A STUDY ON THE EFFECT OF ESTROGEN ON THE CARDIOVASCULAR RESPONSIVENESS TO ADRENOCEPTORS STIMULATORS IN EXPERIMENTAL ANIMALS

SUMMARY AND CONCLUSIONIt is was found that women are less prone to ischemic heart diseases than men and that postmenopausal women with estrogen replacement therapy are less likely to develop ischemic heart diseasesThere is strong evidence that estrogen exerts a direct effect on the cardiovascular system, since estrogen receptors have been found in the heart, vascular smooth muscle and endothelium both in humans and in animals, providing strong biological evidence that the cardiovascular system is one of the targets of estrogen. Estrogen acts on blood vessels and hearts through a variety of genomic and nongenomic mechanisms.ARs are widely distributed in cardiovascular system and they are very important modulators for its functions. Many studies have focused on the effects of estrogen on different ARs (1, 2, 1, and 2). However, there is a wide controversy in this field. Also, the role of 3 ARs in cardiovascular system still unclearHence, it was decided to investigate the effect of estrogen on cardiac and vascular ARs responses to adrenergic stimulators in isolated perfused hearts and thoracic aortic strips in guinea pigs with a special speculation on the demonstration of the effect of 3 ARs stimulation and also the effect of estrogen on cardiac and vascular 3 ARs responses.Our protocol in this study was done on a total number of 90 adult healthy female guinea pigs. The animals were divided into three groups, each group consists of 30 animals: the first is sham operated control group, the second ovariectomized group, the third is Estrogen treated ovariectomized group. Then each group was subdivided into 5 equal subgroups, each subgroup consists of 6 animals, according to the type of the receptor examined: α1 AR group by Phenylephrine as a selective agonist, α2 AR group by Clonidine as a selective agonist, β1 AR group by Dobutamine as a selective agonist, β2 AR group by Salbutamol as a selective agonist, β3 AR group by Norepinephrine after addition of Propranolol to block β1 and β2 ARs and Phentolamine to block α1 and α2 ARs sparing β3 We examined the effects of these drugs on isolated heart preparations and isolated spiral aortic strips.The results of present study were as following:Concerning cardiac α1 and α2 ARs, stimulation of these receptors produced a significant dose dependent decrease in heart rate, increase in the amplitude of contraction, and decrease in coronary flow rate and positive correlation was found between the dose of Phenylephrine used and these responses. On these α1 and α2 ARs mediated responses, estrogen insignificantly decreased chronotropic and coronary flow rate responses but significantly decreased the amplitude of contraction.Concerning cardiac  and  ARs, stimulation of these receptors produce a significant dose dependent increase in heart rate, increase in the amplitude of contraction and decrease in coronary flow rate and positive correlation was found between the dose of Dobutamine used and these responses. On these  and  ARs mediated responses, estrogen insignificantly decreased the chronotropic and significantly decreased the inotropic responses and coronary flow rate in higher concentrations.Concerning cardiac  ARs,  ARs stimulation produces no significant change in heart rate, a significant decrease in the amplitude of contraction and a significant increase in coronary flow rate. On these  ARs mediated responses, ovariectomy did not affect the chronotropic response, significantly decreased the inotropic response and significantly decreased coronary flow rate compared to control and estrogen treated ovariectomized groups.Concerning vascular α1 ARs, it was found that there were positive correlations between the dose of Phenylephrine used and the amplitude of contraction produced. Estrogen significantly reduced the contractile response of aortic strips to Phenylephrine.Concerning vascular α2 ARs, it was found that selective ARs agonist (Clonidine) in the doses used has no contractile response.Concerning vascular and  ARs, it was found that there were positive correlations between the dose of Drug used and the % of reduction of amplitude of precontraction and Estrogen significantly increased the and  ARs relaxant effects on isolated aortic strips.We conclude that the effects of estrogen on cardiovascular ARs are differential according to the type and the site of the receptor. Our results show that in isolated guinea pig hearts, estrogen attenuate scardiac1 and 2 adrenergic responses more than that of cardiac 1 and 2.Cardiac  ARs stimulation produces no significant change in heart rate, a significant decrease in the amplitude of contraction and a significant increase in coronary flow rate.The suppressant effect of estrogen on cardiac 1 and 2 ARs responses and its enhancement effect on 3 mediated increase in coronary flow rate add beneficial effect to the estrogen in treatment of ischaemic heart disease. Moreover, 3 selective agonist can be used with care in ischaemic heart disease.In thoracic aorta, estrogen attenuated 1 ARs pressor responses however; it augmented 1, 2 and 3 adrenergic relaxant responses.Furthermore, estrogen attenuation of vascular 1 adrenergic responses and enhancement of vascular 1, 2 and 3 adrenergic responses can be used in treatment of certain vascular diseases such as hypertension and Raynaud’s disease.