Diminished natriuretic response to dopamine D1 receptor agonist, SKF-38393 in obese Zucker rats.
Dopamine causes natriuresis and diuresis via activation of D1 receptors located on the renal proximal tubules and subsequent inhibition of the sodium transporters, Na-H exchanger and Na+/K+ ATPase. We have reported that dopamine fails to inhibit the activities of these two transporters in the obese Zucker rats (OZR). The present study was designed to examine the functional consequence of this phenomenon by determining the natriuretic and diuretic response to D1 receptor activation in lean Zucker rats (LZR) and OZR. In 11-12 week-old OZR and LZR, natriuretic and diuretic responses to intravenously administered D1 receptor agonist, SKF 38393 (3 microg/kg/min for 30 min) were measured under Inactin anesthesia. Plasma insulin and glucose levels were significantly higher in the obese rats as compared to the lean rats. Intravenous infusion of SKF 38393 caused significant increases in urine flow, urinary sodium excretion (U(Na)V), fractional excretion of sodium (FE(Na)), and glomerular filtration rate (GFR) in the lean rats. However, the natriuretic and diuretic response to SKF 38393 was markedly blunted in OZR. Infusion of SKF 38393 did not cause significant changes in the mean blood pressure and heart rate in either of the two groups. We suggest that the diminished natriuretic response to D1 receptor activation in OZR is the consequence of the previously reported defect in the D1 receptor-G-protein coupling and the failure of dopamine to inhibit the sodium transporters in these animals.
Marwaha
Aditi
A
Heart and Kidney Institute, College of Pharmacy, University of Houston, Houston, Texas 77204-5041, USA.
Lokhandwala
Mustafa F
MF
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism; D006946:Hyperinsulinism / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D009318:Natriuresis / Q000187:drug effects; D045283:Natriuretic Agents / Q000494:pharmacology*; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D012964:Sodium / Q000652:urine
D001786:Blood Glucose; D018491:Dopamine Agonists; D007328:Insulin; D045283:Natriuretic Agents; D017447:Receptors, Dopamine D1; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D012964:Sodium