K⁺ Channels Underlie Conducted Vasodilation in Human Coronary Arterioles

Bradykinin is known to have a powerful hypotensive effect. Antihypertensive ACE inhibitors reduce angiotensin II conversion and slow down bradykinin degradation. In human small coronary arteries, bradykinin causes endothelium-dependent vasodilation by stimulating pathways linked to increases in endothelial cell Ca²⁺. Here we show that hyperpolarization underpins most of the dilation.

Arterioles obtained from samples of right atrial appendage from patients undergoing cardiopulmonary bypass surgery were isolated, cannulated and pressurized to 80 mmHg. Myogenic tone (mean near 20%) developed in more than 50% of arteries. From this tone, bradykinin evoked reversible vasodilation, which was only partially sensitive to block of nitric oxide synthase, and further blocked by inhibitors of Ca²⁺-activated K⁺ channels (K_Ca).

By using a pipette to pump a mixture of bradykinin (10 µM) and a fluorescent marker dye, the delivery of bradykinin was confirmed to the downstream end of cannulated arteries. Both local and conducted vasodilation was observed, which did not decay through at least 1000 µm upstream from the delivery site. Conducted vasodilation was reduced by blockers of K_Ca channels, and was completely inhibited by increasing extracellular [K⁺] up to 45 mM. These data demonstrate a prominent role for endothelium-dependent hyperpolarization in the initiation of conducted vasodilation in human small coronary arteries.