THE EFFECT OF FENOLDOPAM ON THE BLOOD-PRESSURE OF THE RAT

1. Fenoldopam mesylate, a benzazepine derivative, is a D-1 receptor ag onist that lowers blood pressure through vasodilation of renal, mesent eric, coronary and cerebral vascular beds. 2. Experiments were perform ed in rats, and mean carotid blood pressure and heart rate were regist ered. Two series of experiments were performed: (1) fenoldopam as cont rol group and (2) fenoldopam after pretreatment with one of the follow ing drugs: the D-1 antagonist SCH 23390, the D-2 antagonist sulpiride, the selective beta(1)-adrenergic antagonist atenolol, the selective b eta(2)-adrenergic antagonist ICI 118,551, the nonselective beta-adrene rgic antagonist propranolol and the neurotoxin that destroys catechola minergic nerve terminals 6-hydroxydopamine (6-OH-DA). 3. Fenoldopam pr oduced a dose-dependent hypotensive effect that was not modified by pr etreatment of the rat with atenolol or propranolol; however, ICI 118.5 51 produced a significant reduction of the hypotensive response induce d by fenoldopam. 4. Pretreatment of the animals with SCH 23390 produce d a significant dose related reversal of the rat blood pressure reduct ion induced by low doses of fenoldopam. Sulpiride produced a result si milar to that induced by pretreatment with SCH 23390. 5. The pretreatm ent of the animals with B-OH-DA surprisingly attenuated the response i nduced by fenoldopam and produced only a significant reversal of the r eduction of mean blood pressure induced with the lower dose of fenoldo pam. 6. The findings obtained in the present work do not provide furth er evidence of direct participation of beta(2)-adrenergic receptors on the mechanism of action of fenoldopam. Its action seems to be mainly due to activation of D-1 cardiovascular receptors. (C) 1998 Elsevier S cience Inc.