AJP - Renal Physiology, Vol 262, Issue 6 1055-F1060, Copyright © 1992 by American Physiological Society
Dopamine DA1 receptor agonist, fenoldopam, reverses glycine-induced hyperfiltration in rats
Y. X. Wang, M. Gellai and D. P. Brooks
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.
Stimulation of dopamine DA1 receptors can prevent glomerular
hyperfiltration in streptozotocin-induced diabetic rats. In the present
study we have therefore investigated whether the DA1 agonist, fenoldopam,
can prevent glycine-induced hyperfiltration. Glomerular filtration rate
(GFR) and effective renal plasma flow (ERPF) were measured by inulin and
p-aminohippurate clearances in conscious chronically instrumented rats.
Glycine (3.7 mg/min iv; n = 8) significantly increased GFR by 37% (from
1.09 +/- 0.53 to 1.49 +/- 0.11 ml.100 g-1.min-1, P less than 0.01), ERPF by
23% (from 2.96 +/- 0.30 to 3.64 +/- 0.43 ml.100 g-1.min-1, P less than
0.05), and filtration fraction (FF) by 13% (from 0.39 +/- 0.04 to 0.44 +/-
0.05, P less than 0.05). Fenoldopam, at a dose (1 microgram.kg-1.min-1 iv;
n = 8) that increased ERPF by 26%, decreased FF by 13%, but did not change
GFR, significantly attenuated the glycine-induced hyperfiltration. In the
presence of fenoldopam, glycine resulted in only an 8% increase in GFR
(from 1.08 +/- 0.07 to 1.17 +/- 0.09 ml.100 g-1.min-1; n = 8). ERPF
increased by 20% (from 3.34 +/- 0.24 to 4.00 +/- 0.21 ml.100 g-1.min-1, P
less than 0.05), and FF decreased by 13% (from 0.34 +/- 0.03 to 0.29 +/-
0.02, P less than 0.05). Infusion of the DA1-selective antagonist, Sch
23390, abolished the effects of fenoldopam. Thus DA1 receptor activation
can prevent glomerular hyperfiltration induced by glycine.
