Sustained anti-β-adrenergic effect of melatonin in guinea pig heart papillary muscle

Abstract

Objective. Anti-β-adrenergic actions of several substances influence heart function significantly. The anti-β-adrenergic effect of melatonin was investigated, with special attention to protein kinase C (PKC) and nitric oxide (NO). Design. Guinea pig papillary muscles were exposed to melatonin (500 pM) for 15 min and 20 min washout. Contractile force was measured during a bolus of isoproterenol (300 nM) given before melatonin, at the end of melatonin-exposure and after washout. In separate experiments blockers of PKC, NO-synthase (NOS) and melatonin receptors were added, or forskolin (10 μM) substituted for isoproterenol. Results. Melatonin significantly reduced the increase in contractile force in response to isoproterenol, both when present and after melatonin-washout. The reduction was unaffected by inhibition of PKC, while inhibition of melatonin receptors or NOS seemed to abolish the effect. Melatonin induced a sustained but not acute reduction of contractile force response with forskolin stimulation. This was abolished by NOS-inhibition. Conclusion. Receptor-mediated immediate and sustained anti-β-adrenergic effects of melatonin were demonstrated in contractile function. A role for NO in the response was indicated, while a role for PKC was not verified. © 2006 Taylor & Francis.