CARDIOVASCULAR EFFECTS OF ENDOTHELIN INJECTED INTO BRAIN NUCLEI REGULATING VASOPRESSIN RELEASE

We studied the cardiovascular effects produced by administration of en dothelin-1 (ET-1) into brain nucleic known to affect vasopressin relea se. In urethane anesthetized Sprague-Dawley rats, microinjection of ET -1 into the subfornical organ (SFO) resulted in a dose-dependent incre ase in arterial blood pressure and a decrease in heart rate. These eff ects were inhibited by previous administration of the ET(A) receptor a ntagonist BQ-123 or by intravenous administration of a vasopressin ant agonist. In addition, microinjection of ET-1 into the SFO increased pl asma levels of vasopressin. In contrast, in the paraventricular nucleu s (PVN) of the hypothalamus microinjection of ET-1 evoked a dose-relat ed bradycardia with inconsistent changes in blood pressure. Although t he bradycardia was antagonized by intra-PVN administration of BQ-123, the vasopressin antagonist did not affect the changes in heart rate ev oked by microinjection of this peptide into the PVN. Overall, these re sults indicate that the central cardiovascular effects of ET-1 result from activation of several mechanisms, including stimulation of brain centers regulating vasopressin release.