(Hypertension. 1997;29:969-975.)
© 1997 American Heart Association, Inc.
Articles |
Role of Nitric Oxide in the Development of Vascular 
1-Adrenoreceptor Desensitization and Pressure Diuresis in Conscious Rats
From The Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Correspondence to Naoyoshi Minami, MD, The Second Department of Internal Medicine, Tohoku University School of Medicine, 1-1 Seiryou-cho, Aoba-ku, Sendai 980, Japan.
Abstract We evaluated whether a minor impairment of the
L-arginine–nitric oxide pathway would affect the
desensitization of vascular -adrenoreceptor and
pressure diuresis induced by prolonged intravenous
infusion of phenylephrine (an
-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
-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
-adrenoreceptor but does inhibit the
pressure-diuresis response in conscious normotensive rats.
Key Words: nitric oxide • receptors, adrenergic alpha • desensitization, adrenergic • diuresis • rats