Cardiovascular effects of endothelin injected into brain nuclei regulating vasopressin release

We studied the cardiovascular effects produced by administration of endothelin-1 (ET-1) into brain nucleic known to affect vasopressin release. In urethane-anesthetized Sprague-Dawley rats, microinjection of ET-1 into the subfornical organ (SFO) resulted in a dose-dependent increase in arterial blood pressure and a decrease in heart rate. These effects were inhibited by previous administration of the ETA receptor antagonist BQ-123 or by intravenous administration of a vasopressin antagonist. In addition, microinjection of ET-1 into the SFO increased plasma levels of vasopressin. In contrast, in the paraventricular nucleus (PVN) of the hypothalamus microinjection of ET-1 evoked a dose-related bradycardia with inconsistent changes in blood pressure. Although the bradycardia was antagonized by intra-PVN administration of BQ-123, the vasopressin antagonist did not affect the changes in heart rate evoked by microinjection of this peptide into the PVN. Overall, these results indicate that the central cardiovascular effects of ET-1 result from activation of several mechanisms, including stimulation of brain centers regulating vasopressin release.