SENSITIZATION OF BARORECEPTOR REFLEX BY CENTRAL ENDOTHELIN IN CONSCIOUS RATS

Effect of centrally administered endothelins (ETs) on cardiovascular regulation was investigated in conscious normotensive rats. ET-1, ET-2, or ET-3 was injected through a cannula into the cisterna magna, and mean arterial pressure (MAP) and heart rate (HR) were measured through a cannula in the femoral artery. Baroreceptor HR reflex was measured by monitoring the changes in HR in response to changes in MAP induced by slow intravenous injection of phenylephrine or nitroprusside. MAP and HR responses were then analyzed in individual animals by sigmoidal curve fitting. Intracisternal (ic) administration of ET-1 did not change resting MAP or HR at doses of 2.5 or 25 pmol/kg. The higher dose of ET-1 induced a significant increase of baroreflex sensitivity without a change of HR range. Sympathetic and vagal components of the baroreflex were examined by testing reflex responses after pretreatment with methylatropine (0.5 mg/kg iv) and atenolol (1.0 mg/kg iv), respectively. An increased baroreflex sensitivity was observed after ET-1 treatment in the atenolol-treated rats but not in the methylatropine-treated rats, suggesting that the peptide selectively affected the vagal component of the reflex. Intravenous 25 pmol/kg ET-1 did not cause an increase in baroreflex sensitivity. Neither ET-2 nor ET-3 (25 pmol/kg ic) induced changes in resting MAP or HR, but both significantly increased baroreflex sensitivity without changes in HR range. Order of potency of the ETs on baroreflex gain was ET-3 greater-than-or-equal-to ET-1 > ET-2. In conclusion, ETs, at doses that do not change resting values for MAP or HR, may induce significant centrally mediated sensitization of the baroreceptor HR reflex. Central ET may play an important role in modulation of cardiovascular homeostasis.