Antagonism by endothelin of centrally mediated cardiovascular effects of potassium in anaesthetized rats.
1. We have previously demonstrated that cerebroventricular administration of potassium chloride (KCl) solutions produces dose-dependent reductions in blood pressure and heart rate in anaesthetized rats and that these effects are significantly attenuated by ouabain, a selective inhibitor of the Na(+)-pump. These observations suggest an important relationship between Na+,K(+)-ATPase activity in the central nervous system (CNS) and neural mechanisms involved in the regulation of cardiovascular function. 2. Since endothelin-1 (ET-1) has been shown to affect various ion transport mechanisms, including the Na(+)-pump, the present studies were conducted to evaluate whether this peptide would antagonize central effects of KCl. 3. The present studies demonstrate that cumulative doses of ET-1 (0.8-3.2 pmol, intracerebrolateral ventricular administration, i.c.v.) produced significant attenuation of hypotension and bradycardia produced by i.c.v. injections of KCl (0.75 mumol/5 microL, i.c.v.); in a separate series, a single high dose of ET-1 (4.0 pmol, i.c.v.) significantly reduced cardiovascular responses to various doses of KCl (0.375, 0.75, 1.25 mumol/5 microL, i.c.v.). 4. These studies suggest that endothelin may be involved in the regulation of arterial pressure since it is present in CNS and possesses a ouabain-like effect. However, it is not conclusive that ET-1 inhibits neuronal Na(+)-pump, since alternative mechanisms can also account for the efficacy of the peptide to antagonize central effects of potassium chloride.
Shah
J
J
Department of Pharmacology, University of Houston, Texas 77204-5515.
Jandhyala
B S
BS
D000818:Animals; D001693:Biological Transport, Active; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D011189:Potassium Chloride / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains
D016232:Endothelins; D011189:Potassium Chloride