Antagonism of renal and systemic responses to endothelin-1 infusion with PD 145065.
The antagonism by PD 145065 (Ac-D-Bhg-L-Leu-L-Asp-L-Ile-L-Ile-L-Trp; D-Bhg = 5H-dibenzyl[a,d]cycloheptene-10,11-dihydroglycine), a non-selective endothelin ETA and ETB receptor antagonist, of the pressor and renal haemodynamic responses to an infusion of endothelin-1 was investigated in the anaesthetised rat. Infusion of endothelin-1 at 2 or 4 pmol/min/rat for 2 h produced a significant increase in mean arterial blood pressure and renal vascular resistance. Glomerular filtration rate was reduced by both infusion rates of endothelin-1 (-34% for the lower rate and -72% for the higher rate), but only the high rate significantly reduced renal blood flow (-64%). These effects of endothelin-1 were completely blocked by infusion of PD 145065 (0.05 mg/min/rat), demonstrating the efficacy of this antagonist in preventing the actions of endothelin-1 in vivo. These results lend support to an involvement of endothelin ETB receptors in the renal effects of endothelin-1.
Wellings
R P
RP
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, UK.
Corder
R
R
Doherty
A M
AM
Vane
J R
JR
D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006400:Hematocrit; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D009842:Oligopeptides; C082887:PD 145065