Effects of chronic endothelin ET(A) receptor blockade on blood pressure and vascular formation of cyclic guanosine-3',5'-monophosphate in spontaneously hypertensive rats.

Endothelin (ET) mediates vasoconstriction in intact arterial blood vessels with functional endothelium via stimulation of ET(A) receptors, while ET(B) receptor stimulation leads to vasodilation via nitric oxide (NO) release and formation of cyclic guanosine-3',5'-monophosphate (cGMP). In spontaneously hypertensive rats (SHR) the cGMP-forming NO-receptor guanylyl cyclase (sGC) is downregulated. It is unclear whether ET contributes to the hypertensive phenotype of SHR, and whether this involves the disturbed cGMP signaling.

Effects of the endothelin a receptor antagonist darusentan on blood pressure and vascular contractility in type 2 diabetic Goto-Kakizaki rats.

The present study evaluated the effects of long-term treatment with the endothelin A (ET(A)) receptor antagonist darusentan (LU135252) on blood pressure (BP) and vascular target-organ damage in spontaneously type 2 diabetic Goto-Kakizaki (GK) rats. BP was monitored by radiotelemetry in untreated and darusentan-treated GK rats from 10-24 weeks of age. Relaxation of mesenteric artery segments by acetylcholine (ACh) and sodium nitroprusside (SNP) was measured to assess endothelium-dependent and -independent vasorelaxation.