Renal dopamine and sodium excretion.
In the present study, we examined the renal effects of a low dose of fenoldopam in pentobarbital anesthetized rats in an attempt to unmask a direct tubular DA-1 receptor mediated diuresis and natriuresis. We also performed experiments to determine the possible contribution of renal dopamine (DA) and DA receptors in the natriuretic response to acute sodium loading. Fenoldopam (0.5 microgram/kg/min) produced significant increases in urine output (UV) and urinary sodium excretion (UNaV) without altering mean blood pressure (MBP), renal blood flow (RBF) or heart rate (HR), suggesting a direct tubular site of action. This renal response to fenoldopam was completely abolished in the presence of the selective DA-1 receptor antagonist, SCH 23390. Isotonic NaCl loading (5% body weight for 1 h) enhanced urinary DA excretion (UDA V) which correlated significantly with the increase in UNa V. Pretreatment with selective DA-1 receptor antagonist SCH 23390 resulted in significant attenuation of the increase in UNa V whereas the increase in UDA V was unaltered. Pretreatment with selective DA-2 receptor antagonist domperidone did not alter the increase in UNa V during isotonic NaCl loading. These results suggest that renal tubules are endowed with DA-1 receptors activation which results in diuresis and natriuresis. Furthermore, activation of these DA-1 receptors but not DA-2 receptors by endogenous DA contributes to the natriuretic response to isotonic saline loading.
Hegde
S S
SS
Department of Pharmacology, University of Houston, TX 77204-5515.
Lokhandwala
M F
MF
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004231:Diuresis / Q000187:drug effects; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018818:Fenoldopam; D007552:Isotonic Solutions / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology
D007552:Isotonic Solutions; D012965:Sodium Chloride; D004294:Domperidone; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D018818:Fenoldopam; D004298:Dopamine