PMID: 2124474Jul 1, 1990Paper

Cicletanine avoids the proliferation of vascular smooth muscle in the spontaneously hypertensive rat

Archives des maladies du coeur et des vaisseaux
R D Bukoski

Abstract

The vasodilator and antiproliferative effects of the antihypertensive agent, cicletanine, were studied on mesenteric arteries (MA) and cultured mesenteric artery myocytes derived from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. Cicletanine induces relaxation of precontracted MA with an 1050 value of approximately 30-50 microM. Cicletanine inhibits the proliferation of cultured myocytes (passage 5) with an 1050 of 440 +/- 24 microM for SHR and 517 +/- 12 microM for WKY, p less than 0.05, indicating that a log-unit shift in sensitivity exists between its vasodilator and antiproliferative actions. Preliminary experiments suggest that the antiproliferative action of cicletanine is accompanied by an inhibition of DNA synthesis [( 3H] - thymidine uptake) in myocytes of SHR and a stimulation of DNA synthesis in myocytes of the WKY. Cicletanine also lowers free intracellular Ca2+ (determined using fura-2) in myocytes of SHR but not the WKY. In other cell systems, cicletanine has been shown to stimulate prostacyclin production. However, in the present experiments, inhibition of the cyclooxygenase pathway (5 microM indomethacin) attenuated the antiproliferative action of cicletanine by only 30% in cells of ...Continue Reading

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