EUKALIURIC NATRIURESIS AND DIURESIS IN RESPONSE TO DISPROCYNIUM24 - STUDIES ON THE TUBULAR SITE OF ACTION

We previously described that 1.1'-diisopropyl-2,4-cyanine (disprocyniu m24, DP24) exerts an eukaliuric diuresis and natriuresis in the anesth etized rat. The purpose of the present study was Co localize the tubul ar site of action of DP24. Employing micropuncture experiments in anes thetized rats, we first tested the effect of systemic application of D P24 (300 mu g/kg+300 mu g/kg h, i.v.) on whole kidney excretion rates as well as on fluid, sodium and potassium ion delivery to the early di stal tubule (V-ED, Na-ED(+), K-ED(+)), It was found that the eukaliuri c diuresis and natriuresis in response to DP24 was accompanied by a su bstantial increase in V-ED and Na-ED(+), suggesting a predominant tubu lar site of action upstream to the early distal tubule, most likely in the proximal tubule. DP24 caused a comparable fractional, although mi nor absolute increase in K-ED(+) as compared to Na-ED(+). Second, appl ication of DP24 into the first surface loop of the proximal tubule sig nificantly increased V-ED and Na-ED(+) at a concentration of about 10( -7) M, indicating that DP24 may act from the intratubular site, Third, microperfusion of tubular segments revealed that effects of DP24 on t he proximal convoluted tubule and the loop of Henle accounted for abou t 70 and 30%, respectively, of its diuretic and natriuretic action ups tream to the early distal tubule. With regard to the loop of Henle. th e quantitative effect of DP24 on fluid and Na+ reabsorption proposed a predominant effect on the straight part of the proximal tubule rather than the thick ascending limb. Intrabular DP24 did not affect reabsor ption in the distal tubule. In summary, the preset-It findings indicat e that: (1) the diuretic and natriuretic effect of DP24 resides predom inantly in the proximal tubule, and (2) DP24 may act fi-om the intratu bular site. Since DP24 increased V-ED and Na-ED(+) without apparently affecting sodium or potassium ion transport in the distal tubule. the mechanism of the eukaliuric response remains unclear.