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Inhibition by phosphoramidon of the regional haemodynamic effects of proendothelin−2 and −3 in conscious rats
Author(s) -
Gardiner S.M.,
Kemp P.A.,
Bennett T.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb12787.x
Subject(s) - phosphoramidon , vasoconstriction , vasodilation , medicine , hemodynamics , endocrinology , vasoconstrictor agents , endothelin receptor , endothelins , chemistry , receptor
1 Regional haemodynamic studies were carried out in conscious, Long Evans rats, chronically‐instrumented with pulsed Doppler flow probes and intravascular catheters. 2 In the first experiment, proendothelin‐2 and −3 (0.1 and 1.0 nmol kg −1 , i.v. boluses) were found to cause dose‐dependent pressor, bradycardic, and renal and, particularly, mesenteric vasoconstrictor effects. The hindquarters showed an initial vasodilatation (which was not dose‐dependent) followed by a vasoconstriction (which was dose‐related). The pressor and renal and mesenteric vasoconstrictor effects of proendothelin‐3 were greater than those of proendothelin‐2. 3 In the second experiment, it was demonstrated that phosphoramidon (10 μmol kg −1 , i.v. bolus) abolished the pressor, bradycardic, and hindquarters vasoconstrictor effects of proendothelin‐2 (1.0 nmol kg −1 ), and inhibited significantly the renal and mesenteric vasoconstrictor actions of this peptide. Phosphoramidon had similar effects on the responses to proendothelin‐3 (1.0 nmol kg −1 ), although a slight pressor effect of this peptide remained in the presence of phosphoramidon. 4 In the third experiment, it was found that phosphoramidon had no significant effect on the pressor or vasoconstrictor responses to endothelin‐2 or −3 (0.1 nmol kg −1 ). 5 Collectively, the results indicate that the haemodynamic effects of proendothelin‐2 and −3 in vivo in conscious rats are probably due to their conversion to endothelin‐2 and −3, respectively, by an enzyme(s) that is inhibited by phosphoramidon. There appears to be no obvious difference between proendothelin‐2, proendothelin‐3 and proendothelin‐1 in this respect.