Impaired nitric oxide-dependent responses and their recovery in hypertensive pulmonary arteries of rats.
To study the changes of endothelium-dependent and -independent relaxation in structurally remodeled pulmonary arteries with hypoxic pulmonary hypertension and their reversibility during recovery in room air, rats were exposed to hypobaric hypoxia (air at 380 mmHg) for 10 days and then allowed to recover in room air for 3, 14, 28, or 56 days. Relaxation by acetylcholine, sodium nitroprusside (SNP), and isoproterenol was depressed in large- and small-conduit pulmonary arterial rings from rats exposed to 10 days of hypoxia. The relaxant response to isoproterenol and SNP was normalized completely after 3 and 28 days of recovery, respectively. The relaxation by acetylcholine was still impaired at high concentrations after 56 days. A cyclooxygenase inhibitor, indomethacin, enhanced relaxation by acetylcholine of rings from experimental rats but not from control rats. Endothelium-denuded rings showed no difference in the response to acetylcholine between control and experimental rats. In conclusion, the impaired response to acetylcholine may be related to acetylcholine-induced, cyclooxygenase-dependent production of a vasoconstrictor by endothelial cells and to depressed smooth muscle response to nitric oxide (NO). During recovery, the NO-induced guanosine 3',5'-cyclic monophosphate-dependent dilation returned to normal. However, the release of cyclooxygenase-dependent production of a vasoconstrictor may persist even after 56 days of recovery.
Maruyama
J
J
Department of Anesthesiology, Mie University School of Medicine, Japan.
Maruyama
K
K
D000818:Animals; D001835:Body Weight; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000473:pathology; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009569:Nitric Oxide; D011189:Potassium Chloride; D015237:Dinoprost