Item Type: | Article |
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Title: | Pressure natriuresis in AT2 receptor-deficient mice with L-NAME hypertension |
Creators Name: | Obst, M., Gross, V., Janke, J., Wellner, M., Schneider, W. and Luft, F.C. |
Abstract: | AT(2) receptor-disrupted (AT(2) -/-) mice provide a unique opportunity to investigate the cardiovascular and BP-related effects of NO depletion. This study compared the pressure-diuresis-natriuresis relationship in (AT(2) -/-) and wild-type (AT(2) +/+) mice after treating the animals with L-NAME (130 mg/kg body wt per day) for 1 wk. L-NAME increased mean arterial pressure (MAP) more in AT(2) -/- than in AT(2) +/+ mice (118 +/- 2 versus 108 +/- 4 mmHg). This difference occurred even though L-NAME-treated AT(2) +/+ mice had a greater sodium excretion than AT(2) -/- mice (10.9 +/- 0.5 versus 8.0 +/- 1.0 micro mol/h). The pressure-natriuresis relationship in conscious AT(2) -/- mice was shifted rightward compared with controls. RBF was decreased in AT(2) -/- compared with AT(2) +/+ mice. L-NAME decreased RBF in these mice further from 4.08 +/- 0.43 to 2.79 +/- 0.15 ml/min per g of kidney wt. GFR was not significantly different between AT(2) +/+ and AT(2) -/- mice (1.09 +/- 0.08 versus 1.21 +/- 0.09 ml/min per g of kidney wt). L-NAME reduced GFR in AT(2) -/- to 0.87 +/- 0.07 ml/min per g of kidney wt. Fractional sodium (FE(Na)) and water (FE(H2O)) curves were shifted more strongly to the right by L-NAME in AT(2) -/- mice than in AT(2) +/+ mice. AT(1) receptor blocker treatment lowered BP in both L-NAME-treated strains to basal values. It is concluded that the AT(1) receptor plays a key role in the impaired renal sodium and water excretion induced by NO synthesis blockade. Changes in RBF, GFR, and tubular sodium and water reabsorption are involved and may be also responsible for the greater BP increase in L-NAME-treated AT(2) -/- mice. |
Keywords: | Angiotensin Receptors, Blood Pressure, Enzyme Inhibitors, Glomerular Filtration Rate, Hypertension, NG-Nitroarginine Methyl Ester, Natriuresis, Renal Circulation, Type 2 Angiotensin Receptor, Animals, Mice |
Source: | Journal of the American Society of Nephrology |
ISSN: | 1046-6673 |
Publisher: | American Society of Nephrology |
Volume: | 14 |
Number: | 2 |
Page Range: | 303-310 |
Date: | 1 February 2003 |
Official Publication: | http://jasn.asnjournals.org/cgi/content/abstract/14/2/303 |
PubMed: | View item in PubMed |
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