Characterization of the cardiovascular actions of endothelin in vivo: comparisons with neuropeptide Y and angiotensin II.
The cardiovascular actions of the endothelium-derived peptide endothelin were investigated and characterized in vivo. Intravenous bolus administration of endothelin (4-200 pmol kg-1) in the anaesthetized and chlorisondamine-pre-treated pig caused a dose-dependent increase in mean arterial blood pressure (MABP) with a threshold effect at 20 pmol kg-1 without affecting heart rate. Endothelin induced dose-dependent and long-lasting renal vasoconstriction. A slight effect was observed at 4 pmol kg-1 and the maximal response at 200 pmol kg-1 was a 648 +/- 210% increase in renal vascular resistance. The potency of endothelin in increasing MABP and renal vascular resistance was, on a molar basis, similar to that of angiotensin II and six times higher than that of neuropeptide Y. Administration of the calcium antagonist nifedipine (100 micrograms kg-1 i.v.) markedly inhibited the endothelin-induced increases in MABP and renal vascular resistance. The renal vasoconstrictor responses to angiotensin II and neuropeptide Y were similarily reduced by nifedipine (100 micrograms kg-1). A lower dose of nifedipine (10 micrograms kg-1) slightly attenuated the response to angiotensin II but not that to endothelin or neuropeptide Y. It is concluded that i.v. endothelin induces potent increases in systemic blood pressure and renal vasoconstriction in the pig. Nifedipine reduces the vasoconstrictor response to endothelin but not more than the responses to angiotensin II and neuropeptide Y.
Pernow
J
J
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D009478:Neuropeptide Y; D000804:Angiotensin II; D009569:Nitric Oxide; D009543:Nifedipine