Concerted regulation of renal plasma flow and glomerular filtration rate by renal dopamine and NOS I in rats on high salt intake

Abstract

Under high sodium intake renal dopamine ( DA) increases while NOS I expression in macula densa cells ( MD) decreases. To explore whether renal DA and NOS I, linked to natriuresis and to the stability of the tubuloglomerular feedback, respectively, act in concert to regulate renal plasma flow ( RPF) and glomerular filtration rate ( GFR). Male Wistar rats were studied under a normal sodium intake ( NS, NaCl 0.24%) or a high sodium intake ( HS, NaCl 1% in drinking water) during the 5 days of the study. For the last two days, the specific D ₁‐like receptor antagonist SCH 23390 (1 mg kg bwt ⁻¹ day ⁻¹, sc) or a vehicle was administered. HS intake increased natriuresis, diuresis, and urinary DA while it decreased cortical NOS I expression ( P < 0.05 vs. NS), Nicotinamide adenine dinucleotide phosphate diaphorase ( NADPH‐d) activity in MD ( P < 0.001 vs. NS) and cortical nitrates+nitrites ( NOx) production ( NS 2.04 ± 0.22 vs. HS 1.28 ± 0.10 nmol mg protein ⁻¹, P < 0.01). Treatment with SCH 23390 to rats on HS sharply decreased hydroelectrolyte excretion ( P < 0.001 vs. HS) while NOS I expression, NADPH‐d activity and NOx production increased ( P < 0.05 vs. HS for NOS I and P < 0.001 vs. HS for NADPH‐d and NOx). SCH 23390 increased RPF and GFR in HS rats ( P < 0.01 HS+ SCH vs. HS). It did not cause variations in NS rats. Results indicate that when NS intake is shifted to a prolonged high sodium intake, renal DA through the D ₁R, and NOS I in MD cells act in concert to regulate RPF and GFR to stabilize the delivery of NaCl to the distal nephron.