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.
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.
DelliPizzi
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Department of Pharmacology, New York Medical College, Valhalla, 10595, USA.
Nasjletti
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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
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