Enhanced response to the inhibitory action of LY171555, a dopamine D2-agonist, on in vivo striatal dopamine release in DOCA/NaCl-hypertensive rats

Abstract

Our previous studies have demonstrated that LY171555 (quinpirole), a specific dopamine (DA) D2-receptor agonist, has a pressor effect in the conscious rat which is accompanied by increased sympathetic outflow and arginine vasopressin release. To test the hypothesis that LY171555 inhibits in vivo release of DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), from central dopaminergic neurons of the conscious, freely moving rat by activation of presynaptic DA receptors in the central nervous system and that this mechanism may be altered in the desoxycorticosterone acetate (DOCA)/NaCl model of hypertension, we used the in vivo push-pull perfusion method to study the effect of LY171555 on central DA release in normotensive and DOCA/NaCl-hypertensive rats. Levels of the DOPAC and HVA were measured in striatal perfusates by HPLC before and after administration of LY171555 (1 mg/kg, i.v.) of conscious, unrestrained 4-week DOCA/NaCl hypertensive and uninephrectomized H2O control rats. There were no significant differences in basal striatal HVA (80 +/- 12 vs 89 +/- 11 pg/min; DOCA/NaCl vs control) or DOPAC levels (37 +/- 5 vs 49 +/- 17 pg/min; DOCA/NaCl vs control) during the entire 240-min collection period. LY171555 significantly reduced HVA and DOPAC levels in perfused striatum in both normotensive control and DOCA/NaCl-hypertensive rats. The LY171555-induced suppression in HVA levels was significantly greater in DOCA/NaCl rats (delta = 60.7 +/- 3.6%) than in H2O controls (delta = 49.0 +/- 3.5%, P less than 0.05). Pretreatment with metoclopramide (10 mg/kg, i.v.), a specific central and peripheral DA D2-receptor antagonist, completely blocked the suppressive effects of LY171555 on HVA and DOPAC levels.(ABSTRACT TRUNCATED AT 250 WORDS)