Mechanism of action of endothelin-1 in the canine pulmonary circulation. Barman, Scott A., James R. Pauly. Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, Georgia 30912
APStracts 2:0325H, 1995.
Possible mechanisms of action by which Endothelin-1 (ET-1) has an effect on pulmonary vascular resistance and compliance in the canine pulmonary circulation was investigated in the isolated blood perfused dog lung using vascular occlusion techniques. In the present study ET-1 (10-8 M) increased pulmonary vascular resistance and pulmonary capillary pressure by postcapillary vasoconstriction. In addition, ET-1 decreased total vascular compliance and middle compartment compliance. Pretreatment with the ETA receptor antagonist BQ-610 (10 -7 M) or the protein kinase C inhibitors staurosporine (10-6 M) or calphostin C (10-6 M) completely blocked the pressor effect of ET-1. Elimination of extracellular calcium mobilization through voltage dependent calcium channels by verapamil (10-5 M) or modulation of G protein signal transduction by pertussis toxin challenge (15 [mu]g/kg) had no significant effect on the ET-1 induced pulmonary vascular response. The results of the present study indicate that ET -1 causes pulmonary vasoconstriction in the canine pulmonary circulation through ETA receptor mediation and protein kinase C activation possibly leading to intracellular calcium release. In contrast, the ET-1 induced pulmonary vascular response does not appear to involve extracellular calcium entry through voltage dependent calcium channel activation or pertussis toxin sensitive G protein signaling mechanisms. 

Received 19 September 1994; accepted in final form 24 July 1995.
APS Manuscript Number H977-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 August 1995.