Effects of the endothelin (ET) receptor antagonist BQ 123 on initial and delayed vascular responses induced by ET-1 in conscious, normotensive rats.
The ETA receptor antagonist, BQ 123 was used to characterize depressor and initial and delayed pressor responses to ET-1 in conscious rats. BQ 123 (0.001-0.01 mumol/kg/min) dose-dependently inhibited the initial ET-1 (0.1 nmol/kg) pressor response, reaching a maximum after 0.01 BQ 123 (61 +/- 4% inhibition). Less inhibition of the pressor effects occurred after higher doses of BQ 123 (1: 10 +/- 6% inhibition). The depressor response to 1 nmol/kg ET-1 was unchanged by BQ 123 (0.01), but inhibited by BQ 123 (1). The initial pressor response to 1.0 nmol/kg ET-1 was inhibited by BQ 123 (0.01: 26 +/- 6%; 1.0: 41 +/- 3% inhibition). The delayed pressor response, 180 min post-ET-1 (+41 +/- 2% increase) was reduced by BQ 123 infused before the delayed peak (+14 +/- 5% increase). Plasma immunoreactive ET values were: control: 5.4 +/- 0.4; initial peak: 491.4 +/- 50.6; delayed peak: 8.2 +/- 0.6 fmol/ml. The delayed ET-1 response does not coincide with sustained high circulating levels of immunoreactive ET, but inhibition of the response by BQ 123 suggests that it may involve endothelin receptors.
Bird
J E
JE
Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543.
Waldron
T L
TL
Dorso
C R
CR
Asaad
M M
MM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000097:blood / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D012016:Reference Values; D013997:Time Factors
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; C072247:cyclo(Trp-Asp-Pro-Val-Leu)