Endothelial mediators of 17ß-estradiol-induced coronary vasodilation in the isolated rat heart

Abstract

The present study was designed to determine relaxation in response to 17ß-estradiol by isolated perfused hearts from intact normotensive male and female rats as well as the contribution of endothelium and its relaxing factors to this action. Baseline coronary perfusion pressure was determined and the vasoactive effects of 17ß-estradiol (10 µM) were assessed by in bolus administration before and after endothelium denudation by infusion of 0.25 µM sodium deoxycholate or perfusion with 100 µM L-NAME, 2.8 µM indomethacin, 0.75 µM clotrimazole, 100 µM L-NAME plus 2.8 µM indomethacin, and 100 µM L-NAME plus 0.75 µM clotrimazole. Baseline coronary perfusion pressure differed significantly between males (84 ± 2 mmHg, N = 61) and females (102 ± 2 mmHg, N = 61). Bolus injection of 10 µM 17ß-estradiol elicited a transient relaxing response in all groups, which was greater in coronary beds from females. For both sexes, the relaxing response to 17ß-estradiol was at least in part endothelium-dependent. In the presence of the nitric oxide synthase inhibitor L-NAME, the relaxing response to 17ß-estradiol was reduced only in females. Nevertheless, in the presence of indomethacin, a cyclooxygenase inhibitor, or clotrimazole, a cytochrome P450 inhibitor, the 17ß-estradiol response was significantly reduced in both groups. In addition, combined treatment with L-NAME plus indomethacin or L-NAME plus clotrimazole also reduced the 17ß-estradiol response in both groups. These results indicate the importance of prostacyclin and endothelium-derived hyperpolarizing factor in the relaxing response to 17ß-estradiol. 17ß-estradiol-induced relaxation may play an important role in the regulation of coronary tone and this may be one of the reasons why estrogen replacement therapy reduces the risk of coronary heart disease in postmenopausal women.

Uso crônico de decanoato de nandrolona como fator de risco para hipertensão arterial pulmonar em ratos Wistar

“…Vários outros estudos têm demonstrado efeitos diretos e diferenciados dos hormônios sexuais endógenos e exógenos no sistema cardiovascular (29)(30)(31) . O estrogênio, por exemplo, está diretamente associado a efeito cardioprotetor, pela redução da resistência local e perifé-rica, pela modulação da hipertrofia de cardiomiócitos e de células de músculo liso vascular (CMLV), através do sistema renina-angiotensina cardíaco; ou ainda estimulando a formação de fatores vasodilatadores derivados do endotélio, como óxido nítrico e prostaciclinas.…”

“…O estrogênio, por exemplo, está diretamente associado a efeito cardioprotetor, pela redução da resistência local e perifé-rica, pela modulação da hipertrofia de cardiomiócitos e de células de músculo liso vascular (CMLV), através do sistema renina-angiotensina cardíaco; ou ainda estimulando a formação de fatores vasodilatadores derivados do endotélio, como óxido nítrico e prostaciclinas. Por outro lado, a testosterona está mais associada ao aumento da resistência vascular periférica, causado pela estimulação da angiotensina-II, que pode ocasionar a hipertrofia de CMLV, vasoconstrição ou, ainda, estimular outros fatores vasoconstritores derivados do endotélio, como a endotelina e outros (30)(31)(32) . A hipertrofia de VE e VD observada neste estudo poderia ter sido também causada pelo aumento da síntese e deposição de colágeno na matriz extracelular das células cardíacas, num processo inicial de fibrose ventricular, que pode ser oriundo, em parte, de um estímulo positivo direto dos EAA e/ou pela ação estimulatória da angiotensina-II no músculo cardíaco e no músculo liso vascular coronariano (16,32,33) .…”

Neurohumoral Control of Heart Rate

“…Indeed, estrogen replacement therapy reduces the incidence of coronary artery disease (Rowland & Fregly, 1992;Farhat et al, 1996). Corroborating these data, Moyses et al (2001) showed that estrogen treatment in ovariectomized female rats restored coronary vasodilation produced by serotonin in isolated hearts, and a bolus injection of 17ß-estradiol elicited a transient vasodilatory response in male and female normotensive (Santos et al, 2004) and spontaneously hypertensive rats . It has been already demonstrated that estrogen levels are also related with the development of cardiac arrhythmias.…”

Comparison of the effects of interferential current between male and female healthy adults

“…A review by Unruh [15] found that most studies described differences of pain sensation between genders, with females reporting higher intensity, duration and frequency of pain. This and other studies suggest relevant questions regarding the parameters of therapeutic modulation for analgesia between genders/sexes [15][16][17][18][19][20][21][22].…”