Article
COX-2-dependent sodium and fluid retention in chronically and acutely stimulated renin system in men
COX-2-abhängige Natrium- und Wasserretention während chronischer und akuter Stimulation des Reninsystems
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Published: | November 11, 2004 |
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In several conditions with a stimulated renin system kidney function strongly dependent on intact formation of prostaglandins. In these conditions inhibition of cyclooxygenase may cause detrimental damage to renal function. Our study aimed to assess the influenc of selective cyclooxygenase-2 (COX-2)-inhibiton on renal function in both chronically and acutely stimulated renin system.
Therefore male volunteers received a low sodium diet (4 g sodium chloride per day) in combination with the ACE-inhibitor ramipril (10 mg per day) for one week in order to achieve chronic stimulation of the renin system. Additionally the renin system was acutely stimulated by intravenous injection of the loop diuretic furosmide (20 mg).
We found that compared to baseline the combination of low sodium diet with ramipril caused an about 8-fold increase in plasma renin activity (PRA). After furosemide injection a 30-fold increase in PRA was observed. These results were paralelled by the findings in plasma aldosteron levels and urinary excretion of aldosterone glucuronide. With regard to PRA COX-2 inhibition did not affect chronic stimulation of the renin system. However, acute stimulation of the renin system by furosemide was attenuated by COX-2 inhibition. Both chronic and acute stimulation of plasma aldosterone and aldosterone glucuronide levels were reversed by rofecoxib. Furthermore rofecoxib caused sodium retention and reduced urine volume after furosemide injection. In addition, in chronic and acute stimulaiton refecoxib led to a decrease in hematocrit values as a measure of fluid retention. There were no effects of COX-2-inhibition on creatinine clearance.
Therefore we conclude that in both chronic and acute stimulation of the renin system COX-2-derived prostanoids are required to maintane renal function und body fluid homeostasis. Thus using selective COX-2-inhibitors may be as harmful to kidney function as using non selective inhibitors of cyclooxygenase.