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Articles in PresS, published online ahead of print April 4, 2002
Am J Physiol Regu Physiol, 10.1152/ajpregu.00461.2001
Submitted on August 2, 2001
Accepted on March 29, 2002
1 Clinical Research Department-2nd Institute of Physiology, Semmelweis University of Medicine, Budapest, Hungary
2 Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
* To whom correspondence should be addressed. E-mail: cowley{at}mcw.edu.
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 angiotensin II (AngII). Nitric oxide 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 down regulation 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 i.v. infusion of AngII (5 ng/kg/min) did not increase the concentration of NO in the renal medulla as measured by a microdialysis with oxyhemoglobin trapping technique. In contrast, AngII produced a 38 % increase in the concentration of NO (87±8 to 117±8 nmol/L) in the outer medulla of Brown Norway rats. The same i.v. dose of AngII reduced renal medullary blood flow as determined by laser-Doppler flowmetry in Dahl S, but not in BN rats. A 7-day i.v. AngII infusion at a dose of 3 ng/kg/min 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). AngII failed to increase MAP after NO substrate was provided by infusion of L-arginine (300 :g/kg/min) into the renal medulla of Dahl S rats. Intravenous infusion of L-arginine at the same dose had no effect on the AngII-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 AngII.
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