Antihypertensive Effects of a Soluble Guanylate Cyclase Stimulator.

ABSTRACT

We studied antihypertensive activity of an indolinone derivative (compound GRS), a soluble guanylate cyclase stimulator and a drug with previously proven antiaggregant effects. Contraction activity of isolated aorta segments of Wistar-Kyoto (WKY) rats was assessed in vitro using a mechanographic method. Addition of GRS (0.1-100 µÐœ) resulted in dose-dependent relaxation of endothelium-denuded aorta segments. Pretreatment of aorta smooth muscle segments with a specific inhibitor of soluble guanylate cyclase (ODQ, 1 µM) weakened the vasodilatory effect of GRS. Antihypertensive activity of the indolinone derivative GRS was studied in spontaneously hypertensive SHR rats. Single oral administration of 5 and 10 mg/kg GRS was followed by a significant dose-dependent reduction of systolic and diastolic BP in SHR rats. Antihypertensive effect of GRS in a dose of 5 mg/kg was more potent than that of the reference drug isosorbide dinitrate. GRS in a dose of 10 mg/kg did not affect systolic and diastolic BP in normotensive WKY rats.