Neurohumoral response to carmoxirole, a selective dopamine (D2) receptor agonist, in patients with chronic moderate heart failure.
Neurohormonal activation and elevated ventricular filling pressures are prominent features in heart failure. Carmoxirole is a DA2 receptor agonist with limited central activity that modulates sympathetic activation and subsequently reduces pre-load and afterload in animals. The effect of carmoxirole on neurohormones and hemodynamics in humans was evaluated in 12 normotensive patients with NYHA class III-IV heart failure on stable ACE 1 and diuretic therapy. Carmoxirole (0.25-1.00 mg) was administered on 2 consecutive days, and hemodynamic and neurohormonal measurements were carried out. Values given are maximal percent changes from prestudy baseline (significance level P < 0.05). The lower dose on day 1 (0.25-0.50 mg) reduced circulating norepinephrine, vasopressin, and ANP by 40%, 19%, and 25%, respectively. In addition, on day 2, at a dose level of 0.75-1.00 mg, plasma renin activity decreased by 30%. Mean arterial pressure and systemic vascular resistance were reduced by 10% and 18%, and pulmonary wedge and right atrial pressure by 38% and 39%, respectively. Cardiac index improved by 20%. Despite a concomitant 12% reduction in heart rate, both stroke volume and stroke work index increased by 32% and 31%, respectively. Mean pulmonary artery pressure decreased by 21%, whereas pulmonary resistance was not affected. Thus, carmoxirole modulates sympathetic activation, accompanied by changes in vasopressin and ANP, and the renin-angiotensin system at higher dosages. These effects lead to a reduction in systemic resistance and heart rate, and an improvement in cardiac pump function and left and right ventricular filling pressures. It is concluded that carmoxirole induces beneficial effects on hemodynamic and neurohumoral parameters in heart failure.
van der Ent
M
M
Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands.
van den Heuvel
A F
AF
Remme
W J
WJ
D000368:Aged; D009320:Atrial Natriuretic Factor / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002908:Chronic Disease; D018491:Dopamine Agonists / Q000494:pharmacology*; D004562:Electrocardiography; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D018377:Neurotransmitter Agents / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D014667:Vasopressins / Q000187:drug effects
D018491:Dopamine Agonists; D007211:Indoles; D018377:Neurotransmitter Agents; D011725:Pyridines; D017448:Receptors, Dopamine D2; D014667:Vasopressins; D009320:Atrial Natriuretic Factor; C071485:carmoxirole; D009638:Norepinephrine