Published online before print August 16, 2004, doi: 10.1161/01.HYP.0000140924.91479.03
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(Hypertension. 2004;44:424.)
© 2004 American Heart Association, Inc.
Scientific Contributions |
Inhibition of Cyclooxygenase-2 in the Rat Renal Medulla Leads to Sodium-Sensitive Hypertension
From the Department of Physiology, Medical College of Wisconsin, Milwaukee.
Correspondence to David L. Mattson, PhD, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail dmattson{at}mcw.edu
Cyclooxygenase-2 expression in the renal medulla is regulated by dietary salt intake. The present study was performed to determine the influence of chronic inhibition of medullary cyclooxygenase-2 on arterial blood pressure in conscious Sprague-Dawley rats maintained on a high-salt (4% NaCl) or a low-salt (0.4% NaCl) diet. Rats were uninephrectomized and instrumented with femoral arterial and femoral vein or renal medullary interstitial catheters. Each rat received a continuous medullary or intravenous infusion of saline (0.5 mL per hour) for 3 control days, followed by infusion of the cyclooxygenase-2 inhibitor NS-398 (10 mg/kg per day) for 5 days. Medullary interstitial infusion of NS-398 significantly increased mean arterial pressure in the 4% NaCl group from 126±2 to 146±2 mm Hg (n=6) but did not alter blood pressure in the 0.4% NaCl group (n=6). Intravenous infusion of NS-398 to rats on the 4.0% NaCl diet also failed to alter mean arterial pressure (n=5). To test the blood pressure effect of a mechanistically different inhibitor of cyclooxygenase-2, an antisense oligonucleotide against cyclooxygenase-2 (18-mer; 8 nmol per hour) was infused into the renal medulla of rats maintained on a high-salt diet. Administration of the antisense oligonucleotide reduced cyclooxygenase-2 immunoreactive protein by 36% and significantly increased mean arterial pressure from 127±2 to 147±2 mm Hg (n=6). Renal medullary interstitial infusion of a scrambled oligonucleotide did not alter arterial pressure (n=5). These results demonstrate the importance of cyclooxygenase-2 in the renal medulla in maintaining blood pressure during high-salt intake.
Key Words: kidney • prostaglandins • cyclooxygenase • rats • blood pressure
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