Abstract
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. 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). 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. 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).
Highlights
High blood pressure contributes substantially to cardiovascular disease incidence and premature mortality[1,2,3,4]
The results showed that progesterone-carbachol [10-9 mM] significantly decreased the perfusion pressure (P=0.005) in comparison with the control conditions and progesterone
Other results (Fig. 3) indicate that coronary resistance calculated as the ratio of perfusion pressure at the coronary flow assayed (10 ml/min) was low (P=0.006) in the presence of progesterone-carbachol derivative [10-9 mM] than in control conditions and progesterone
Summary
High blood pressure contributes substantially to cardiovascular disease incidence and premature mortality[1,2,3,4]. There are studies which have demonstrated higher incidence of hypertension in women after menopause[6] which suggests that female sex hormones protect against the development of hypertension. In this sense, there are studies which have shown that oral administration of natural progesterone significantly lowered blood pressure in six men and four postmenopausal women with mild to moderate hypertension who were not receiving antihypertensive drugs[7]. Administration of natural progesterone (200 mg, orally) to seven postclimacteric women failed to influence blood pressure[8]. Another study showed that increases in levels of progesterone were positively correlated with decreases in blood pressure in the progression of pregnancy[9]
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