PMID: 8594911Dec 1, 1995Paper

Effect of chronic endothelin blockade in hyperinsulinemic hypertensive rats

The American Journal of Physiology
S VermaJohn H McNeill

Abstract

Evidence suggests that hyperinsulinemia may be causally related to the development of high blood pressure (BP) in fructose-hypertensive (FH) rats. Because plasma insulin has been shown to modulate endothelin (ET) release in vivo, we hypothesized that hyperinsulinemia may provide a continual stimulus for ET release, which could increase BP by altering plasma or blood vessel ET levels. To test this hypothesis, we studied the effect of chronic ET-receptor blockade (by using bosentan, a noncompetitive ET antagonist) on plasma insulin levels, plasma ET levels, blood vessel ET content, and BP in FH rats. Chronic oral bosentan treatment (100 mg.kg-1.day-1) was initiated in 6-wk-old Sprague-Dawley rats. One week after bosentan treatment was started, rats were fed either normal rat chow or a fructose-enriched diet. Plasma insulin, plasma glucose, and systolic BP were measured weekly. At termination (in 15-wk-old rats), plasma ET levels and total mesenteric ET content were determined. Bosentan treatment caused a sustained decrease in BP in the FH rats (treated 130 +/- 4 vs. untreated 149 +/- 2 mmHg, P < 0.001) but had no effect in the normotensive control group. FH rats had a higher total mesenteric ET content compared with the control g...Continue Reading

Citations

Oct 26, 2000·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·G A ReinhartB F Cox
Jul 19, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Denise M GalipeauJohn H McNeill
Feb 13, 2001·American Journal of Physiology. Heart and Circulatory Physiology·P V KatakamA W Miller
Jul 1, 2004·American Journal of Physiology. Endocrinology and Metabolism·Chi-Chang JuanLow-Tone Ho
Nov 13, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Denise GalipeauJohn H McNeill

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