Cobalt contraction of vascular smooth muscle is calcium dependent.
We examined the mechanism by which cobalt causes contraction of vascular smooth muscle (VSM), determining whether contractile response of VSM from normotensive and hypertensive rats differed. Contraction of rings 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 recorded. Threshold contraction occurred at 3 microM; maximum contraction occurred at 100 microM. There was no difference between rings from WKY and SHRSP in sensitivity or maximum response to cobalt. No contractile response 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 added to the PSS, cobalt caused a contraction 20% as great as that observed in calcium-containing physiologic salt solution, but this small contraction 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 calcium was added back to the bath in the presence of cobalt. The contraction in response to this addition of calcium did not differ between rings from WKY and SHRSP. Threshold concentrations of cobalt produced marked 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 plasma membrane. Cobalt also caused release of intracellularly sequestered calcium. There was no difference between the responses to cobalt of VSM from WKY and SHRSP.
Gallagher
M J
MJ
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622.
Alade
P I
PI
Dominiczak
A F
AF
Bohr
D F
DF
D000818:Animals; D002118:Calcium / Q000502:physiology*; D003035:Cobalt / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects*
D003035:Cobalt; D004533:Egtazic Acid; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine