COBALT CONTRACTION OF VASCULAR SMOOTH-MUSCLE IS CALCIUM-DEPENDENT

We examined the mechanism by which cobalt causes contraction of vascul ar smooth muscle (VSM), determining whether contractile response of VS M from normotensive and hypertensive rats differed. Contraction of rin gs of rat thoracic aorta from normotensive Wistar-Kyoto rats (WKY) and hypertensive spontaneously hypertensive stroke-prone rats (SHRSP) in response to addition of cobalt chloride to the muscle bath was recorde d. Threshold contraction occurred at 3 mu M; maximum contraction occur red at 100 mu M. There was no difference between rings from WKY and SH RSP in sensitivity or maximum response to cobalt. No contractile respo nse occurred when cobalt was added to a calcium-free physiologic salt solution (PSS) to which 1.0 mM EGTA had been added. When no EGTA was a dded to the PSS, cobalt caused a contraction 20% as great as that obse rved in calcium-containing physiologic salt solution, but this small c ontraction was eliminated after intracellular sequestration of calcium had been prevented by treatment of the rings with cyclopiazonic acid (3 x 10(-4) M). A concentration-dependent contraction occurred when ca lcium was added back to the bath in the presence of cobalt. The contra ction in response to this addition of calcium did not differ between r ings from WKY and SHRSP. Threshold concentrations of cobalt produced m arked potentiations of contractile responses to either norepinephrine (NE) or KCl. We conclude that cobalt causes contraction by activating both voltage-sensitive and receptor-operated calcium channels in the p lasma membrane. Cobalt also caused release of intracellularly sequeste red calcium. There was no difference between the responses to cobalt o f VSM from WKY and SHRSP.