Endothelin-1-induced elevation in blood pressure is independent of increases in sympathetic nerve activity in normotensive rats

This study was performed to determine if endothelin-1 (ET-I)induced pressor responses in urethane-anesthetized, normotensive rats are due to increased sympathetic nerve activity. Renal sympathetic nerve activity (RSNA) was us ed as an index of sympathetic nerve activity. ET-1 (30-1000 pmol/kg) or sar afotoxin (S6c, ETB receptor agonist, 10-3,000 nmol/kg) given by bolus injec tion produced transient decreases in mean arterial pressure (MAP) and incre ases in RSNA and heart rate (HR). ET-1 caused a delayed but sustained incre ase in MAP that was not inhibited by acute sinoaortic denervation or alpha (1)-adrenergic receptor blockade. ET-1 never caused a sustained change in H R or RSNA. A-192621 (ETB receptor antagonist, 12 mg/kg) increased MAP (10-2 0 mm Hg) and decreased HR and RSNA. A-192621 blocked the transient decrease in MAP and increase in RSNA and HR caused by ET-1 and S6c. In A-192621-tre ated rats, ET-1, but not S6c, caused a sustained increase in MAP and decrea se in HR and RSNA. After A-192621 treatment, ET-I infusion caused a sustain ed elevation in MAP; HR and RSNA decreased only after the highest ET-1 dose . These results indicate that the initial increase in RSNA after ET-1 or S6 c is secondary to ETB receptor-mediated vasodilation. Increased RSNA does n ot contribute to ET-1-induced pressor responses; these responses are likely due to vasoconstriction in normotensive, anesthetized rats. Finally, baror eceptor reflexes function after ET-1 or S6c treatment.