Role of nitric oxide in the development of vascular alpha 1-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 alpha-adrenoreceptor and pressure diuresis induced by prolonged intravenous infusion of phenylephrine (an alpha-adrenoreceptor agonist) in conscious Wistar-Kyoto rats. We examined dose-pressor-response curves to phenylephrine after an intravenous infusion of phenylephrine (2.5 micrograms.kg-1.min-1) or saline for 9 hours with and without concomitant infusion of N omega-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 micrograms.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 micrograms.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 microgram/kg) and -untreated (0.79 +/- 0.06 versus 1.08 +/- 0.03 micrograms/kg) rats. The log ED50 value after phenylephrine infusion (5 micrograms.kg-1.min-1) was significantly higher than that after furosemide injection (1.28 +/- 0.06 versus 1.02 +/- 0.01 micrograms/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 alpha-adrenoreceptor but does inhibit the pressure-diuresis response in conscious normotensive rats.
Minami
N
N
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Imai
Y
Y
Nishiyama
H
H
Abe
K
K
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003627:Data Interpretation, Statistical; D003888:Desensitization, Immunologic; D004231:Diuresis; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D010953:Plasma Volume; D051381:Rats; D011921:Rats, Inbred WKY; D018340:Receptors, Adrenergic, alpha-1 / Q000276:immunology*
D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester