CHF-1024, a DA(2)/alpha(2) agonist, blunts norepinephrine excretion and cardiac fibrosis in pressure overload

We compared the effects of an ACE inhibitor, captopril, with those of a DA( 2)-dopaminergic/alpha (2)-adrenergic receptor agonist (CHF-1024) on neuroen docrine activation and cardiac fibrosis in a model of pressure-overload hyp ertrophy. Interrenal aortic stenosis was performed in 89 rats, treated with CHF-1024 (0.33, 2 or 6 mg kg(-1) day(-1)), or captopril (1 g/L). Hemodynam ic variables were recorded. Cardiac and renal weights, plasma aldosterone, renin activity and urinary catecholamine excretion were measured, as well a s cardiac collagen. Blood pressure was lower in stenotic animals treated wi th CHF-1024 compared to vehicle (161 +/- 10 vs 219 +/- 10 mmHg, p < 0.01), but LV weight was similar. CHF-1024 elicited a marked dose-dependent attenu ation of urinary norepinephrine excretion (1.80 +/- 0.18 in controls compar ed to 0.40 +/- 0.14 <mu>g/24 h at the highest dose, p < 0.01) and of LV per ivascular fibrosis. Captopril provoked a marked hypotension, reduced cardia c and body weights, plasma aldosterone concentration, dopamine excretion an d perivascular collagen. The DA(2)/<alpha>(2) agonist CHF-1024 effectively blunts adrenergic drive and cardiac fibrosis in a rat model of pressure ove rload.