REDUCTION OF PLASMA-RENIN ACTIVITY BY INHIBITION OF THE FATTY-ACID CYCLOOXYGENASE IN HUMAN-SUBJECTS - INDEPENDENCE OF SODIUM RETENTION

The authors carried out the present studies to determine whether the suppression of plasma renin activity (PRA) that follows inhibition of prostaglandin (PG) synthesis can be dissociated from the sodium-retaining effects of these drugs. In an initial investigation they studied tha effect of indomethacin on PRA in normal subjects in balance on a 10 mM Na+ diet to prevent Na+ retention. Under these experimental conditions indomethacin did not lower PRA even though the fatty acid cyclooxygenase was inhibited, as indicated by a >70% reduction in the major urinary metabolite of prostaglandin E (PGE-M). Sodium depletion leads to enhanced sympathetic activity. They therefore studied the effect of indomethacin on a group of subjects in 10 mM Na+ balance in whom the effect of increased β-sympathetic suppression of PGE-M and had no effect on Na+ balance, but reversibly reduced PRA in the supine and upright positions by 84% and 70%, respectively. In normal subjects in 10 mM Na+ balance, the isoproterenol-induced increase in PRA also was unaffected by indomethacin. These data establish that inhibition of the cyclooxygenase can result in a reduction of PRA that is independent of changes in Na+ balance or β-sympathetic tone.