Mechanisms of Altered Contractile Responses to Vasopressin and Endothelin in Canine Coronary Collateral Arteries

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Abstract
Background 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. Methods and Results Contractile responses to vasopressin (100 nmol/L) were enhanced threefold to fourfold in near-resistance (≈200 μm lumen diameter) and conduit (≈500 μm 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 μmol/L), a cyclooxygenase inhibitor, or N G -nitro- l -arginine methyl ester (100 μmol/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 Ca 2+ (measured by use of fura-2 microfluorometry and Ca 2+ -dependent 42 K + efflux) in smooth muscle of collateral arteries than in smooth muscle of noncollateral arteries ( P <.05). Surprisingly, endothelin-induced increases of Ca 2+ were not different in smooth muscle of collateral and noncollateral arteries ( P >.05). Conclusions 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 Ca 2+ 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 Ca 2+ responses of collaterals indicates that the mechanisms involved in increasing Ca 2+ sensitivity of contractile proteins during endothelin stimulation may be altered in collateral arteries.

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