The effects of SIN-1 were investigated on the electrical and mechanical properties of vascular smooth muscle cells of the canine saphenous vein. Isolated tissues with or without endothelium were contracted with norepinephrine, prostaglandin F2 alpha or endothelin. SIN-1 and nitric oxide caused comparable concentration-dependent relaxations in rings with and without endothelium irrespective of the contracting agent. The relaxations to both SIN-1 and nitric oxide were inhibited by methylene blue. SIN-1 (up to 10(-5) M) and nitric oxide (up to 10(-5) M) did not alter membrane potential. The excitatory junction potentials and the slow depolarization generated by perivascular nerve stimulation were not affected by SIN-1 or nitric oxide. These results suggest that SIN-1 relaxes vascular smooth muscle by increasing the production of cyclic GMP without changing the membrane potential. In addition, SIN-1 does not modify peripheral adrenergic neurotransmission.