MECHANISMS OF ALTERED CONTRACTILE RESPONSES TO VASOPRESSIN AND ENDOTHELIN IN CANINE CORONARY COLLATERAL ARTERIES

Background Mature coronary collateral arteries are hyperresponsive to vasopressin; in contrast, contractile responses of collaterals to endo thelin are attenuated. Our goal was to determine the cellular mechanis ms underlying these differences in reactivity using two sizes of canin e collateral arteries isolated from hearts subjected to chronic corona ry occlusion. Methods and Results Contractile responses to vasopressin (100 nmol/L) were enhanced threefold to fourfold in near-resistance ( approximate to 200 mu m lumen diameter) and conduit (approximate to 50 0 mu m lumen diameter) collateral arteries compared with similarly siz ed noncollateral coronary arteries (P<.01). In contrast, contractions of both sizes of collaterals in response to endothelin (0.01 to 30 nmo l/L) were smaller than responses of size-matched noncollateral arterie s (P<.05). Pretreatment with either indomethacin (5 mu mol/L), a cyclo oxygenase inhibitor, or N-G-nitro-L-arginine methyl ester (100 mu mol/ L), a nitric oxide synthase inhibitor, did not alter the relative resp onsiveness of collateral arteries to vasopressin or endothelin compare d with noncollateral arteries. Vasopressin produced greater increases of intracellular free Ca2+ (measured by use of fura-2 microfluorometry and Ca2+-dependent K-42(+) efflux) in smooth muscle of collateral art eries than in smooth muscle of noncollateral arteries (P<.05). Surpris ingly, endothelin-induced increases of Ca2+ were not different in smoo th muscle of collateral and noncollateral arteries (P>.05). Conclusion s We conclude that altered contractile responsiveness of collateral ar teries to vasopressin and endothelin does not result from altered synt hesis/release of nitric oxide or prostaglandins. Parallel enhancement of vasopressin-mediated Ca2+ and contractile responses suggests increa ses in vasopressin receptor number, affinity, and/or efficiency of cou pling mechanisms in collateral smooth muscle. The dissociation between endothelin-induced contractile and Ca2+ responses of collaterals indi cates that the mechanisms involved in increasing Ca2+ sensitivity of c ontractile proteins during endothelin stimulation may be altered in co llateral arteries.