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Effects of treatment with a 5-HT4 receptor antagonist in heart failure.
Birkeland, J A K; Sjaastad, I; Brattelid, T; Qvigstad, E; Moberg, E R; Krobert, K A; Bjørnerheim, R; Skomedal, T; Sejersted, O M; Osnes, J-B; Levy, F O.
Afiliação
  • Birkeland JA; Institute for Experimental Medical Research, University of Oslo, Oslo, Norway.
Br J Pharmacol ; 150(2): 143-52, 2007 Jan.
Article em En | MEDLINE | ID: mdl-17160012
ABSTRACT
BACKGROUND AND

PURPOSE:

Positive inotropic responses (PIR) to 5-hydroxytryptamine (5-HT) are induced in the left ventricle (LV) in rats with congestive heart failure (CHF); this is associated with upregulation of the G(s)-coupled 5-HT(4) receptor. We investigated whether chronic 5-HT(4) receptor blockade improved cardiac function in CHF rats. EXPERIMENTAL

APPROACH:

Rats were given either the 5-HT(4) antagonist SB207266 (0.5 mg kg(-1) 24h(-1); MI(int)) or placebo (MI(pl)) through mini-osmotic pumps for 6 weeks subsequent to induction of post-infarction CHF. In vivo cardiac function and ex vivo responses to isoprenaline or 5-HT were evaluated using echocardiography and isolated LV papillary muscles, respectively. mRNA levels were investigated using real-time quantitative RT-PCR. KEY

RESULTS:

LV diastolic function improved, with 4.6% lower LV diastolic diameter and 24.2% lower mitral flow deceleration in MI(int) compared to MI(pl). SB207266 reduced LV systolic diameter by 6.1%, heart weight by 10.2% and lung weight by 13.1%. The changes in posterior wall thickening and shortening velocity, cardiac output, LV systolic pressure and (dP/dt)(max), parameters of LV systolic function, did not reach statistical significance. The PIR to isoprenaline (10 microM) increased by 36% and the response to 5-HT (10 microM) decreased by 57% in MI(int) compared to MI(pl). mRNA levels for ANP, 5-HT(4(b)) and 5-HT(2A) receptors, MHCbeta, and the MHCbeta/MHCalpha -ratio were not significantly changed in MI(int) compared to MI(pl). CONCLUSIONS AND IMPLICATIONS Treatment with SB207266 to some extent improved in vivo cardiac function and ex vivo myocardial function, suggesting a possible beneficial effect of treatment with a 5-HT(4) receptor antagonist in CHF.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piperidinas / Antagonistas do Receptor 5-HT4 de Serotonina / Insuficiência Cardíaca / Indóis Limite: Animals Idioma: En Revista: Br J Pharmacol Ano de publicação: 2007 Tipo de documento: Article País de afiliação: Noruega

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piperidinas / Antagonistas do Receptor 5-HT4 de Serotonina / Insuficiência Cardíaca / Indóis Limite: Animals Idioma: En Revista: Br J Pharmacol Ano de publicação: 2007 Tipo de documento: Article País de afiliação: Noruega