Experimental and clinical approaches to treatment of hypertension by dopamine receptor agonists

The action of several dopamine agonists on blood pressure was investigated. In dogs, apomorphine induced a decrease in blood pressure and an increase in heart rate. These effects were suppressed by intravenous haloperidol or phentolamine. Intravenous but not intracisternal domperidone suppressed the hypotensive responses elicited by intravenous or intracisternal apomorphine. Furthermore, the hypotensive effect of bromocriptine or apomorphine was abolished in adrenal demedullated dogs. Apomorphine and bromocriptine decreased adrenal catecholamine levels. In men, the acute hypotensive property of apomorphine (but not the long term effect of bromocriptine) was suppressed by pretreatment with domperidone. In hypertensive Parkinsonians, bromocriptine reduced blood pressure, induced an increase in inulin clearance, a decrease in plasma creatinine concentration and in renal vascular resistances. These results suggest that dopamine agonists (like apomorphine or bromocriptine) reduce blood pressure through both a decrease in sympathetic tone and an improvement in renal function. However, the mechanism of the acute and long term hypotensive effects could be different only involving peripheral mechanisms after acute administration and both peripheral and central structure under chronic treatment. In addition, preliminary results suggesting the potential interest of dopamine antagonists in the management of orthostatic hypotension are discussed.