possible role of calcitonin gene-related peptide in estradiol cardioprotection in cases of isoproterenol-induced myocardial ischemia in rats

ABSTRACT

Relative to its metabolic requirements, heart tissue is one of the most poorly perfused in the body, and ischemia resulting from compromised coronary blood flow can have serious detrimental effects. Estrogen has been suggested to modulate vascular physiology and function from a variety of studies in cellular, animal and human models. Genetic deletion of estrogen receptor results in the development of hypertension in middle-aged male and female mice, resulting in endothelial dysfunction and oxidative stress. Calcitonin gene-related peptide [CGRP], a well characterized vasoactive neuropeptide, is a 37 amino acid peptide resulting from the specific maturation processes of calcitonin gene products. It was discovered in 1982. CGRP is considered to be a neuromediator of particular importance in the cardiovascular system. Regardless of which estrogen receptor mediates cardioprotection, the mechanisms by which estrogen elicits cardioprotection in females are poorly understood. Hence, the present study was conducted in order to investigate the possible role of CGRP in cardioprotection offered by estradiol pretreatment in cases of isoproterenol-induced myocardial ischemia in rats. The present study was conducted on 24 adult female albino rats, weighing 150-200 gms, fed ad libitum, divided into 3 groups Group [I] 8 sham-operated rats that served as control. Group [II] 8 rats that underwent ovarectomy [day 0] and 7 days later, they were pretreated with estradiol subcutaneously [0.25 mg/kg] for 21 day period. Group [III] 8 rats that also underwent ovarectomy but stayed without estradiol treatment for 28 days. Group II and III rats were, thereafter, intoxicated with isoproterenol subcutaneously [85 mg/kg] for 2 consecutive days to induce myocardial ischemia. Then, all rats were killed. Blood was collected and serum was assayed for blood lipids, creatine kinase and lactate dehydrogenase activities, serum CGRP was also measured. Heart tissues were homogenized and estimation of cardiac CGRP was done. Serum creatine kinase and lactate dehydrogenase activities were significantly increased in group III rats as compared to group I and II. Serum triglycerides and total cholesterol levels also showed a significant increase in group III rats as compared to group I and II. Serum and cardiac CGRP were significantly increased in group II [estradiol-pretreated rats] as compared to group I and III. Significant positive correlation was found between serum and cardiac levels of CGRP, also between both and serum triglycerides. From the previous results, we can conclude that estradiol may exert a protective effect in cases of isoproterenol-induced myocardial ischemia in rats through increasing serum and cardiac levels of CGRP, decreasing serum lactate dehydrogenase and creatine kinase activities and lowering serum triglycerides and total cholesterol levels as compared to estradiol-untreated rats