Mechanisms of altered contractile responses to vasopressin and endothelin in canine coronary collateral arteries.

Abstract

Mature coronary collateral arteries are hyperresponsive to vasopressin; in contrast, contractile responses of collaterals to endothelin are attenuated. Our goal was to determine the cellular mechanisms underlying these differences in reactivity using two sizes of canine collateral arteries isolated from hearts subjected to chronic coronary occlusion. Contractile responses to vasopressin (100 mmol/L) were enhanced threefold to fourfold in near-resistance (approximately 200 microns lumen diameter) and conduit (approximately 500 microns lumen diameter) collateral arteries compared with similarly sized noncollateral coronary arteries (P < .01). In contrast, contractions of both sizes of collaterals in response to endothelin (0.01 to 30 nmol/L) were smaller than responses of size-matched noncollateral arteries (P < .05). Pretreatment with either indomethacin (5 mumol/L), a cyclooxygenase inhibitor, or NG-nitro-L-arginine methyl ester (100 mumol/L), a nitric oxide synthase inhibitor, did not alter the relative responsiveness of collateral arteries to vasopressin or endothelin compared with noncollateral arteries. Vasopressin produced greater increases of intracellular free Ca2+ (measured by use of fura-2 microfluorometry and Ca(2+)-dependent 42K+ efflux) in smooth muscle of collateral arteries than in smooth muscle of noncollateral arteries (P < .05). Surprisingly, endothelin-induced increases of Ca2+ were not different in smooth muscle of collateral and noncollateral arteries (P > .05). We conclude that altered contractile responsiveness of collateral arteries to vasopressin and endothelin does not result from altered synthesis/release of nitric oxide or prostaglandins. Parallel enhancement of vasopressin-mediated Ca2+ and contractile responses suggests increases in vasopressin receptor number, affinity, and/or efficiency of coupling mechanisms in collateral smooth muscle. The dissociation between endothelin-induced contractile and Ca2+ responses of collaterals indicates that the mechanisms involved in increasing Ca2+ sensitivity of contractile proteins during endothelin stimulation may be altered in collateral arteries.