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


METHODS
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.


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
Juan
C C
CC
Department of Physiology, National Yang-Ming University, Veterans General Hospital-Taipei, Taiwan, Republic of China.
Fang
V S
VS
Hsu
Y P
YP
Huang
Y J
YJ
Hsia
D B
DB
Yu
P C
PC
Kwok
C F
CF
Ho
L T
LT
D000818:Animals; D001158:Arteries / Q000737:chemistry / Q000166:cytology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004040:Dietary Carbohydrates / Q000494:pharmacology; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D005632:Fructose / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000096:biosynthesis* / Q000235:genetics; D013623:Tail / Q000737:chemistry / Q000166:cytology
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D019332:Endothelin-1; D007328:Insulin; D009842:Oligopeptides; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; C087220:BQ 610; D005632:Fructose