The renal responses to a specific dopamine antagonist (cis-flupentixol) and its stereoisomer (trans-flupentixol), a weak dopamine antagonist, were examined during hydropenia and Ringer loading in anesthetized rats. During hydropenia glomerular filtration (GFR), absolute (UNaV), and fractional (FENa) sodium excretion rates were similar as were single-nephron filtration (SNGFR) and proximal tubular flow rate (VTF). After Ringer loading GFR, UNaV, and FENa increased in all groups, but the increments were less in the cis-flupentixol than in the control or trans-flupentixol group. SNGFR and VTF increased similarly in all groups. In another series of experiments Ringer loading was performed prior to drug administration. Perfusion pressure (PP) was decreased in trans-flupentixol rats by aortic constriction to control for cis-flupentixol-induced reduction in PP. UNAV and FENa were lower in the cis-flupentixol- than trans-flupentixol-treated rats at comparable PP and GFR. In conclusion, dopamine blockade attenuated the natriuresis of Ringer loading; the mechanism is uncertain but may be related to a tubular effect at a site beyond the proximal convoluted tubule and/or in deeper nephrons.
Three groups of anesthetized puppies 16.4 +/- 1.2 (group I), 29.6 +/- 1.6 (group II), and 49.8 +/- 2.5 (group III) days of age were used to assess the renal response to graded doses of dopamine infusion into the renal artery. Dopamine infusion at 1 microgram X kg-1 X min-1 increased renal blood flow (RBF) from 3.61 +/- 0.31 to 4.22 +/- 0.43 ml X min-1 X g kidney wet wt-1 (P less than 0.05) only in the older puppies (group III). Glomerular filtration rate (GFR) increased in groups II and III from control values of 0.69 +/- 0.14 and 0.61 +/- 0.08 to 1.08 +/- 0.19 and 0.83 +/- 0.05 ml X min-1 X g kidney wet wt-1, respectively (P less than 0.05). However, urinary flow rate and sodium excretion were variably affected. Because dopamine is known to stimulate both alpha- and beta-adrenoceptors in addition to dopamine receptors, two additional groups of puppies 11.2 +/- 1.2 (group IV) and 72.8 +/- 2.4 (group V) days of age were studied to evaluate the renal effects of dopamine during the continuous intrarenal infusion of phentolamine and nadolol (an alpha- and a beta-adrenergic blocker, respectively). Dopamine elicited increases in RBF only in the older puppies (P less than 0.05). GFR, urinary flow rate, and sodium excretion increased in both groups; however, the magnitude of the change was greater for each parameter in the older group (P less than 0.05). These experiments suggest a maturational process for specific dopamine receptors and/or effector response, which may affect the observed age-dependent increases in RBF, GFR, and renal sodium handling.
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