Proteinase-activated receptor (PAR)-mediated vasorelaxation in pulmonary arteries from normotensive and hypoxic pulmonary hypertensive rats.
Proteinase-activated receptor (PAR)-mediated vasorelaxant responses were examined in main pulmonary artery preparations from control rats and rats exposed to hypoxia (10% oxygen) for 1 or 4 weeks to induce pulmonary hypertension. Trypsin and the PAR-2 peptide, SLIGRL, relaxed phenylephrine precontracted preparations, with maximum responses the same as the maximum response to acetylcholine. Responses to trypsin and SLIGRL were abolished by endothelium removal or a nitric oxide (NO) synthase inhibitor, and were, therefore, due to release of endothelium-derived NO. In pulmonary arteries from rats exposed to hypoxia for 1 week, the potencies and maximal responses for acetylcholine and trypsin were markedly reduced compared with data in control rats, but these values were restored to normal in arteries from 4-week hypoxic rats. In contrast, the potency of SLIGRL was unchanged in arteries from either group of hypoxic rats. The data for trypsin and acetylcholine are consistent with previous findings for a variety of endothelium-dependent vasodilators and reflect an impairment of endothelial function in early hypoxic pulmonary hypertension. The data for SLIGRL emphasise that one cannot necessarily predict changes in PAR-2-mediated endothelium-dependent vasorelaxation in disease states from data with the classical endothelium-dependent vasodilator, acetylcholine.
Wanstall
Janet C
JC
Department of Physiology and Pharmacology, School of Biomedical Sciences, University of Queensland, St Lucia, Brisbane, Qld 4072, Australia. wanstall@mailbox.uq.edu.au
Gambino
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D011651:Pulmonary Artery / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D044464:Receptor, PAR-2 / Q000502:physiology*; D014357:Trypsin / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D009842:Oligopeptides; D044464:Receptor, PAR-2; D014665:Vasodilator Agents; C099570:seryl-leucyl-isoleucyl-glycyl-arginyl-leucine; D014357:Trypsin; D000109:Acetylcholine