Vascular actions of cicletanine

Vascular wall hypertrophy and enhanced vascular reactivity are characteristic of the hypertensive state. Pharmacologic reversal or prevention of these changes might be of therapeutic benefit. We examined the mechanism by which cicletanine, an antihypertensive vasodilator, induces relaxation of isolated mesenteric resistance arteries and assessed its effects on growth of cultured mesenteric artery myocytes. Initial experiments determined the effect of cicletanine on aortic rings and superior mesenteric arteries isolated from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. Cicletanine induced dose-dependent relaxation of pre-contracted segments of both artery types. Aortas of SHR were more sensitive to cicletanine than those of the WKY, while no difference in sensitivity of mesenteric arteries was observed between the two strains. Within-strain comparisons showed that aortas of SHR were more sensitive to cicletanine than mesenteric arteries while no differences were detected in vessels of the WKY. To assess the mechanism of action, the effect of cicletanine on intracellular Ca2+ was determined in mesenteric resistance arteries loaded with fura-2. In 4 of 4 preparations tested, 100 microM cicletanine induced a rapid fall in the level of free ionized Ca2+. When the endothelial lining of superior mesenteric arteries was removed or vessels were pre-treated with either 1 microM propranolol, 0.1 mM ouabain or 5 microM indomethacin, no effect on cicletanine-induced relaxation (10-300 microM) was detected.(ABSTRACT TRUNCATED AT 250 WORDS)