EFFECT OF PROSTAGLANDIN SYNTHESIS INHIBITION ON MACULA DENSA-STIMULATED RENIN SECRETION

The purpose of the present studies was to evaluate directly the role o f prostaglandins in macula densa-mediated renin release. Individual ju xtaglomerular apparatus specimens were microdissected from rabbit kidn ey and perfused with a solution containing either high NaCl (Na+ = 141 meq/l; Cl- = 122 meq/l) or low NaCl (Na+ = 26 meq/l; Cl- = 7 meq/l) c oncentration. With a step decrease in perfusate NaCl (high to low), re nin secretion rate was markedly stimulated (from 15.06 to 63.1 nGU/min , P < 0.01), and the response was almost fully reversible. When specim ens were bathed with cyclooxygenase inhibitors flurbiprofen (10(-5)M) or flufenamic acid (10(-4)M), this macula densa-activated increase in renin release was largely or completely abolished (flurbiprofen, 3.5-1 0.5 nGU/min, not significant; flufenamic acid, 9.0-12.3 nGU/min, not s ignificant). Exposing the macula densa to a step increase in perfusate NaCl concentration (low to high) resulted in a significant and revers ible suppression of renin secretion in control specimens, but no signi ficant suppression was seen in specimens treated with flufenamic acid. These data provide direct evidence to support the hypothesis that loc ally produced prostaglandins may act as a primary mediator of the reni n response to macula densa activation.