrains, in the maintenance of high SBP levels during chronic, heavy sugar ingestion.

Key words: Hypertension: sugar-induced, insulin perturbations, hypertension

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIAL AND METHODS RESULTS DISCUSSION REFERENCES

 
Early studies examining the possibility that high dietary sugar consumption influences blood pressure (BP) were inconclusive. In the 1960’s, Hall and Hall [1] added various sugars to saline to increase consumption of salt. Increased BP occurred only with ingestion of certain sugars, and the phenomenon was attributed to greater intake of salt (NaCl) rather than any direct effect of sugars. In 1976, Beebe et al [2] compared the ability of four diets described as "grain, high sucrose, high fat, and high protein" to alter BP. Only one of two experiments showed any statistically significant differences: rats consuming the high sucrose diet had a statistically significant increase in BP compared to rats consuming the grain diet. However, these studies did not show a significant difference in BP between the high sugar and the high fat/high protein groups. Accordingly, whether the sugar content or some other dietary constituents, such as fibers, were responsible for the differences between the grain and sugar diets was uncertain.

In 1980, Preuss and Preuss [3] and Ahren et al [4] reported that increased consumption of sucrose directly increased systolic BP (SBP) whether exchanges of sucrose were made with fat, protein, or starch. The former study, using three substrains of Wistar rats (SHR, WKY, and WAM), showed that different substrains had different sensitivities to sucrose and indicated that there was a positive interaction between sugar and salt on SBP [3]. Many papers followed corroborating that SBP of various rat strains, principally SHR and Sprague-Dawley, were affected by sucrose, fructose, and glucose [5–10]. Sugar-induced BP elevations have also been found in dogs [11] and primates [12], but data on humans reveal no clear answers.

Studies on sugar-induced BP elevations have principally been short-term, limited to observations over months. Only a few long-term studies, i.e., 1 year or longer, have been reported [13–16]. Therefore, some uncertainty exists concerning chronic effects of high sugar ingestion on BP and other cardiovascular parameters. The present investigation followed the effects of high sucrose ingestion on SBP and related parameters over the lifespan of three substrains of Wistar rats: SHR, WKY, and WAM. Measurements were made to gain insight into mechanisms regulating dietary influence on BP over a long period of time.

	MATERIAL AND METHODS

TOP ABSTRACT INTRODUCTION MATERIAL AND METHODS RESULTS DISCUSSION REFERENCES

 
Two hundred twenty-five male rats of three Wistar substrains, 75 rats in each group, were obtained at 6 weeks of age from Taconic Farms, Germantown, NY. As in an earlier paper [3], these included spontaneously hypertensive rats (SHR), Wistar Kyoto rats (WKY), and locally raised Munich Wistar rats which we have designated WAM. All rats ingested laboratory rat chow until they were 3 months of age. The rats were then fed for their lifetime one of the five diets differing in the concentrations of macronutrients. Accordingly, the three substrains contained five dietary groups consisting of 15 rats.

The experimental diets have been described as diets I through V in previous communications (Table 1) [17]: I=baseline, where virtually equal calories were derived from sucrose, fats, and proteins, II=High Sugar-Low Protein (HS-LP), III=High Sugar-Low Fat (HS-LF), IV=Low Sugar-High Protein (LS-HP), and V=Low Sugar-High Fat (LS-HF). For ease, the diets will be referred to as: baseline, HS-LP, HS-LF, LS-HP, and LS-HF. The percentage of energy contributed by sugar (sucrose), protein and fats was the variables of interest. The largest percentage of energy was contributed by sucrose (>50%) in the HS-LP and HS-LF diets, while protein and fats contributed the smallest percentage of calories respectively. The sucrose fraction provided the lowest percentage of calories in the LS-HP and LS-HF diets and protein and fats the highest, respectively. Minerals, electrolytes, and vitamins were virtually the same in all diets. These diets were relatively low salt, because sodium content was 0.11 to 0.13% w/w instead of 0.30 to 0.40% w/w in most commercial feeds.

Urine was collected by placing the rats in special steel metabolic cages for 24 hours. Urine volume was measured, and the urine was assayed for proteins, creatinine, sodium, and potassium by routine clinical procedures. Creatinine clearance was estimated from a 24-hour urine specimen, and the serum creatinine analyzed on a blood specimen obtained within days of the urine collection.

Blood was collected from tails. Blood chemistries were performed by routine clinical procedures. PRA, catecholamines, and insulin were measured by RIA [9,17].

Histology by light microscopy was interpreted and scored by one of the authors (SS) [19]. Renal tissue was obtained from five rats in each dietary group of SHR and WKY. The tissue was fixed in 10% buffered formalin. Three micron sections were stained with hematoxylin-eosin. The glomerular, vascular, tubular, and interstitial changes were graded from 0 to 3 (0=no change, 3=maximum changes).

Statistical evaluation of SBP and BW was assessed by two-way analysis of variance (ANOVA) (one factor being diet and the second factor being time of examination) by factorial measures. Measurements were discontinued if the number of rats in any dietary group dropped below one-half. For blood, urinary, and tissue determinations, not all rats were checked. Those rats included in these measurements were selected at random among the larger groups. Where a significant effect of diet was detected by ANOVA, Dunnett’s t-test [20] was used to establish which differences between means reached statistical significance. When two columns were analyzed, the unpaired Students’ t test (two tail) was used. Statistical significance was set at p<0.05.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIAL AND METHODS RESULTS DISCUSSION REFERENCES

 
Systolic Blood Pressure (Fig. 1)
The general trend among all dietary groups was for the SBP to rise during early life and then decrease with age. SBP were measured at 3-month intervals. Among all three substrains of Wistars (SHR, WKY, and WAM), those rats ingesting diets high in sucrose, i.e., HS-LP and HS-LF (52% and 53% of calories from sucrose respectively), eventually showed statistically higher SBP over their lifespan compared to those consuming the baseline, LS-HP, and LS-HF diets, which contained lesser amounts of sucrose (Fig. 1). Although containing relatively more sucrose (32% calories), the average SBP of rats consuming the baseline diet never significantly exceeded SBP of rats consuming the LS-HP and LS-HF diets (11% and 13% of calories from sucrose respectively). The time scale of the abscissa in Fig. 1 shows age. Special diets were begun at 3 months of age of rats. Accordingly, time frame ingesting special diets will be 3 months less than age.

View larger version (19K): [in this window] [in a new window]   Fig. 1. Body weights over lifespan of SHR, WKY, and WAM. Means±SEM are depicted. Closed circles represent rats consuming High Sugar-Low Protein; closed squares represent Hi Sugar-Low Fat; stars represent baseline; open circles represent Low Sugar-High Protein; and open squares represent Low Sugar-High Fat. A minimum of nine rats per group was analyzed statistically.

WKY.
Significant SBP elevations caused by heavy sugar consumption (HS-LP, HS-LF) were found 3 months following consumption of the special diets at age 6 months, and remained over the next 2 years. Differences were maintained at a level of 10–20 mm Hg above the other three dietary groups (baseline, LS-HP, LS-HF). SBP of WKY, considered a normotensive substrain, in time, averaged over 150 mm Hg in the two groups consuming high sucrose diets (HS-LP, HS-LF). In contrast to SHR, WKY consuming diet HS-LF had significantly higher SBP than those consuming diet HS-LP at 18 and 24 months of age.

WAM.
Significant elevations of SBP in WAM consuming diets HS-LP and HS-LF were delayed until the measurements made after 6 months of consuming special diets, at age 9 months. Thereafter, the average increase remained between 6–12 mm Hg. The SBP of SHR ingesting diets HS-LP and HS-LF were not significantly different from each other throughout the life span of these rats.

Body Weight (BW) (Fig. 2)
In all three substrains, the general trend was for the three dietary groups LS-HF, HS-LP, and baseline to have relatively higher BW after 1 year or, at least, by the end of study, than the other two groups (HS-LF and LS-HP). Comparing the three diets associated with higher body weights (baseline, HS-LP, LS-HF), baseline caused a relatively, smaller weight gain in WKY, and diet HS-LP was relatively less in WAM. Among all five diets, the lowest body weights were consistently found in the LS-HP and HS-LF groups, with rats consuming diet LS-HP showing the lowest weights in WKY and WAM.

View larger version (18K): [in this window] [in a new window]   Fig. 2. Systolic blood pressures over lifespan of SHR, WKY, and WAM. Means±SEM are depicted. Closed circles represent rats consuming High Sugar-Low Protein; closed squares represent Hi Sugar-Low Fat; stars represent baseline; open circles represent Low Sugar-High Protein; and open squares represent Low Sugar-High Fat. A minimum of nine rats per group was analyzed statistically.

Catecholamine Excretion (Table 2)
No consistent differences in norepinephrine, epinephrine, and dopamine excretion were seen among the high sucrose consumers of the three substrains of Wistar rats measured after 6 and 12 months. Norepinephrine, epinephrine, and dopamine excretion were not significantly higher in groups HS-LP and HS-LF compared to other groups at the times measurements were made.

Renal Histology (Table 7)
Renal histology was examined and scored in SHR and WKY. In each strain, five rats from each dietary group were examined. Among the general parameters assessed, few consistent differences between dietary groups were seen. SHR ingesting HS-LP had more glomerular lesions than SHR consuming the baseline, HS-LF, and LS-HF diets. In WKY rats consuming HS-LF, more interstitial changes were present than in rats consuming diets HS-LP, LS-HP, and LS-HF; and also more artery and arteriole changes were present in rats consuming HS-LF than the other groups. Suffice it to say, no consistent changes in the renal histology of SHR and WKY rats consuming both HS-LP and HS-LF compared to the other groups were seen to explain the higher SBP in these two groups.

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIAL AND METHODS RESULTS DISCUSSION REFERENCES

The present study examines the sugar induction phenomenon over lifespan rather than over a few months. The most important finding in the present study is that sucrose-induced elevations of SBP initiated early remain over the lifespan of three substrains of Wistar rats. Although all substrains eventually showed an augmented SBP response to the two diets highest in sucrose concentration (HS-LP, HS-LF) (>50% of calories from sucrose) compared to the three diets deriving less calories from sucrose, the SBP response of each substrain differed to some extent. The sugar-induced elevation of SBP was present by the first reading (3 months consuming special diets) in SHR and WKY, but not WAM. It was not until after 6 months of eating special diets that a significant elevation in SBP occurred in WAM. In addition, SBP elevations throughout the lifetime of the rats was greatest in SHR, intermediate in WKY, and least in WAM.

It should be emphasized that the special diets were relatively low in sodium, containing approximately one-third the amount added to normal laboratory diets. This explains, at least in part, the lack of SBP elevation seen with the baseline diet (36% calories from sucrose). Previous studies have shown that the presence of normal dietary sodium is associated with SBP elevations at these same lower concentrations of sucrose [24]. For example, diets deriving 18% of calories from sucrose, comparable to the amount of sugar (mostly sucrose and fructose) present in the average American diet, can augment SBP in SHR in the presence of normal quantities of dietary sodium [25]. Nevertheless, it was the purpose of this study to focus on the effects of sucrose rather than sodium over the long term on SBP.

Many mechanisms have been proposed for the pathogenesis of sugar-induced hypertension [34]. However, the pathogenesis of sugar-induced hypertension over long-term could differ from that present initially, i.e., initiation and maintenance could be caused principally by different mechanisms. What do the data obtained in the present study suggest as possibilities for mechanisms causing hypertension over long term?

Body weight does not appear to be a major factor in the development of acute SBP elevation [3], and this is true also in the chronic maintenance phase. Comparing data in Tables 1 and 2 reveals no obvious trends. Elevations in SBP were not associated with increased weight gain. The lowest weight gains were seen in rats consuming LS-HP and HS-LF. However, the former showed relatively low SBP; while the latter diet was associated with a relatively elevated SBP. Because there is a lack of correlation between SBP and BW, fluid retention is less likely to be important in the pathogenesis [35]. However, this possibility cannot be ruled out entirely, because gain in fluid weight could be counterbalanced by loss of solid mass. Examination of serum potassium, calcium, and magnesium concentrations at the various time intervals suggests that perturbations in these elements are not responsible for the chronic elevation in SBP (Table 4). Concerning magnesium, urinary excretory studies have suggested a decreased systemic level of magnesium in SHR consuming sugar [32], and magnesium loading has been shown to prevent elevations of SBP following sugar challenge [36]. However, circulating magnesium concentrations were lowest in the LS-HP and LS-HF groups which showed the lowest SBP. Further examination of BUN and serum creatinine, creatinine clearance, and urinary protein excretion indicate that renal damage is not playing a major role in sugar-induced BP elevations.

Despite much investigation, no single explanation behind the pathogenesis of sugar-induced blood pressure elevations has come to the fore [34,35]. Some of those considered previously will be discussed briefly in light of the current data.

Our data do not allow us to definitively rule in or rule out the catecholamine or renin-angiotensin systems in the pathogenesis. Many studies on acute sugar-induction have implicated perturbed catecholamine metabolism in the pathogenesis [5,7]. However, relative differences in catecholamine excretion were not brought on by the different diets over the long term (Table 2). The role of the renin-angiotensin system has been postulated to be important based on studies using the angiotensin receptor blocker—losarten. Losarten is known to lower BP elevated by sugar ingestion [33]. Nevertheless, we found no consistent differences in the circulating PRA to implicate this system in the pathogenesis. SHR consuming high sugar diets had elevated circulating PRA, but WKY consuming high sugar diets had lower circulating PRA. However, in subsequent acute studies, it was shown that circulating angiotensin II concentrations rose with high sucrose consumption, at least in SHR [37]. Accordingly, the role of the renin-angiotensin in sugar-induced hypertension cannot be ruled out entirely. Furthermore, high circulating levels of angiotensin II have been associated with insulin resistance as discussed below [33].

Insulin levels are a crude measure of peripheral insulin resistance [38]. This is important, since insulin resistance may play a greater role in the development of high BP than hyperinsulinemia itself [39]. Recently much emphasis has been placed on the role of a perturbed insulin system, especially insulin resistance, in essential hypertension [40]. Heavy sugar ingestion is associated with insulin resistance, hyperinsulinemia, and hypertension, as well as many perturbations associated with hypertension—obesity, lipid abnormalities, platelet disturbances, and hyperuricemia [39–47]. Perturbed insulin metabolism is commonly seen in patients with hypertension, while hypertension is also more prevalent among diabetics [43,48,49]. In Sprague-Dawley rats, heavy fructose ingestion has been associated with disturbances in insulin metabolism that can be reversed by somatostatin [50]. Somatostatin may favorably affect the insulin system. Other studies showing that agents overcoming insulin resistance decrease sugar-induced BP elevations are supportive. Metformin [30], troglitazone [31], vanadium [28,29], and chromium [27] ameliorate sugar-induced BP elevations. However, many of these agents, with the exception of chromium, have known BP-lowering effects independent of changes in insulin sensitivity. Nevertheless, the results with chromium, an agent currently believed only to influence the insulin system [27], makes it hard to state that high circulating levels of angiotensin II are causing the elevation in BP and the insulin resistance is only a secondary result [33].

How could a perturbed insulin resistance influence BP? Many hypotheses have been given. Insulin resistance is associated with defects in membrane sodium and calcium transport. The sodium, potassium-ATPase and calcium-ATPase pumps are influenced by insulin [39]. When insulin resistance is present, activity of these pumps in smooth muscle of arteries might be reduced. A secondary accumulation of sodium and calcium could sensitize the vasculature to pressor agents [39].

Hyperinsulinemia may also be important in the pathogenesis. Insulin is antinatriuretic. A direct antinatriuretic effect of insulin has been found in isolated dog kidneys and in human diabetics treated with insulin [40,51]. DeFronzo [51] reported that insulin increased renal sodium reabsorption without altering glomerular filtration rate. In addition, resistance to insulin-stimulated glucose uptake is not associated with resistance to antinatriuretic effects of insulin. Therefore, insulin may increase BP directly through its ability to stimulate renal sodium reabsorption. Stimulation of the catecholamine system is another means through which insulin could influence BP [7,52]. In the absence of hypoglycemia, insulin stimulates the sympathetic nervous system [53]. Although some studies have failed to show that insulin infusions directly elevate BP, it may be that the additional element of insulin resistance is needed.

In summary, the initial magnitude of SBP elevation induced by heavy sucrose ingestion remains throughout the lifespan of three substrain of Wistar rats. SHR proved most sensitive: a response was seen at three months and caused an elevation of SBP of 20 mm Hg. WKY also had a significant response to sucrose at 3 months and showed an average elevation of 10 to 15 mm Hg, which was not as dramatic as SHR. An increase in SBP was not seen in WAM until 6 months after initiating the dietary regimens, and the average elevation approximated only 8 mm Hg. In all substrains changes in SBP did not correlate with BW: the lowest BW were found in rats consuming the high sugar-low fat and low sugar-high protein diets. Examining mechanisms behind chronic induction of sucrose-induced SBP elevations, the data did not implicate changes in body weight, fluid retention, renal damage, catecholamine metabolism, and the renin-angiotensin system in the pathogenesis although any of these factors might still play some role. However, circulating concentrations of insulin were elevated suggesting that perturbations in the glucose/insulin system could be responsible for the sugar-induced elevations of SBP [27].

	ACKNOWLEDGMENTS

 
Supported by NRICGP/USDA 9201419 and NIH grant AG 06929.

Received October 1, 1996. Revised July 1, 1997. Accepted July 1, 1997.

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIAL AND METHODS RESULTS DISCUSSION REFERENCES

 

1. Hall CE, Hall O: Comparative effectiveness of glucose and sucrose in enhancement of hypersalimentation and salt hypertension. Proc Soc Exper Biol Med 123: 370–374, 1966.[Medline]
2. Beebe CG, Schemmel R, Michelson O: Blood pressure of rats as affected by diet. Proc Soc Exper Biol Med 151: 395–399, 1976.[Medline]
3. Preuss MB, Preuss HG: Effects of sucrose on the blood pressure of various strains of Wistar rats. Lab Invest 43: 101–107, 1980.[Medline]
4. Ahrens RA, Demuth P, Lee MK, Majkowski JW: Moderate sucrose ingestion and blood pressure in rat. J Nutr 110: 725–731, 1980.
5. Bunag RD, Tomita T, Sasaki S: Chronic sucrose ingestion induces mild hypertension and tachycardia in rats. Hypertension 5: 218–225, 1983.[Abstract/Free Full Text]
6. Fields M, Ferretti RJ, Smith JC, Reiser S: Effect of dietary carbohydrate and copper status on blood pressure in rats. Life Sci 34: 763–769, 1984.[Medline]
7. Fournier RD, Chiueh CC, Kopin IJ, Knapka JJ, DiPette D, Preuss HG: The interrelationship between excess CHO ingestion, blood pressure and catecholamine excretion in SHR and WKY. Am J Physiol 250: E381–E385, 1986.[Abstract/Free Full Text]
8. Michaelis OE, Martin RE, Gardener LB, Ellwood KC: Effect of dietary carbohydrates on systolic blood pressure of normotensive and hypertensive rats. Nutr Rep Int 23: 261–266, 1981.
9. Preuss HG, Zein M, Knapka J, MacArthy P, Yousufi AK, Gleim GW, Glace B, Zukowska-Grojec Z: Blood pressure responses to sucrose ingestion in four strains of rats. Am J Hypertens 5: 244–250, 1992.[Medline]
10. Young JB, Landsberg L: Effect of oral sucrose on blood pressure in the spontaneously hypertensive rat. Metabolism 30: 421–424, 1981.[Medline]
11. Martinez FJ, Rizza RA, Romero JC: High-fructose feeding elicits insulin resistance, hyperinsulinism, and hypertension in normal mongrel dogs. Hypertension 23: 456–463, 1994.[Abstract/Free Full Text]
12. Srinivasan SR, Berenson GS, Radhakrishnamurthy B, Dalferes ER Jr, Underwood D, Foster TA: Effect of dietary sodium and sucrose on induction of hypertension in the spider monkey. Am J Clin Nutr 33: 561–569, 1980.[Free Full Text]
13. Park SK, Meyer TW: The effect of fructose feeding on glomerular structure in the rat. J Am Soc Nephrol 3: 1330–1332, 1992.[Medline]
14. Preuss HG, Zein M, Areas JL, Gao CY: Macronutrients in the diet: a possible association with age related hypertension. In Armbrecht TJ, Coe R, Wongsurawat N (eds.) "Endocrine Function and Aging." New York, NY: Springer-Verlag, pp 161–174, 1990.
15. Vrana A, Kazdova L, Dobesova Z, Kunes J, Kren V, Bila V, Stolba P, Klimes I: Triglyceridemia, glucoregulation, and blood pressure in various rat strains. Ann N Y Acad Sci 683: 57–68, 1993.[Medline]
16. Zein M, Areas JL, Preuss HG: Chronic effects of excess sucrose ingestion on 3 strains of rats. Am J Hypertens 3: 560–562, 1990.[Medline]
17. Zein M, Areas JL, Knapka J, MacArthy P, Yousufi AK, DiPette D, Holland B, Goel R, Preuss HG: Excess sucrose and glucose ingestion acutely elevate blood pressure in spontaneously hypertensive rats. Am J Hyper 3: 380–386, 1990.[Medline]
18. Bunag RD: Validation in awake rats of a tail cuff method for measuring systolic pressure. J Appl Physiol 34: 279–282, 1973.[Free Full Text]
19. Preuss HG, Zein M, Areas JL, Podlasek SJ, Knapka J, Antonovych TT, Sabnis SG, Zepeda H: Effects of excess sucrose ingestion on the life span of hypertensive rats. Ger Nephrol Urol 1: 13–20, 1991.
20. Dunnett C: A multiple comparison procedure for comparing several treatments with control. J Am Statis Assoc 50: 1096–1121, 1955.
21. Preuss HG, Fournier RD, Preuss J, Zein M, Garcia C, Knapka J: Effects of different refined carbohydrates on the blood pressure of SH and WKY rats. J Clin Biochem Nutr 5: 9–20, 1988.
22. Hulman S, Falkner B: The effect of excess dietary sucrose on growth, blood pressure, and metabolism in developing Sprague-Dawley rats. Ped Res 36: 95–101, 1994.[Medline]
23. Preuss HG, Knapka JJ: Sugar-induced hypertension in Fischer 344 and F1-hybrid at different ages. J Ger Nephrol Urol 4: 15–21, 1994.
24. Preuss HG: Interplay between sugar and salt on blood pressure of SHR. Nephron 68: 385–387, 1994.[Medline]
25. Gondal JA, MacArthy P, Myers AK, Preuss HG: Effects of dietary sucrose and fibers on blood pressure in spontaneously hypertensive rats. Clin Neph 45: 163–168, 1996.
26. Zein M, Areas J, Knapka J, Gleim G, DiPette D, Holland B, Preuss HG: Influence of oat bran on sucrose-induced blood pressure elevations in SHR. Life Sci 47: 1121–1128, 1990.[Medline]
27. Preuss HG, Gondal JA, Bustos E, Bushehri N, Lieberman S, Bryden NA, Polansky MM, Anderson RA: Effect of chromium and guar on sugar-induced hypertension in rats. Clin Neph 44: 170–177, 1995.
28. Bhanot S, McNeill JH: Vanadyl sulfate lowers plasma insulin and blood pressure in spontaneously hypertensive rats. Hypertension 24: 625–632, 1994.[Abstract/Free Full Text]
29. Bhonot S, McNeill JH, Bryer-Ash M: Vanadyl sulfate prevents fructose-induced hyperinsulinemia and hypertension in rats. Hypertension 23: 308–312, 1994.[Abstract/Free Full Text]
30. Verma S, Bhanot S, McNeill JH: Antihypertensive effects of metformin in fructose-fed hyperinsulinemic hypertensive rats. J Pharmacol Exper Ther 271: 1334–1337, 1994.[Abstract/Free Full Text]
31. Lee M-K, Miles PDG, Khoursheed M, Gao K-M, Moossa AR, Olefsky JM: Metabolic effects of troglitazone on fructose-induced insulin resistance in the rat. Diabetes 43: 1435–1439, 1994.[Abstract]
32. Preuss HG, Memon S, Dadgar A, Jiang G: Effects of diets high in sugar on renal fluid, electrolyte, and mineral handling in SHR: Relationship to blood pressure. J Am Coll Nutr 13: 73–82, 1994.[Abstract]
33. Iyer SN, Katovich MJ: Effects of losarten potassium treatment on fructose-induced hypertension. Life Sci 55 PL: 130–134, 1994.
34. Preuss HG, Fournier RD: Effects of sucrose ingestion on blood pressure. Life Sci 30: 878–886, 1982.
35. Karanja N, McCarron DA: Effects of dietary carbohydrates on blood pressure. Prog Biochem Pharmacol 21: 248–265, 1986.[Medline]
36. Balon TW, Jasman A, Scott S, Meehan WP, Rude RK, Nadler JL: Dietary magnesium prevents fructose-induced insulin insensitivity in rats. Hypertension 23: 1036–1039, 1994.[Abstract/Free Full Text]
37. Jarrell ST, Bushehri N, Shi S-J, Andrawis NB, Clouatre D, Preuss HG: Effects of wild garlic (Allium Ursinum) on blood pressure (BP) in spontaneously hypertensive rats (SHR). (Abstract). J Am Coll Nutr 15: 532, 1996.
38. DeFronzo RA, Ferrannini E: Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14: 173–194, 1991.[Abstract]
39. Sower JR: Is hypertension an insulin-resistant state? Metabolic changes associated with hypertension and antihypertensive therapy. Am Heart J 122: 932–935, 1991.[Medline]
40. Ferrannini E, Buzzigoli G, Bonadonna R, Gioraico MA, Oleggini M, Graziadei L, Pedrinelli R, Brandi L, Bevilacqua S: Insulin resistance in essential hypertension. N Engl J Med 317: 350–357, 1987.[Abstract]
41. Fournier AM, Gadia MT, Kubrusly DB, Skyler JS, Sosenko JM: Blood pressure, insulin, and glycemia in nondiabetic subjects. Am J Med 80: 861–864, 1983.
42. Reaven GR: Effects of differences in amount and kind of dietary carbohydrates on plasma glucose and insulin responses in man. Am J Clin Nutr 32: 2568–2578, 1979.[Abstract/Free Full Text]
43. Reaven GM, Hoffman BB: A role for insulin in the aetiology and course of hypertension? Lancet ii: 435–436, 1987.
44. Reiser S, Handler HB, Gardner LB, Hallfrisch JG, Michaelis OE, Prather ES: Isocaloric exchange of dietary starch and sucrose in humans. II. Effect on fasting blood insulin, glucose, and glucagon and on insulin and glucose response to a sucrose load. Am J Clin Nutr 32: 2206–2216, 1979.[Abstract/Free Full Text]
45. Shen DC, Shieh SM, Fuh MM, Wu DA, Chen YPI, Reaven GM: Resistance to insulin stimulated glucose uptake in patients with hypertension. J Clin Endocrinol Metab 66: 580–583, 1988.[Abstract/Free Full Text]
46. Solt VB, Brown MR, Kennedy B, Kolterman OG, Ziegler MG: Elevated insulin, norepinephrine, and neuropeptide Y in hypertension. Am J Hypertens 3: 823–828, 1990.[Medline]
47. Szanto S, Yudkin J: The effect of dietary sucrose on blood lipids, serum insulin, platelet adhesiveness and body weight in human volunteers. Postgrad Med J 45: 602–607, 1969.[Abstract/Free Full Text]
48. Fuh MM-T, Shieh S-M, Wu D-A, Chen Y-DI, Reaven GM: Abnormalities of carbohydrate and lipid metabolism in patients with hypertension. Arch Int Med 147: 1035–1038, 1987.[Abstract/Free Full Text]
49. Reaven GM: Role of insulin resistance in human disease (Banting Lecture 1988). Diabetes 37: 1595–1607, 1988.[Abstract]
50. Reaven GM, Ho H, Hoffman BB. Somatostatin inhibition of fructose-induced hypertension. Hypertension 14: 117–120, 1989.[Abstract/Free Full Text]
51. DeFronzo RA: Insulin and renal sodium handling: clinical implications. Int J Obes 5 (suppl 1): 93–104, 1981.
52. Young JB, Landsberg L: Stimulation of the sympathetic nervous system during sucrose feeding. Nature 269: 615–617, 1977.[Medline]
53. Rowe JW, Young JB, Minaker KL, Stevens AL, Pallotta JA, Landsberg L: Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes 30: 219–225, 1981.[Medline]

This article has been cited by other articles:

				B. V. Howard and J. Wylie-Rosett Sugar and Cardiovascular Disease: A Statement for Healthcare Professionals From the Committee on Nutrition of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association Circulation, July 23, 2002; 106(4): 523 - 527. [Full Text] [PDF]

This Article Abstract Figures Only Full Text (PDF) Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Preuss, H. G. Articles by Knapka, J. Search for Related Content PubMed PubMed Citation Articles by Preuss, H. G. Articles by Knapka, J.