Endogenous nitric oxide reduces the efficacy of the endothelin system to maintain blood pressure during high epidural anaesthesia in conscious dogs

Background and objective: During high epidural anaesthesia, endothelin only contributes minimally to blood pressure stabilization. This phenomenon could result from the inhibitory action of nitric oxide on the endothelin system. To clarify this, we studied the interaction between nitric oxide and endothelin during high epidural anaesthesia in conscious dogs, in comparison to the interaction of nitric oxide and vasopressin. Methods: Six animals were used in 45 individual experiments randomly arranged as follows: N-ω-nitro- arginine-methylester 0.3-10 mg kg-1 under physiological conditions or during high epidural anaesthesia (lidocaine 1%) and N-ω-nitro-arginine- methylester (L-NAME) 0.3-10 mg kg-1 after preceding endothelin (Tezosentan®) or vasopressin (β-mercapto-β,β-cyclo-penta- methylene-propionyl-O-Me-Tyr-Arg-vasopressin) receptor blockade under physiological conditions or during high epidural anaesthesia. During control experiments normal saline was injected either intravenously (n = 5) or into the epidural space (n = 4). Results: N-ω-nitro-arginine-methylester increased mean arterial pressure dose-dependently in all groups. However, this effect was substantially reduced in the presence of the endothelin receptor antagonist compared to N-ω-nitro-arginine-methylester alone, both under control conditions (7 ± 3 vs. 21 ± 3 mmHg; P < 0.05) and during high epidural anaesthesia (17 ± 3 vs. 30 ± 1 mmHg; P < 0.05). Blockade of vasopressin showed no similar relationship with N-ω-nitro- arginine-methylester. Conclusions: The diminished increase in mean arterial pressure after injection of N-ω-nitro-arginine-methylester only during endothelin receptor blockade indicates that endogenous nitric oxide inhibits the action of endothelin during high epidural anaesthesia and might thus explain the reduced efficacy of endothelin in maintaining blood pressure during high epidural anaesthesia.