Overexpression of vascular endothelin-1 and endothelin-A receptors in a fructose-induced hypertensive rat model

J Hypertens. 1998 Dec;16(12 Pt 1):1775-82. doi: 10.1097/00004872-199816120-00010.

Abstract

Objective: To examine the temporal relationship between hyperinsulinemia and hypertension in the fructose-hypertensive rat model and to study the function of endothelin-1 (ET-1) in fructose-induced hypertension.

Design: Since ET-1 induces insulin resistance in conscious rats, we tested the hypothesis that both hyperinsulinemia and hypertension developed in the fructose-hypertensive rat model might be the sequelae of an elevated tissue content of ET-1 and ET(A) receptors.

Materials and methods: Systolic hypertension was induced within 3 weeks in male Sprague-Dawley rats fed on a fructose-rich diet. After continual monitoring of blood pressure and plasma insulin concentrations, the animals were killed at the end of experiment to determine plasma levels of ET-1, the contractile response of aortic rings to ET-1, and ET-1 and ET(A) receptor gene expressions. In a separate experiment, BQ-610 was administered to lower the effect of ET-1 in rats with fructose-induced hypertension.

Results: Compared with control rats given normal chow, the fructose-fed rats developed systolic hypertension after 3 weeks of the diet (127+/-3.7 versus 110+/-5.5 mmHg, P < 0.01) and hyperinsulinemia both before (1 07.1+/-32.5 versus 48.5+/-14.3 pmol/l, P < 0.005) and after (96.6+/-63.7 versus 50.4+/-5.6 pmol/l, P< 0.05) they became hypertensive. Although plasma ET-1 levels did not differ between the rat groups, aortic ring contraction-concentration curves, indicating vessel contractility in response to ET-1, were significantly greater in these rats than in controls (F1,72 = 12.34, P< 0.00077). Messenger RNA extracted from the tail arteries and blotted with both ET-1 and ET(A) probes showed that fructose-fed rats had greater ET-1 and ET(A)-receptor gene expression than control rats. Concomitant administration of BQ-610 to rats fed on a fructose diet significantly reduced the hypertension. Conclusions These findings suggest that elevated vascular expression of ET-1 and ET(A) receptor genes may mediate the development of hypertension and hyperinsulinemia in rats fed a fructose-rich diet

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteries / chemistry
  • Arteries / cytology
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects
  • Dietary Carbohydrates / pharmacology
  • Disease Models, Animal
  • Endothelin-1 / biosynthesis*
  • Endothelin-1 / blood
  • Endothelin-1 / genetics
  • Fructose / pharmacology*
  • Hypertension / chemically induced*
  • Hypertension / metabolism*
  • Insulin / blood
  • Male
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / metabolism
  • Oligopeptides / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Endothelin A
  • Receptors, Endothelin / biosynthesis*
  • Receptors, Endothelin / genetics
  • Tail / chemistry
  • Tail / cytology

Substances

  • Blood Glucose
  • Dietary Carbohydrates
  • Endothelin-1
  • Insulin
  • Oligopeptides
  • Receptor, Endothelin A
  • Receptors, Endothelin
  • BQ 610
  • Fructose