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1 Clinical Research Department, 2nd Institute of Physiology, Semmelweis University of Medicine, H-1088 Budapest, Hungary; and 2 Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226-0509
Studies were designed to examine
the hypothesis that the renal medulla of Dahl salt-sensitive (Dahl S)
rats has a reduced capacity to generate nitric oxide (NO), which
diminishes the ability to buffer against the chronic hypertensive
effects of small elevations of circulating ANG II. NO synthase (NOS)
activity in the outer medulla of Dahl S rats (arginine-citrulline
conversion assay) was significantly reduced. This decrease in NOS
activity was associated with the downregulation of protein expression
of NOS I, NOS II, and NOS III isoforms in this region as determined by
Western blot analysis. In anesthetized Dahl S rats, we observed that a
low subpressor intravenous infusion of ANG II (5 ng · kg
1 · min1) did not
increase the concentration of NO in the renal medulla as measured by a
microdialysis with oxyhemoglobin trapping technique. In contrast, ANG
II produced a 38% increase in the concentration of NO (87 ± 8 to
117 ± 8 nmol/l) in the outer medulla of Brown-Norway (BN) rats.
The same intravenous dose of ANG II reduced renal medullary blood flow
as determined by laser-Doppler flowmetry in Dahl S, but not in BN rats.
A 7-day intravenous ANG II infusion at a dose of 3 ng · kg1 · min1 did not
change mean arterial pressure (MAP) in the BN rats but increased MAP in
Dahl S rats from 120 ± 2 to 138 ± 2 mmHg (P < 0.05). ANG II failed to increase MAP after NO substrate was provided by infusion of L-arginine (300 µg · kg1 · min1) into the
renal medulla of Dahl S rats. Intravenous infusion of
L-arginine at the same dose had no effect on the ANG
II-induced hypertension. These results indicate that an impaired NO
counterregulatory system in the outer medulla of Dahl S rats makes them
more susceptible to the hypertensive actions of small elevations of ANG II.
Brown-Norway rats; nitric oxide synthase; renal medullary blood flow
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