TY - JOUR
T1 - Mechanism of action of endothelin-1 in the canine pulmonary circulation
AU - Barman, S. A.
AU - Pauly, J. R.
PY - 1995
Y1 - 1995
N2 - Possible mechanisms of action by which endothelin (ET)-1 has an effect on pulmonary vascular resistance and compliance in the canine pulmonary circulation were investigated in the isolated blood-perfused dog lung by use of 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 ET(A) receptor antagonist BQ-610 (10-7 M) or the protein kinase C inhibitors staurosporine (10-6 M) and 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 μg/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 ET(A) 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.
AB - Possible mechanisms of action by which endothelin (ET)-1 has an effect on pulmonary vascular resistance and compliance in the canine pulmonary circulation were investigated in the isolated blood-perfused dog lung by use of 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 ET(A) receptor antagonist BQ-610 (10-7 M) or the protein kinase C inhibitors staurosporine (10-6 M) and 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 μg/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 ET(A) 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.
KW - G proteins
KW - calcium
KW - endothelin A receptors
KW - pertussis toxin
KW - protein kinase C
KW - pulmonary vascular compliance
KW - pulmonary vascular resistance
KW - vasoconstriction
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U2 - 10.1152/jappl.1995.79.6.2014
DO - 10.1152/jappl.1995.79.6.2014
M3 - Article
C2 - 8847268
AN - SCOPUS:0029591695
SN - 8750-7587
VL - 79
SP - 2014
EP - 2020
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
IS - 6
ER -