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CHF-1024, A DA2/α2 Agonist, Blunts Norepinephrine Excretion and Cardiac Fibrosis in Pressure Overload

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Abstract

We compared the effects of an ACE inhibitor, captopril, with those of a DA2-dopaminergic/α2-adrenergic receptor agonist (CHF-1024) on neuroendocrine activation and cardiac fibrosis in a model of pressure-overload hypertrophy. 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). Hemodynamic variables were recorded. Cardiac and renal weights, plasma aldosterone, renin activity and urinary catecholamine excretion were measured, as well as cardiac collagen. Blood pressure was lower in stenotic animals treated with 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 attenuation of urinary norepinephrine excretion (1.80 ± 0.18 in controls compared to 0.40 ± 0.14 μg/24 h at the highest dose, p < 0.01) and of LV perivascular fibrosis. Captopril provoked a marked hypotension, reduced cardiac and body weights, plasma aldosterone concentration, dopamine excretion and perivascular collagen. The DA2/α2 agonist CHF-1024 effectively blunts adrenergic drive and cardiac fibrosis in a rat model of pressure overload.

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Authors and Affiliations

  1. Department of Cardiovascular Research, Istituto di Ricerche Farmcologiche, “Mario Negri”

    Serge Masson, Stefano Chimenti, Monica Salio, Mauro Torri, Federica Limana, Roberto Bernasconi, Laura Calvillo & Roberto Latini

  2. Department of Internal Medicine and Geriatrics, Milan University and IRCCS Ospedale Maggiore, Milan

    Daniela Santambrogio, Nicoletta Gagliano, Beatrice Arosio & Giorgio Annoni

  3. Chiesi Farmaceutici, Parma, Italy

    Roberta Razzetti & Stefano Bongrani

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  1. Serge Masson
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  2. Stefano Chimenti
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Masson, S., Chimenti, S., Salio, M. et al. CHF-1024, A DA2/α2 Agonist, Blunts Norepinephrine Excretion and Cardiac Fibrosis in Pressure Overload. Cardiovasc Drugs Ther 15, 131–138 (2001). https://doi.org/10.1023/A:1011170812267

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