Role of endothelium-derived nitric oxide in the regulation of blood pressure.

Key Points

• To investigate whether basal synthesis of endothelium-derived nitric oxide from L-arginine regulates systemic arterial blood pressure and mediates acetylcholine-induced vasodilation.
• Administered N omega-monomethyl-L-arginine (L-NMMA; 3–100 mg/kg) or its D-enantiomer intravenously to anesthetized rabbits to evaluate blood pressure responses.
• Assessed blood pressure responses to acetylcholine and glyceryl trinitrate before and after L-NMMA administration, with pharmacological reversals tested using L-arginine (300 mg/kg), D-arginine, indomethacin, prazosin, and vagotomy.
• Measured nitric oxide release ex vivo from perfused aortic segments following in vivo L-NMMA treatment.
• L-NMMA induced a dose-dependent, sustained increase in mean systemic arterial blood pressure lasting 15 to 90 minutes, an effect not observed with its D-enantiomer.
• L-NMMA (100 mg/kg) significantly inhibited the hypotensive response to acetylcholine without altering the response to glyceryl trinitrate; both blood pressure elevation and acetylcholine inhibition were reversed by L-arginine, but not by D-arginine, indomethacin, prazosin, or vagotomy.
• In vivo L-NMMA treatment was associated with significant inhibition of nitric oxide release from perfused aortic segments ex vivo, which was fully reversed by infusing L-arginine.