We investigated the gender differences in heme-oxygenase (HO) enzyme, which produces endogenous vascular protective carbon monoxide (CO). We studied (1) the activity and expression of HO enzymes in the left ventricle (LV) and aorta, (2) basal increase in basal blood pressure provoked by arginine vasopressine (AVP) in vivo, (3) the heart perfusion induced by AVP, (4) the ST segment depression provoked by adrenaline and 30 seconds later phentolamine, and (5) the aorta ring contraction induced by AVP in female and male Wistar rats. We found that HO activity and the expression of HO-1 and HO-2 were increased in female rat aorta and LV. We demonstrated that the basal blood pressure and administration of AVP provoked blood pressure response are increased in the males; the female myocardium was less sensitive towards angina. Both differences could be aggravated by the inhibition of HO. The aorta rings were more susceptible towards vasoconstriction by AVP in males; isolated heart perfusion decrease was higher in males. The HO inhibition aggravated the heart perfusion in both sexes. In conclusion, the increased HO activity and expression in females might play a role in the sexual dimorphism of cardiovascular ischemia susceptibility during the reproductive age. 1. Introduction Gender-based differences in the incidence of hypertensive and coronary artery disease, the development of atherosclerosis, and myocardial remodelling after infarction are attributable to the direct effect of oestrogen on the myocardium, vascular smooth muscle (VSM), and endothelium. Cardiovascular morbidity and mortality are far less in premenopausal women compared to age-matched men, but the basis of this discrepancy remains controversial. Ovarian hormones are believed to be mainly responsible for this “female advantages” in cardiovascular function although the underlying mechanism has not been fully elucidated. In the heart and vasculature oestrogen mediates rapid vasodilation via production of nitric oxide (NO), protects against neointimal injury in the balloon-injured rat and facilitates the re-endothelialization of the damaged vessel [1], reduces both myocardial infarct size and occurrence of ischemia- and reperfusion-induced ventricular arrhythmias in canine heart [2]. Carbon monoxide (CO) is a product of heme oxygenase (HO) as well and is not an antioxidant but can cause induction of antioxidant genes [3–5]; it also decreases superoxide ( ) levels [6, 7], increases gluthione (GSH) levels [8], and has an antiapoptotic effect [9, 10]. Further, CO is a vasodilator, which has been shown
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