VASORELAXANT PROPERTIES OF NORBORMIDE, A SELECTIVE VASOCONSTRICTOR AGENT FOR THE RAT MICROVASCULATURE

1 The effects of norbormide on the contractility of endothelium-depriv ed rat, guinea-pig, mouse, and human artery rings, and of freshly isol ated smooth muscle cells of rat caudal artery were investigated. In ad dition, the effect of norbormide on intracellular calcium levels of A7 r5 cells was evaluated. 2 In resting rat mesenteric, renal, and caudal arteries, norbormide (0.5-50 mu M) induced a concentration-dependent contractile effect. In rat caudal artery, the contraction was very slo wly reversible on washing, completely abolished in the absence of extr acellular calcium, and antagonized by high concentrations (10-800 mu M ) of verapamil. The norbormide effect persisted upon removal of either extracellular Na+ or K+. The contractile effect of norbormide was obs erved also in single, freshly isolated smooth muscle cells from rat ca udal artery. 3 In resting rat and guinea-pig aortae, guinea-pig mesent eric artery, mouse caudal artery, and human subcutaneous resistance ar teries, norbormide did not induce contraction. When these vessels were contracted by 80 mM KCl, norbormide (10-100 mu M) caused relaxation. Norbormide inhibited the response to Ca2+ of rat aorta incubated in 80 mM KCl/Ca2+-free medium. Norbormide (up to 100 mu M) was ineffective in phenylephrine-contracted guinea-pig and rat aorta. 4 In A7r5 cells, a cell line from rat aorta, norbormide prevented high K+- but not 5-h ydroxytryptamine-induced intracellular calcium transients. 5 These fin dings indicate that in vitro, norbormide induces a myogenic contractio n, selective for the rat small vessels, by promoting calcium entry in smooth muscle cells, presumably through calcium channels. In rat aorta and arteries from other mammals, norbormide behaves like a calcium ch annel entry blocker.