Deficiency of sex hormones does not affect 17-ß-estradiol-induced coronary vasodilation in the isolated rat heart

Abstract

The relaxation of coronary arteries by estrogens in the coronary vascular beds of naive and hypertensive rats has been well described. However, little is known about this action in gonadectomized rats. We investigated the effect of 17-ß-estradiol (E2) in coronary arteries from gonadectomized rats, as well as the contributions of endothelium-derived factors and potassium channels. Eight-week-old female and male Wistar rats weighing 220-300 g were divided into sham-operated and gonadectomized groups (n=9−12 animals per group). The baseline coronary perfusion pressure (CPP) was determined, and the vasoactive effects of 10 μM E2 were assessed by bolus administration before and after endothelium denudation or by perfusion with NG-nitro-L-arginine methyl ester (L-NAME), indomethacin, clotrimazole, L-NAME plus indomethacin, L-NAME plus clotrimazole or tetraethylammonium (TEA). The CPP differed significantly between the female and sham-operated male animals. Gonadectomy reduced the CPP only in female rats. Differences in E2-induced relaxation were observed between the female and male animals, but male castration did not alter this response. For both sexes, the relaxation response to E2 was, at least partly, endothelium-dependent. The response to E2 was reduced only in the sham-operated female rats treated with L-NAME. However, in the presence of indomethacin, clotrimazole, L-NAME plus indomethacin or L-NAME plus clotrimazole, or TEA, the E2 response was significantly reduced in all groups. These results highlight the importance of prostacyclin, endothelium-derived hyperpolarizing factor, and potassium channels in the relaxation response of coronary arteries to E2 in all groups, whereas nitric oxide may have had an important role only in the sham-operated female group.

Pomegranate Extract Enhances Endothelium-Dependent Coronary Relaxation in Isolated Perfused Hearts from Spontaneously Hypertensive Ovariectomized Rats

“…Hormonal dysfunction in OVX females is an important factor to the development of hypertension and coronary artery disease because the presence of estrogen is able to modulate the NO synthesis by acting on the isoforms of the enzyme nitric oxide synthase (NOS). Indeed, results from our laboratory indicate that the main endothelial mediator responsible for regulating the coronary vascular tone (represented by the baseline CPP) is the NO in both Wistar and SHR rats (Santos et al, 2004, 2010, 2016). Therefore, ovariectomy leads to damages on the endothelial function, as previously showed by our study group (Borgo et al, 2011; Caliman et al, 2013; Claudio et al, 2013; Oliveira et al, 2014; Lamas et al, 2015); impairing thus, the preventive/therapeutic effects from the PHE on the baseline CPP values in the OVX-PHE group.…”

“…Besides its scavenger effect, we have previously shown that pomegranate is able to reduce the angiotensin-converting enzyme (ACE) activity (Santos et al, 2016) contributing to an environment with less oxidative stress consequently reducing CVDs risk (Aviram and Dornfeld, 2001; Mohan et al, 2010). In addition, with the ACE inhibition there is a decreasing in bradykinin degradation that may contribute to our results (Shiuchi et al, 2002).…”

GPER modulates tone and coronary vascular reactivity in male and female rats

“…(Moyses et al 2001) showed that oestrogen replacement in gonadectomized rats restores the baseline CPP in females and increases the CPP in males to become similar to those found in naive female animals. Indeed, a recent study from our group also showed that gonadectomy reduces the baseline CPP in females and has no effect on the baseline CPP of hearts from male rats (Santos et al 2016). Notably, even after gonadectomy, these differences in the CPP continued to exist between females and males, perhaps because the benefits of oestrogens on the coronary arteries were not completely lost after gonadectomy.…”

“…In our study, the acute administration of G-1 promoted vasodilation in the coronary vascular beds of isolated hearts from male and female rats. Our previous studies have already demonstrated that E2 is able to induce a relaxing response in the coronary vessel (Santos et al 2004(Santos et al , 2010(Santos et al , 2012(Santos et al , 2016. However, such actions could not be directly attributed to GPER, since oestradiol also acts on intracellular receptors (ERα and ERβ).…”

“…Therefore, we suggest that the higher basal tone found in female rats is due to oestrogen. Higher CPP could allow greater vasodilation, thus exerting cardioprotective effects when the supply of oxygen and nutrients are reduced (Santos et al 2016).…”