Antagonism by endothelin of centrally mediated cardiovascular effects of potassium in anaesthetized rats.

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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.