Effect of nolomirole on monocrotaline-induced heart failure

Pasini Evasio, Cargnioni Anna, Pastore Fiorella, Razzetti Roberta, Bongrani Stefano, Gitti Gian Luca, Ferrari Roberto

Research output: Contribution to journalArticlepeer-review

Abstract

Neurohormonal activation has been shown to be a major factor in congestive heart failure progression and mortality. The beneficial effects obtained in clinical trials with angiotensin converting enzyme (ACE) inhibitors, β-blockers and aldosterone antagonists have confirmed this hypothesis. 5,6-Diisobutirroyloxy-2-methyl-aminotetraline hydrochloride (nolomirole) is a selective agonist of prejunctional D2-dopaminergic and α 2-adrenergic receptors. The stimulation of these receptors inhibits catecholamine release from sympathetic nerve endings. To confirm that this mechanism can be useful in congestive heart failure, we studied the effects of nolomirole on monocrotaline-induced congestive heart failure. The ACE inhibitor trandolapril was used as reference compound. Rats were given single intraperitoneal injection of either saline (control group; n=20) or monocrotaline (50mgkg-1). Three days later, the monocrotaline- treated animals were randomly allocated (n=50 per group) to oral treatment with distilled water (vehicle group), nolomirole (0.25mgkg-1) twice a day, or trandolapril (0.3mgkg-1) once a day up to sacrifice. On the fourth week after monocrotaline injection, animals with signs of congestive heart failure were sacrificed for evaluation of heart hypertrophy and neuroendocrine alterations. Atrial natriuretic peptide (ANP) and alderosterone were determined by radioimmunoassay in plasma. Tissue norepinephrine concentration was quantified by high-pressure liquid chromatography. Nolomirole and trandolapril significantly reduced (a) hypertrophy of right atria and ventricles, (b) plasma levels of ANP and presence of pleural/peritoneal effusions and (c) norepinephrine depletion of right ventricle. These findings confirmed that nolomirole, like trandolapril, is able to attenuate the heart failure signs in the monocrotaline-induced congestive heart failure model.

Original languageEnglish
Pages (from-to)1-5
Number of pages5
JournalPharmacological Research
Volume49
Issue number1
DOIs
Publication statusPublished - Jan 2004

Keywords

  • D/α agonist
  • Monocrotaline-induced heart failure
  • Nolomirole
  • Trandolapril

ASJC Scopus subject areas

  • Pharmacology

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