Carbon monoxide produced by isolated arterioles attenuates pressure-induced vasoconstriction

Studies were conducted on isolated rat gracilis muscle arterioles to examin e the role of vascular heme oxygenase (HO)- derived carbon monoxide (CO) on myogenic constrictor responses to stepwise increments in intraluminal pres sure. The arterioles express HO-2 but not HO-1 and manufacture CO. Both HO- 2 protein expression and CO production are reduced in arterioles maintained for 18 h before experimentation in media containing HO-2 antisense oligode oxynucleotides (AS-ODN). Pressurization of arterioles mounted on a myograph over the pressure range of 40-100 mmHg elicits reduction of internal diame ter. At pressures >40 mmHg, the internal diameter of vessels treated with e ither HO-2 AS-ODN, the HO inhibitor chromium mesoporphyrin (CrMP), or the K + channel blocker tetraethylammonium (TEA) are smaller than the correspondi ng control values. The inclusion of exogenous CO, but not of biliverdin, in the superfusion buffer attenuates pressure-induced vasoconstriction in CrM P-treated vessels. However, exogenous CO does not attenuate pressure-induce d vasoconstriction in vessels treated with both CrMP and TEA. Collectively, these data suggest that CO of vascular origin attenuates pressure-induced arteriolar constriction via a mechanism involving a TEA-sensitive K+ channe l.