Substance P-induced changes in kidney function in the conscious rat: relation to the renal prostaglandin system

Infusion of substance P into the renal artery was previously shown to cause a significant natriuresis which was associated with increased kallikrein excretion. Since the renal kinin and prostaglandin (PG) systems may be interrelated, the present study was performed to investigate the effects of substance P on renal function and its potential interaction with the renal PG system in the conscious rat. 24 female Sprague-Dawley rats were infused intravenously with substance P (1 ng . min-1 . kg-1 body weight) and the body weight was kept constant by an intravenous infusion of 0.45% saline. Substance P had no effects on arterial blood pressure, glomerular filtration rate (GFR) and 125I-hippuran clearance in the absence or presence of indomethacin (INDO). Basal UPGE2 V was unaltered by substance P infusion but was suppressed by INDO before and during substance P by 80 and 88%, respectively. Substance P raised urinary flow rate (V) by 105%, CH2O by 96%, UNaV by 378%, UKV by 48% and UPO4V by 147% (p less than 0.001). Although INDO significantly suppressed V, CH2O, and UNaV during all collection periods, it did not affect absolute UPO4V and UKV and the relative rise in V, CH2O, and UNaV induced by substance P. Thus, the diuretic and natriuretic effects of substance P are not mediated by renal PG, but are partially blunted by INDO through increased distal absorption of sodium and water, INDO has no effect on substance P-induced alterations in proximal tubular function.