Differential role of vasoactive prostanoids in porcine and human isolated pulmonary arteries in response to endothelium‐dependent relaxants

Abstract

1 The pig is increasingly being used in medical research, both as a model of the human cardiovascular system, and as a possible source of organs for xenotransplantation. However, little is known about the comparative functions of the vascular endothelium between porcine and human arteries. We have therefore compared the e ects of two endothelium-dependent vasorelaxants, acetylcholine (ACh) and the Ca 2+ -ATPase inhibitor, cyclopiazonic acid (CPA) on the porcine and human isolated pulmonary artery using isometric tension recording. 2 ACh and CPA produced endothelium-dependent relaxations of both the human and porcine pulmonary arteries. 3 In the porcine pulmonary artery, the cyclo-oxygenase inhibitor,¯urbiprofen had no e ect on relaxations to ACh (E max : control 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 inhibitor, L-NAME converted relaxations to both ACh and CPA into contractile responses (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 presence of L-NAME were abolished by¯urbiprofen. 4 In the human pulmonary artery, L-NAME and¯urbiprofen partly attenuated relaxations to ACh (E max : control: 45.1+12.1%;¯urbiprofen: 33.4+13.5%; L-NAME: 10.1+7.2%) and CPA (E max : control: 78.1+5.5%;¯urbiprofen: 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 have demonstrated that while the release of nitric oxide is important in responses to endotheliumdependent vasorelaxants in both human and porcine pulmonary arteries, in the human arteries, there is an important role for vasorelaxant prostanoids whilst in the porcine arteries, vasoconstrictor prostanoids are released.

Characterization of agonist-induced vasoconstriction in mouse pulmonary artery

“…The contractile response we observed in mouse PA rings to vasoactive substances like ET-1, 5-HT, and the thromboxane A 2 analog U-44619 were characteristically similar to that observed in PA from other species (8,10,11,24,25,33,37,42,43,52,55,60,69). The contractile response to thrombin observed in mouse PA rings was also similar to that observed by others in porcine PA rings (21).…”

Molecular Mechanisms Regulating the Vascular Prostacyclin Pathways and Their Adaptation during Pregnancy and in the Newborn

“…The observation that the COX inhibitor indomethacin reduces ACh relaxation in isolated human pulmonary artery but not in the pulmonary vein supports little role of PGI 2 in relaxation of pulmonary vein. In contrast, NO seems to be the sole endothelium-derived vasorelaxant released by ACh in porcine pulmonary artery (Lawrence et al, 1998;Norel et al, 2004). In canine pulmonary vessels, PGI 2 does not contribute to endothelium-dependent relaxation in the large arterial rings but has an important vasodilator effect in the small microvessels.…”

Type 2 Diabetic Individuals Have Impaired Leg Blood Flow Responses to Exercise

“…Acetylcholine mediates vasodilation through interaction with the endothelial M 3 muscarinic receptor (19) to release NO and vasodilator prostanoids, which diffuse to the underlying smooth muscle and initiate vasorelaxation (20,21). Thus, either the endothelial mechanisms for acetylcholine-stimulated release of NO or prostanoids or arterial smooth muscle reactivity to these substances is reduced in type 2 diabetic subjects.…”