Effects of antihypertensive drugs on metabolic alterations in the fructose-induced hypertension

ATH-APRIL 1995-VOL.8, NO.4,PART 2

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HYPERINSULINEMIA INDUCES VASCULAR WALL THICKNESS IN SHR & WKY RATS INDEPENDENTLY OF BLOOD PRESSURE CHANGE. R Zimlichman*. L Zeidel. J Barg, D Gcfel. Z Matas. S Gass. C Shahar, Y Nakash, HE Eliahou. Depts of Medicine & Hypertension. Tel-Aviv Univ. Wolfson Med Ctr, Holon. 58100. Israel. To evaluate the effect of hyperinsulinemia on vascular wall, insulin retard o.au/K/d was given for 3 wks intraperitoneally(ip) to SHR & WKY rats. 10~ sucrose solution was given to drink to avoid hypoglycemia. 8% salt was ddded to chow to investigate its effect on BP. At the end of 3 wks the hearts were weighed, fixed in formaldehyde and stained with H & E. Wall thickness of 100-u arterioles were measured & factored with diameter. An average of 3 vessels :In each rat, carried out in a blinded manner. is presented. A significant increase in arteriolar wall thickness wall found in both SHR & WKY rats. despite that hyperinsulinemia increased BP in SHR but not in WKY. Syst DP Wall thick/diam Initial After 3 wks WKY placebo 126±7 129±23 O.262±0.08 WKY insulin 141±18 151±7.4 0.342±0.07* SHR placebo 203±16 242±14 O.337±0.07 SHR insulin 202±13 239±18* O.384±O.04** * p.O.OJ7 VB WKY plac; ** p-O.0051 vs SHR plac Heart weights/total body weights in placebo did not differ from insulin groups. Conclusion: Hyperinsulinemia caused an increase in myocardial capillary wall thickness in Loth SHR & WKY independent of DP changes &before the appearance of significant increase in heart weights. It is therefore suggested that insulin may have an etiologic role in arteriolar wall thickness and may participate in acceleration of atherogenesis. KeyWords:

INSULIN INDUCES HYPERTROPHY OF CARDIOMYOCYTES AND PROLIFERATION OF NONCARDIOMYOCYTES IN CULTURE. R Zimlichman*. H Eliahou. S Gass. Z Vogel. D Gefel J Barg. Depts of Medicine & Hypert, Tel-Aviv Univ, Wolfson Med Ctr. Holon. 58100. Israel. The embryonal environmental milieu has been shown to induce myocardial changes in rat offspring. Little is known about the effect of hyperinsulinemia on the development of cardiomyocytes in culture. 2-dsy old cardiomyocyte(postnatal day 1) from WKY & SHR were exposed to concentrations of insulin & spontaneous contractile activity was measur~d. There was a significant difference between the 2 cultures with regards to the rate of contractions of cardiomyocytes. In SHR their spont aneous contractionswere 181±6 & in WKY 129tlO!min. A 20% decreas~ in contractions was evident after 20 min with 10nM insulin in sHR cultures whereas in WKY only minor fluctuations were observed. The effect of insulin on cardiomyocyte growth was monitored in 5- & 7-day old cultures. No significant difference in the ab..~ of cardiomyocytes was observed between the 2 groups under control conditions. but insulin induced a significant incr~ase (35%) in cardiomyocyte size. Insulin accelerated the increasp. in the number of noncardiomyocyte cells in WKY from 32% to 44% & in the SHR from 36% to 58%. These findings show that SHR cardiomyocytes differ from those of WKY in the early stages of development. Insulin caused hypertrophy of cardiomyocytes as well as an increase in the number of noncardiomyocytes in both WKY &SHR cardiac cell cultures.

Insulin. Atherogenesis. Rats. Vascular wall.

Cardiomyocytea. Insulin. Hypertrophy. Rats

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ACARBOSE IMPROVES INSULIN SENSITIVITY AND REDUCES BLOOD PRESSURE IN SUCROSEINDUCED HYPERTENSION INRATS. R..Zimlichman·, E Cohea-Melamed, and Z Madar. Dept. of Biochemistry, Nutrition, Hebrew University, Rehovot, and Dept. of

EFFECTS OF ANTIHYPERTENSIVE DRUGS ON ~ETABOLIC ALTERATIONS IN THE FRUCTOSE-INDUCED HYPERTENSION. J Navarro, V Barrios, R Maeso, E Rodrigo, R Murioz, V Cachofeiro, LM Ruilope~ Y:...l.!!J.lc!. Department of Physiology. Complutense University, Madrid (Spainl

Medicine and Hypertension, Wolfson Medical Center, Tel Aviv University, ISRAEL. Hypertension is often associated with impaired glucose tolerance and high insulin levels. The present study evaluates the effect of acarbose • a hypoglycemic drug that inhibits carbohydrate digestion in sucrose-induced hypertension in rats. Effects of diets fed to three groups of rats for a 16 week period were studied: sucrose + NaCI (1%, w/v) with or without acarbose (0.04%, w/w) and a third of carbohydrates. Acarbose significantly decreased body weight and fasting glucose levels. Postprandial glucose and insulin levels were attenuated in rates fed sucrose + acarbose. Systolic blood pressure significantly increased from (p
Fructose feeding induces a moderate increase in blood pressure levels in normal rats which is associated with insulin reslstance, hyperinsulinemia and dislipidemia. This model reproduces experimentally some of ths Characteristics of the human metabolic syndrome X. The administration of clonidineto fructose-fed rats prevents hypertension, suggesting a rolo of the sympathetic nervous sistem in the pathogenesis of this model. However, it is not known if treatments with antihypertensive drugs, such as ACE inhibitors or celciem-antascnlsts are able to affect the pressor andlor metabolic alterations in this model. Sprague-Dawley rats (150 g) were fed for 4 weeks with diets containing 60% of fructose IF) or 60% of starch (control, CIand received Quinapril (a, 10 mg/kg/dayl or Diltiazem (0, 75 mglkg/day) in the drinking water. Basally and at the end of the study, systolic blood pressure (SBP), renal excretory function and plasma revels of glucose, insulin and triglyceride were determined. At the end of the study a glucose tolerante test (1.5 g) was performed, and plasma samples were obtained basally and 15, 30, 60 and 90 minutes after glucose administration. Group F showed higher SBP compared to group C (125 ± 2 vs 102 ± 3 mmHg; p