Vasodilator responses to acetylcholine, bradykinin, and substance P are mediated by a TEA-sensitive mechanism.

The effects of tetraethylammonium (TEA), a K+ channel antagonist, on vasodilator responses were investigated in the hindquarters vascular bed of the cat under constant-flow conditions. After administration of TEA in a total dose of 60 mg/kg into the hindquarters perfusion circuit, vasodilator responses to acetylcholine, bradykinin, and substance P were reduced, whereas vasodilator responses to the NO donors, diethylamine-NO complex, S-nitroso-N-acetylpenicillamine, and sodium nitroprusside, and to prostaglandin E1, albuterol, vasoactive intestinal polypeptide, isradipine, and levcromakalim were not altered. The inhibitory effect of TEA on responses to the endothelium-dependent vasodilators was reversible with time, and vasoconstrictor responses to norepinephrine, U-46619, angiotensin II, and BAY K 8644 were enhanced by the K+ channel antagonist. Although TEA had no sustained effect on baseline systemic arterial and hindquarters perfusion pressures, the NO synthase inhibitor, N omega-nitro-L-arginine methyl ester, increased these pressures in the presence of TEA. The results of the present investigation suggest that TEA attenuates vasodilator responses to acetylcholine, bradykinin, and substance P by inhibiting the release of endothelium-derived relaxing factor. These data suggest that the acetylcholine-, bradykinin-, and substance P-stimulated release of endothelium-derived relaxing factor may involve the opening of a TEA-sensitive K+ channel in the endothelium in the hindlimb vascular bed of the cat, but that a TEA-sensitive mechanism is not involved in the maintenance of baseline tone in this vascular bed.