In vitro effect of endothelin-1 and nifedipine on pulmonary vascular contraction of pulmonary hypertensive and non-pulmonary hypertensive chickens

Abstract

ABSTRACTEndothelin-1 (ET-1) is relevant to the pathogenesis of pulmonary arterial hypertension (PAH) in several species, including broiler chickens. In ET-1-induced vasoconstriction, L-type voltage-operated calcium channels (VOCCs) play a crucial role. In this study, the effect that ET-1 and the calcium channel blocker (CCB) nifedipine have on ET-1-induced vascular contraction in pulmonary artery rings of both, non-pulmonary hypertensive chickens (NPHC) and pulmonary hypertensive chickens (PHC), was evaluated. A significant increase response in ET-1 was observed for PHC vascular rings with respect to those of NPHC (p < .05). Incubation with 1 μM nifedipine did not completely reverse the contraction induced by 1 × 10−7 M ET-1 in both NPHC and PHC rings, suggesting the participation of additional calcium sources procured via influx through L-type VOCC. Nifedipine reduced, to a higher degree, the contraction induced by ET-1 in NPHC (50%) when compared with that observed in PHC rings (30.7%). Thus, the ET-1-induced vasoconstriction processes are more efficient in PHC, and the influx of calcium into the cell through the L-type VOCC is presumably only a fraction of the necessary calcium for ET-1-induced vasoconstriction. It is suggested that blocking calcium uptake through alternative pathways (receptor-operated calcium channels and storage-operated calcium channels) may produce a vasodilation effect of considerable therapeutic significance in PHC.