Long-lasting changes of rat blood pressure to vasoconstrictors and vasodilators induced by nitric oxide donor infusion: Involvement of potassium channels

We investigated the effects of the exposure of the rat vascular system to n itric oxide (NO), using infusion of either NO donor sodium nitroprusside (S NP) or S-nitroso-acetyl-DL-penicillamine (SNAP) on mean arterial pressure ( MAP) responses to vasoconstrictors (phenylephrine, angiotensins I and ii) a nd to vasodilators (bradykinin, acetylcholine, SNP, and iloprost). SNP (250 nmol/kg/min) or SNAP (85 nmol/kg/min) infused for 30 min decreased MAP by 40 to 60 mm Hg. MAP returned to normal levels 5 to 10 min after the end of infusion. After infusion of SNP or SNAP the effects of phenylephrine, angio tensin I, and angiotensin II were reduced by 40 to 80%, whereas the respons es to bradykinin or acetylcholine were enhanced by 50 to 80%. These changes in vascular responsiveness persisted for at least 24 h after the SNP infus ion. Pretreatment with either tetraethylammonium (360 mu mol/kg) or 4-amino pyridine (4-AP; 1 mu mol/kg) did not alter the effects of phenylephrine or bradykinin in control animals, but prevented SNP-induced changes in respons iveness to phenylephrine or bradykinin. On the other hand, administration o f tetraethylammonium, even 24 h after SNP infusion, reversed hyporesponsive ness to phenylephrine, whereas 4-AP was ineffective. Tetraethylammonium and 4-AP did not alter the increased responses to bradykinin. Glibenclamide wa s without effect in any situation. These results indicate that NO-induced c hanges on vascular responsiveness to vasoconstrictors and vasodilators are much more profound and long-lasting than described previously and that the effects of NO appear to be, at least in part, mediated by persistent activa tion of a tetraethylammonium-sensitive population of K+ channels.