Vasopressin mediates the pressor effects of endothelin in the subfornical organ of the rat.
The potent vasoconstrictor peptide endothelin may affect central cardiovascular function in areas with incomplete blood-brain barrier such as the subfornical organ (SFO). In these studies, we determine whether microinjection of endothelin-1 (ET-1) into the SFO increases blood pressure (BP) in a dose-related manner and investigate the potential involvement of sympathetic and vasopressinergic mechanisms. In urethane-anesthetized 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 evoked a dose-related pressor and bradycardic effect. The maximal changes were 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 antagonist. In animals instrumented for recording of renal sympathetic nerve activity (RSNA), the administration of ET-1 (1 pmol/60 nl) evoked pressor (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 sino-aortic denervated rats, ET-1 pressor effects occur without inhibition of HR or RSNA. We documented the involvement of vasopressin in ET-1 actions by using vasopressin antagonists that inhibited the effects evoked by ET-1 administration. In addition, increases in vasopressin plasma levels were demonstrated at the time of the maximal effect of this peptide. These results indicate that ET-1 acting in the SFO increases BP by a vasopressinergic mechanism.
Mosqueda-Garcia
R
R
Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
Fernandez-Violante
R
R
Hamakubo
T
T
Stainback
R
R
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013356:Subfornical Organ / Q000187:drug effects* / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects; D014667:Vasopressins / Q000097:blood / Q000502:physiology*
D016232:Endothelins; D010456:Peptides, Cyclic; D014667:Vasopressins; C072247:cyclo(Trp-Asp-Pro-Val-Leu)