title: Involvement of nitric oxide and potassium channels in the reduction of basal tone produced by blockade of thromboxane A2/prostaglandin H2 receptors in aortic rings of hypertensive rats.
abstract: This study was designed to investigate involvement of potassium channels in the action of nitric oxide facilitating reduction of basal tone by thromboxane A2/prostaglandin H2 receptor blockade with ifetroban in rings of thoracic aorta taken from rats with aortic coarctation-induced hypertension. Ifetroban-induced reduction of basal tone in aortic rings without drug pretreatment was attenuated (P<0.05) in rings pretreated with the nitric oxide synthesis inhibitor N(omega-nitro-L-arginine 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, either 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 attenuated in preparations pretreated first with L-NAME and then with sodium nitroprusside (SNP; 6+/-1 nmol/L) to compensate for the loss of endogenous nitric oxide. However, the facilitatory effect of SNP on ifetroban-induced relaxation of aortic rings pretreated with L-NAME alone was not demonstrable in rings pretreated with L-NAME plus TEA or 4-AP. These observations suggest that a mechanism involving nitric oxide and potassium channels facilitates the reduction in basal tone produced by ifetroban in aortic rings of rats with aortic coarctation-induced hypertension.
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla, 10595, USA.
authors.forename: A
authors.initials: A
authors.lastname: DelliPizzi
authors.forename: A
authors.initials: A
authors.lastname: Nasjletti
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001481:Basal Metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D009129:Muscle Tonus / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010080:Oxazoles / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D019789:Tetraethylammonium / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D010080:Oxazoles; D015221:Potassium Channels; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019789:Tetraethylammonium; D015761:4-Aminopyridine; C078904:ifetroban; D019331:NG-Nitroarginine Methyl Ester