Tonic regulation of vascular tone by nitric oxide and chloride ions in rat isolated small coronary arteries

We have investigated the involvement of Cl- in regulating vascular tone in rat isolated coronary arteries mounted on a small vessel myograph. Mechanical removal of the endothelium or inhibition of nitric oxide (NO) synthase with N-omega-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) led to contraction of rat coronary arteries, and these contractions were sensitive to nicardipine (10(-6) M). This suggests that release of NO tonically inhibits a contractile mechanism that involves voltage-dependent Ca2+ channels. In arteries contracted with L-NAME, switching the bathing solution to physiological saline solution with a reduced Cl- concentration potentiated the contraction. DIDS (5 x 10(-6) -3 x 10(-4) M) caused relaxation of L-NAME-induced tension (IC50 = 55 +/- 10 mM), providing evidence for a role of Cl-. SITS (10(-5) -5 x 10(-4) M) did not affect L-NAME-induced tension, suggesting that DIDS is not acting by inhibition of anion exchange. Mechanical removal of the endothelium led to contraction of arteries, which was sensitive to DIDS (IC50 = 50 +/- 8 muM) and was not affected by SITS. This study suggests that, in rat coronary arteries, NO tonically suppresses a contractile mechanism that involves a Cl- conductance.