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

AbstractOBJECTIVE:
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
AuthorsC C Juan, V S Fang, Y P Hsu, Y J Huang, D B Hsia, P C Yu, C F Kwok, L T Ho
JournalJournal of hypertension (J Hypertens) Vol. 16 Issue 12 Pt 1 Pg. 1775-82 (Dec 1998) ISSN: 0263-6352 [Print] England
PMID9869011 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Blood Glucose
  • Dietary Carbohydrates
  • Endothelin-1
  • Insulin
  • Oligopeptides
  • Receptor, Endothelin A
  • Receptors, Endothelin
  • BQ 610
  • Fructose
Topics
  • Animals
  • Arteries (chemistry, cytology)
  • Blood Glucose (metabolism)
  • Blood Pressure (drug effects)
  • Dietary Carbohydrates (pharmacology)
  • Disease Models, Animal
  • Endothelin-1 (biosynthesis, blood, genetics)
  • Fructose (pharmacology)
  • Hypertension (chemically induced, metabolism)
  • Insulin (blood)
  • Male
  • Muscle, Smooth, Vascular (cytology, metabolism)
  • Oligopeptides (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Endothelin A
  • Receptors, Endothelin (biosynthesis, genetics)
  • Tail (chemistry, cytology)

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