VASOPRESSIN MEDIATES THE PRESSOR EFFECTS OF ENDOTHELIN IN THE SUBFORNICAL ORGAN OF THE RAT

The potent vasoconstrictor peptide endothelin may affect central cardi ovascular function in areas with incomplete blood-brain barrier such a s the subfornical organ (SFO). In these studies, we determine whether microinjection of endothelin-1 (ET-1) into the SFO increases blood pre ssure (BP) in a dose-related manner and investigate the potential invo lvement of sympathetic and vasopressinergic mechanisms. In urethane-an esthetized Sprague-Dawley rats, BP was recorded intra-arterially, and ET-1 (0.125-6.0 pmol/60 nl) was microinjected stereotaxically into the SFO. Whereas vehicle (60 nl) did not change mean BP or HR, ET-1 evoke d a dose-related presser and bradycardic effect. The maximal changes w ere noted at the 1-pmol dose. No significant hemodynamic effects were observed with ET-1 microinjection in areas immediately surrounding the SFO or into the SFO of rats pretreated with a specific endothelin ant agonist. In animals instrumented for recording of renal sympathetic ne rve activity (RSNA), the administration of ET-1 (1 pmol/60 nl) evoked presser (14 +/- 5 mm Hg) and bradycardic (-41 +/- 12 bpm) effects with a decrease in RSNA (-16% +/- 3%). The effects on HR and RSNA seem to be mediated by baroreflex changes because in sine-aortic denervated ra ts, ET-1 presser effects occur without inhibition of HR or RSNA. We do cumented the involvement of vasopressin in ET-1 actions by using vasop ressin antagonists that inhibited the effects evoked by ET-1 administr ation. In addition, increases in vasopressin plasma levels were demons trated at the time of the maximal effect of this peptide. These result s indicate that ET-1 acting in the SFO increases BP by a vasopressiner gic mechanism.