Role of nitric oxide in the development of vascular α₁-adrenoreceptor desensitization and pressure diuresis in conscious rats

We evaluated whether a minor impairment of the L-arginine-nitric oxide pathway would affect the desensitization of vascular α-adrenoreceptor and pressure diuresis induced by prolonged intravenous infusion of phenylephrine (an α-adrenoreceptor agonist) in conscious Wistar-Kyoto rats. We examined dose-pressor-response curves to phenylephrine after an intravenous infusion of phenylephrine (2.5 μg · kg^-1 · min^-1) or saline for 9 hours with and without concomitant infusion of N(ω)-L-arginine methyl ester (L-NAME) given to partially inhibit the L-arginine-nitric oxide pathway. In addition, to evaluate the effect of plasma volume loss on the pressor response to phenylephrine, we evaluated the dose-pressor-response curves to phenylephrine after intravenous injection of furosemide (5 mg/kg) or infusion of phenylephrine (5 μg · kg^-1 · min^-1) for 9 hours. The renin- angiotensin, vasopressin and autonomic nervous systems were blocked before the examination of dose-pressor responses. Prolonged infusion of phenylephrine (2.5 μg · kg^-1 · min^-1) shifted the dose pressor- response curve to this agent rightward, with significantly increased log ED₅₀ (the dose needed to reach 50% of the maximal response) to a similar extent in both L-NAME-treated (0.51±0.05 versus 0.93±0.07 μg/kg) and untreated (0.79±0.06 versus 1.08±0.03 μg/kg) rats. The log ED₅₀ value after phenylephrine infusion (5 μg · kg^-1 · min^-1) was significantly higher than that after furosemide injection (1.28±0.06 versus 1.02±0.01 μg/kg, respectively, P<.01), although the two treatments induced a similar loss of plasma volume. The slope in the linear relationship between the average change in mean arterial pressure during the 9-hour infusion period and the rate of urine excretion was significantly depressed in L-NAME treated versus control rats (L-NAME: 0.057 mL · kg^-1 · h^-1 · mm Hg^-1, control: 0.146 mL · kg^-1 · h^-1 · mm Hg^-1, P<.05). In conclusion, a minor impairment of the L-arginine-nitric oxide pathway does not appear to interfere with the desensitization of vascular α-adrenoreceptor but does inhibit the pressure-diuresis response in conscious normotensive rats.