Cardioprotective effects of atrasentan, an endothelin-A receptor antagonist, but not of nitric oxide in diabetic mice with myocyte-specific overexpression of endothelial nitric oxide synthase.

1. We investigated the roles of nitric oxide (NO) and endothelin-1 (ET-1) in organ dysfunction in diabetic mice with normal genotype (wild-type, WT) or myocyte-specific overexpression of endothelial NO synthase (eNOS) (transgenic, TG) after chronic oral treatment with the endothelin-A (ETA) receptor antagonist atrasentan. 2.

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.

Endothelin receptor antagonists: clinical realities and future directions.

Endothelin (ET) is among the strongest endogenous vasoconstrictors known and a potent mitogen. A rich body of experimental evidence suggests that ET contributes to vascular remodeling and end-organ damage in several cardiovascular conditions. Therefore, blockade of ET receptors has been suggested as an attractive target in a number of acute and chronic cardiovascular indications, including pulmonary arterial hypertension (PAH), systemic hypertension, and heart failure.

Influence of acute selective endothelin-receptor-A blockade on renal hemodynamics in a rat model of chronic allograft rejection.

We have recently demonstrated up-regulation of renal endothelin (ET) synthesis in a rat model of chronic renal allograft rejection. Treatment with a selective ET-A receptor antagonist improved survival and reduced functional and morphological kidney damage. However, the underlying mechanisms have not yet been elucidated, as ET exhibits both hemodynamic and inflammatory properties.

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.

Selectivity of different calcium antagonists on T- and L-type calcium currents in guinea-pig ventricular myocytes.

Both L- and T-type calcium channels are present in the heart. In cardiac myocytes L-type calcium channels are blocked by the classical calcium channel blockers, while T-type calcium channels are thought to be insensitive to these drugs and to be selectively blocked by mibefradil. We aimed to compare the T/L calcium channel blocking selectivity of several calcium channel blockers by evaluating their effects on both components evoked in the same cell from a holding potential corresponding to the normal physiological value (-90mV).

Trauma induced by nontraumatic coronary devices and its impact on vascular reactivity and morphology.

This study evaluated the impact of low-pressure balloon devices on coronary morphology and function. An active coronary perfusion catheter (2.5-mm balloon diameter, inflation with 1 bar for 30 min) was placed in the left anterior descending coronary artery of 12 German landrace pigs under general anesthesia.

Endothelin A-receptor antagonist administration immediately after experimental myocardial infarction with reperfusion does not affect scar healing in dogs.

Objective: Endothelin (ET) receptor antagonists have been reported to reduce both infarct size and no-reflow phenomenon; however, in rat models their effect on the healing process after myocardial infarction (MI) is controversial. The study aimed to evaluate the effect of early administration of the ET(A) receptor antagonist darusentan on scar healing in an ischemia-reperfusion model in dogs.

Methods: Thirty male mongrel dogs surviving 180 min left anterior descending coronary artery balloon occlusion were randomised to: darusentan i.