Potassium channels are not involved in vasopressin-induced vasodilation in the rat lung.
We have previously observed that arginine vasopressin (AVP)-induced pulmonary vasodilation is attenuated by nitric oxide (NO) synthesis inhibition; however, blockade of the response is incomplete even at very high doses of the inhibitor. Thus it was hypothesized that the remaining vasodilation might be due to release of an endothelium-derived hyperpolarizing factor acting to open vascular smooth muscle K+ channels. Lungs were isolated from male Sprague-Dawley rats and perfused at constant flow with physiological saline solution containing 4% albumin. After equilibration, lungs were treated with either glibenclamide (50 microM), Ba2+ (100 microM), tetraethylammonium (10 mM), or the respective vehicle and were then constricted with the thromboxane mimetic U-46619. Upon development of a stable degree of vasoconstriction, AVP (2.5 x 10(-9) M) was administered and its vasodilator action noted. AVP caused an approximately 60% reversal of U-46619 vasoconstriction in control lungs, and this response was not affected by any of the K+ channel blockers. In contrast, administration of the NO synthesis inhibitor N omega-nitro-L-arginine (L-NNA; 300 microM) significantly attenuated AVP-induced dilation to approximately 25%. The addition of K+ channel blockers did not further diminish the vasodilatory response in L-NNA-treated lungs. In conclusion, these results suggest that ATP- and Ca(2+)-sensitive K+ channels are not involved in the pulmonary vasodilatory response to AVP.
Eichinger
M R
MR
Department of Physiology, School of Medicine, University of New Mexico, Albuquerque 87131.
Russ
R D
RD
Walker
B R
BR
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001464:Barium / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008168:Lung / Q000098:blood supply*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019335:Nitroarginine; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001578:Benzopyrans; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011450:Prostaglandin Endoperoxides, Synthetic; D011758:Pyrroles; D013757:Tetraethylammonium Compounds; D014662:Vasoconstrictor Agents; D019806:Cromakalim; D001127:Arginine Vasopressin; D019335:Nitroarginine; D001464:Barium; D013928:Thromboxane A2; D019789:Tetraethylammonium; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; D005905:Glyburide