Development of Endothelium-Dependent Relaxation in Canine Coronary Collateral Arteries

Abstract

Background —Little information exists regarding development of vasomotor control mechanisms during coronary collateral artery maturation. Therefore, we studied endothelium-dependent relaxation of canine collateral arteries isolated 2, 4, and 9 months after placement of an ameroid occluder around the proximal left circumflex coronary artery. Results —Collateral arteries isolated after 2 months exhibited markedly reduced endothelium-dependent relaxation in response to acetylcholine (ACh; 10 −10 to 10 −4 mol/L) and bradykinin (BK; 10 −11 to 10 −6 mol/L) compared with relaxation of noncollateral coronary arteries ( P <0.01). In contrast, endothelium-independent relaxation of collateral arteries to nitroprusside was only slightly reduced compared with relaxation of noncollateral arteries ( P <0.05). Endothelium-dependent relaxation of collateral arteries isolated after 4 and 9 months was increased significantly, to the extent that relaxation to ACh and BK was not significantly different between collateral and noncollateral arteries at these periods. Inhibition of nitric oxide synthesis with N Τ -nitro- l -arginine methyl ester (L-NAME; 100 μmol/L) markedly inhibited ACh-induced relaxation in all noncollateral arteries and in collateral arteries isolated after 9 months. However, neither L-NAME nor indomethacin (5 μmol/L) alone inhibited ACh-mediated relaxation of collateral arteries isolated after 4 months. ACh-induced relaxation of these collateral arteries was only inhibited when arteries were preconstricted with 30 mmol/L K + and pretreated with L-NAME and indomethacin (ie, when synthesis/effects of nitric oxide, prostaglandins, and endothelium-derived hyperpolarizing factor were inhibited). Conclusions —Development of endothelium-dependent relaxation in canine coronary collateral arteries is not complete after 2 months. After 4 months, endothelium-dependent relaxation of collateral arteries is similar to relaxation of noncollateral arteries, but the relaxation exhibits decreased dependence on synthesis of nitric oxide and increased involvement of prostaglandins and endothelium-derived hyperpolarizing factor(s). After 9 months of development, collateral arteries exhibit normal nitric oxide–dependent relaxation, similar to noncollateral arteries.