Effect of pramipexole, a dopamine-1/dopamine-2 receptor agonist, on sodium excretion and blood pressure in spontaneously hypertensive rats.
1. Abnormalities of the renal dopaminergic system have been implicated in the pathogenesis of hypertension in the spontaneously hypertensive rat (SHR). 2. Both DA-1 and DA-2 receptors are present in renal tubules and blood vessels. DA-1 receptors mediate the renal vasodilatory and natriuretic effects of DA but the contribution of DA-2 receptors to these effects is not known. 3. We therefore studied the effect of a novel and selective DA-1 and DA-2 agonist, pramipexole, on MAP, glomerular filtration rate (GFR), urine flow (V), absolute (UNaV) and fractional sodium (FeNa) excretion in 9-18-week-old SHR. Wistar-Kyoto rats (WKY) served as control. 4. Pramipexole given intravenously (1, 10, 100 micrograms kg body wt-1 min-1) decreased MAP in a dose-related manner to a greater extent in SHR (n = 5) than WKY (n = 6) such that at the highest dose of pramipexole, MAP was similar in both groups. Pramipexole did not alter GFR in either WKY or SHR. Pramipexole increased V in a dose-related manner in both WKY and SHR. At 100 micrograms pramipexole kg body wt-1 min-1, V increased eightfold in both SHR and WKY. In contrast, pramipexole increased UNaV to a greater extent in WKY (5.1-fold) than SHR (3.7-fold). 5. These studies show a differential effect of pramipexole on renal function and MAP in SHR and WKY. Pramipexole has a more potent blood pressure lowering effect in SHR than in WKY. However, the natriuretic effect of pramipexole was greater in the WKY than in the SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
Kaneko
S
S
Department of Paediatrics, Kurume University School of Medicine, Japan.
Eisner
G M
GM
Jose
P A
PA
D000818:Animals; D052160:Benzothiazoles; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology; D000077487:Pramipexole; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013844:Thiazoles / Q000494:pharmacology*
D052160:Benzothiazoles; D015259:Dopamine Agents; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013844:Thiazoles; D000077487:Pramipexole