Effect of progesterone-Carbachol derivative on perfusion pressure and coronary resistance in isolated rat heart: Via activation of the M₂ muscarinic receptor

Aim. The present study was designed to investigate the effects of progesterone-carbachol derivative on perfusion pressure and coronary resistance in rats. An additional aim was to identify the molecular mechanisms involved. Methods. The Langendorff model was used to measure perfusion pressure and coronary resistance changes in isolated rat heart after progesterone-carbachol derivative alone and after the following compounds; mifepristone (progesterone receptor blocker), yohimbine (α₂ adreno-receptor antagonist), ICI 118,551 (selective β₂ receptor blocker), atropine (non-selective muscarinic receptor antagonist), methoctramine (antagonist of M₂ receptor) and L-NAME (inhibitor of nitric oxide synthase). Results. The results show that progesterone-carbachol derivative [10^-9 mM] significantly decreased perfusion pressure (P=0.005) and coronary resistance (P=0.006) in isolated rat heart. Additionally, the effect of progesterone-carbachol on perfusion pressure [10^-9 to 10^-4 mM] was only blocked in the presence of methoctramine and L-NAME. Conclusions. These data suggest that progesterone derivative exert its effect on perfusion pressure via activation of the M₂ muscarinic. In addition, this phenomenon involves stimulation of nitric oxide synthase (NOS).