Vasodilatory property of N-alpha benzoyl-L-arginine ethyl ester in the rat isolated pulmonary artery and perfused lung.
L-arginine has been proposed to be the precursor of the endothelium-derived relaxing factor. In this study, we evaluated the pulmonary vascular effects of L-arginine-HCl and its benzoyl derivative N-alpha-benzoyl-L-arginine ethyl ester (BAEE) in the rat, in comparison with other vasodilators such as acetylcholine and sodium nitroprusside. In isolated pulmonary artery rings incubated with indomethacin (10 microM) and precontracted with phenylephrine (2 microM), BAEE (10(-6)-10(-5) M) significantly (P less than .05) relaxed the rings more than L-arginine. This effect was potentiated by the endothelium (P less than .05). The relaxing effect of BAEE (ED50 = 2.1 X 10(-6) M) and acetylcholine (ED50 = 2.4 X 10(-7) M) was significantly less potent than that of sodium nitroprusside (ED50 = 1.1 X 10(-8) M). Moreover, pretreatment with the soluble guanylate cyclase inhibitors methylene blue (10(-5) M) and hemoglobin (10(-5) M) antagonized BAEE-induced relaxation in intact pulmonary rings but had no effect on the relaxation elicited with atrial natriuretic peptide. In the isolated lung preparations perfused with the endoperoxide analog U46619 (5-10 nmol/min), sodium nitroprusside (10(-10)-10(-8) M) elicited potent vasodilation (ED50 = 2.8 X 10(-9) mol) whereas no vasodilation was observed with acetylcholine (10(-8)-10(-5) mol). BAEE (10(-6)-10(-5) M) decreased in a dose-dependent manner pulmonary perfusion pressure, and similar doses of L-arginine showed only a mild vasodilating effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Farhat
M Y
MY
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, D.C.
Thomas
G
G
Cunard
C M
CM
Cole
E
E
Myers
A K
AK
Ramwell
P W
PW
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006454:Hemoglobins / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010477:Perfusion; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D014665:Vasodilator Agents / Q000494:pharmacology*
D006454:Hemoglobins; D014665:Vasodilator Agents; D009569:Nitric Oxide; D001120:Arginine; C009727:benzoylarginine ethyl ester; D000109:Acetylcholine; D008751:Methylene Blue