Loss of endothelium-dependent relaxation in proximal pulmonary arteries from rats exposed to chronic hypoxia: effects of in vivo and in vitro supplementation with L-arginine.
To explore endothelium-dependent relaxation and the L-arginine (L-ARG)-nitric oxide (NO) pathway during chronic hypoxia, we examined isolated rings from large conduit pulmonary arteries and aorta from rats exposed to either room air (N), 3-week hypoxia (H), or 3-week H followed by 72-h recovery to normoxia (room air). We examined the vasodilatory actions of acetylcholine (ACh), ionophore A23187, and endothelin-3 (ET-3) on extrapulmonary left and right branches of pulmonary arteries and thoracic aorta precontracted by phenylephrine (PE 10(-6) M). Endothelium-dependent relaxation of N rat pulmonary arteries and aorta to ACh and A23187 was abolished in the presence of L-NG nitroarginine methyl ester (L-NAME 10(-4) M) or methylene blue (MB 10(-5) M) but was suppressed only partially by NG-monomethyl-L-arginine (L-NMMA 5 x 10(-4) M). In pulmonary arteries but not in aorta, ET-3 induced endothelium-dependent relaxation that was suppressed by L-NAME, MB, and L-NMMA. Pulmonary arteries from H rats did not relax with ET-3. As compared with those of N rats, they exhibited less relaxation to ACh and A23187, (47 +/- 3 vs. 89 +/- 2 and 53 +/- 2 vs. 85 +/- 4%, p < 0.001, respectively) but exhibited similar relaxation to the nonendothelium-dependent vasodilator linsidomine. In contrast, endothelial-relaxation did not differ between N and H rat aorta.2+ pretreatment with L-ARG.
Carville
C
C
Département de Physiologie, Institut National de la Santé et de la Recherche Médicale, Hôpital Henri-Mondor, Créteil, France.
Raffestin
B
B
Eddahibi
S
S
Blouquit
Y
Y
Adnot
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000097:blood / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D016232:Endothelins; D014665:Vasodilator Agents; D010656:Phenylephrine; D000001:Calcimycin; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine; D000109:Acetylcholine