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 nitric oxide (NO), using infusion of either NO donor sodium nitroprusside (SNP) or S-nitroso-acetyl-DL-penicillamine (SNAP) on mean arterial pressure (MAP) responses to vasoconstrictors (phenylephrine, angiotensins I and II) and 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, angiotensin I, and angiotensin II were reduced by 40 to 80%, whereas the responses to bradykinin or acetylcholine were enhanced by 50 to 80%. These changes in vascular responsiveness persisted for at least 24 h after the SNP infusion. Pretreatment with either tetraethylammonium (360 micromol/kg) or 4-aminopyridine (4-AP; 1 micromol/kg) did not alter the effects of phenylephrine or bradykinin in control animals, but prevented SNP-induced changes in responsiveness to phenylephrine or bradykinin. On the other hand, administration of tetraethylammonium, even 24 h after SNP infusion, reversed hyporesponsiveness to phenylephrine, whereas 4-AP was ineffective. Tetraethylammonium and 4-AP did not alter the increased responses to bradykinin. Glibenclamide was without effect in any situation. These results indicate that NO-induced changes 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 activation of a tetraethylammonium-sensitive population of K+ channels.
Eduardo da Silva-Santos
J
J
Department of Pharmacology, Universidade Federal de Santa Catarina, SC, Brazil.
Assreuy
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D008297:Male; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology*; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D010396:Penicillamine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D020030:Nitric Oxide Donors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine