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 ω-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 withl-NAME, switching the bathing solution to physiological saline solution with a reduced Cl− concentration potentiated the contraction. DIDS (5 × 10−6–3 × 10−4 M) caused relaxation of l-NAME-induced tension (IC50 = 55 ± 10 μM), providing evidence for a role of Cl−. SITS (10−5–5 × 10−4 M) did not affectl-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 μM) 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.