Hormones Signaling and Myocardial Ischemia

Abstract

Although hormones constitute an important component of the adaptive response of the hving organism to various stresses, their role in myocardial ischemia has not been adequately explored. However, recent research reveals that hormone signaling is of physiological relevance in the context of ischemia and reperfusion. Furthermore, hormones or hormones' analogs are suggested as potential therapeutic agents for treating heart diseases. ESTROGENSClinical observations have suggested a cardioprotective role for estrogens. Consistent with this notion are several experimental reports. Acute administration of 17p-estradiol before ischemia and at reperfusion is shown to increase functional recovery and reduce lactate dehydrogenase (LDH) release in perfused rat hearts from ovariectomized rats. This effect was associated with less intracellular Na"" and Ca^^ and a blunted reduction in pH^ Similarly, acute pre-ischemic administration of 17p-estradiol and not 17a-estradiol limited infarct size in an in vivo model of coronary artery occlusion and reperfusion in ovariectomized rabbits. This response was abrogated by the administration of ICI 182,780, an estrogen receptor antagonist^ However, in a canine model of coronary occlusion and reperfusion, although 17p-estradiol reduced infarct size and arrhythmias, the administration of ICI 182,780 did not abolish these effects. Pretreatment with 5-hydroxydecanoate, a mitochondrial K^^ channel blocker abrogated the estrogen infarct size limiting effect while blockade of sarcolemmal K^^ channel abolished the effect of estrogen on reperfusion ventricular arrhythmias^. In open-chest dogs, infarct size and reperfusion ventricular arrhythmias were reduced by estrogen administration and this response was abrogated by inhibition of the NO synthase (NOS) or calcium-

Rebuilding the post-infarcted myocardium by activating ‘physiologic’ hypertrophic signaling pathways: the thyroid hormone paradigm

“…4) (unpublished observations). This response, unlike other hormones, was shown to be mediated by the suppression of the activation of the pro-apoptotic p38 MAPK and not by the upregulation of pro-survival signaling pathways [61]. Along this line, T3 administration in rats with myocardial infarction is found to reduce cardiac myocyte apoptosis in the border area of infarction [62].…”