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Am J Physiol Heart Circ Physiol 279: H2604-H2611, 2000;
0363-6135/00 $5.00
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Vol. 279, Issue 6, H2604-H2611, December 2000

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

Jonathan E. Graves, Iain A. Greenwood, and William A. Large

Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London SW17 ORE, United Kingdom

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 Nomega -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 × 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 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 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.

chloride channel; vascular smooth muscle


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