INVOLVEMENT OF NITRIC-OXIDE AND POTASSIUM CHANNELS IN THE REDUCTION OF BASAL TONE PRODUCED BY BLOCKADE OF THROMBOXANE A(2) PROSTAGLANDIN H-2 RECEPTORS IN AORTIC RINGS OF HYPERTENSIVE RATS/

This study was designed to investigate involvement of potassium channe ls in the action of nitric oxide facilitating reduction of basal tone by thromboxane A(2)/prostaglandin H-2 receptor blockade with ifetroban in rings of thoracic aorta taken from rats with aortic coarctation-in duced hypertension. Ifetroban-induced reduction of basal tone in aorti c rings without drug pretreatment was attenuated (P<0.05) in rings pre treated with the nitric oxide synthesis inhibitor N omega-nitro-L-argi nine methyl ester (L-NAME; 3 x 10(-4) mol/L; 0.55+/-0.09 g versus 0.23 +/-0.07 g). The vasorelaxing effect of ifetroban also was decreased (P <0.05) in preparations pretreated with a potassium channel blocker, ei ther tetraethylammonium (TEA; 10(-2) mol/L) or 4-aminopyridine (4-AP; 3 x 10(-3) mol/L). Ifetroban-induced reduction of basal tone was not a ttenuated in preparations pretreated first with L-NAME and then with s odium nitroprusside (SNP; 6+/-1 nmol/L) to compensate for the loss of endogenous nitric oxide. However, the facilitatory effect of SNP on if etroban-induced relaxation of aortic rings pretreated with L-NAME alon e was not demonstrable in rings pretreated with L-NAME plus TEA or 4-A P. These observations suggest that a mechanism involving nitric oxide and potassium channels facilitates the reduction in basal tone produce d by ifetroban in aortic rings of rats with aortic coarctation-induced hypertension.