DIFFERENTIAL ROLE OF VASOACTIVE PROSTANOIDS IN PORCINE AND HUMAN ISOLATED PULMONARY-ARTERIES IN RESPONSE TO ENDOTHELIUM-DEPENDENT RELAXANTS

1 The pig is increasingly being used in medical research, both as a mo del of the human cardiovascular system, and as a possible source of or gans for xenotransplantation. However, little is known about the compa rative functions of the vascular endothelium between porcine and human arteries. We have therefore compared the effects of two endothelium-d ependent vasorelaxants, acetylcholine (ACh) and the Ca2+-ATPase inhibi tor, cyclopiazonic acid (CPA) on the porcine and human isolated pulmon ary artery using isometric tension recording. 2 ACh and CPA produced e ndothelium-dependent relaxations of both the human and porcine pulmona ry arteries. 3 In the porcine pulmonary artery, the cyclo-oxygenase in hibitor, flurbiprofen had no effect on relaxations to ACh (E-max: cont rol 67.8+/-8.8% versus 72.4+/-9.5% (n=11)) or CPA (E-max: control 79.6 +/-5.0% versus 94.0+/-10.6% (n=7)). The nitric oxide synthase inhibito r, L-NAME converted relaxations to both ACh and CPA into contractile r esponses (maximum response: ACh 30.0+/-11.1% (n= 10); CPA 80.4+/-26.2% (n=8) of U46619-induced tone). These contractile responses in the pre sence of L-NAME were abolished by flurbiprofen. 4 In the human pulmona ry artery, L-NAME and flurbiprofen partly attenuated relaxations to AC h (E-max: control: 45.1 +/- 12.1%; flurbiprofen: 33.4 +/- 13.5%; L-NAM E: 10.1 +/- 7.2%) and CPA (E-max: control: 78.1 +/- 5.5%; flurbiprofen : 69.6 +/- 7.2%; L-NAME 37.9 +/- 10.7% of U46619-induced tone). These responses were abolished by the combination of both inhibitors. 5 We h ave demonstrated that while the release of nitric oxide is important i n responses to endothelium-dependent vasorelaxants in both human and p orcine pulmonary arteries, in the human arteries, there is an importan t role for vasorelaxant prostanoids whilst in the porcine arteries, va soconstrictor prostanoids are released.