Cardiovascular disease (CVD) is a major source of morbidity and mortality in the Western World. Premenopausal and estrogen-treated postmenopausal women have a lower incidence of CVD. It has been suggested that circulating endogenous estrogens are probably responsible for this protection. This study investigated the hypothesis that the reduction of endothelial permeability is responsible for cardioprotective effects of estrogen in hypertensive animals. Fourty-four rats were ovariectomized and divided into five groups: groups 1, 2 and 4 received DOCA-salt and groups 3 and 5 received normal saline (N/S) injection for four weeks. Then, in groups 4 and 5 the blood pressure was measured. Group 1 received estradiol valerate and in groups 2 and 3 continued with DOCA-salt and N/S injection for six weeks, respectively. Endothelial permeability was measured by Evans Blue extraction method. There was no significant difference in endothelial permeability in coronary circulation in estrogen-treated group and controls (12.97±2.32 vs. 9.96±1.01, respectively). Also, aortic endothelial permeability in DOCA-salt hypertensive rats did not change significantly after estrogen treatment (28.34±3.65 vs. 41.60±5.98). This study showed that the cardioprotective effects of estrogen in DOCA-salt hypertensive animals are not mediated by a reduction of endothelial permeability.
We evaluated the effects of exercise on the vascular constrictor responses to α-adrenergic stimulation in the db/db mice. Twenty male db/db and their age-matched wild-type (WT) mice were exercised (1 hour/day, five days a week). Mice were anesthetized 7 weeks later, thoracic aortae were mounted in wire myograph and constrictor responses to phenylephrine (PE, 1 nM-10 μM) were obtained. Citrate synthase activity measured in the thigh adductor muscle was significantly increased in db/db mice that were exercise trained. Maximal force generated by PE was markedly greater in db/db aortae and exercise did not attenuate this augmented contractile response. Vessels were incubated with inhibitors of nitric oxide synthase (L-NAME, 200 μM), endothelin receptors (bosentan, 10 μM), protein kinase C (PKC) (calphostin C, 5 μM), cyclooxygenase (indomethacin, 10 μM) or Rho-kinase (Y-27632, 0.1 μM). Only calphostin-C normalized the augmented PE-induced constriction in db/db and db/db- exercised mice to that observed in WT (p<0.05). Cumulative additions of indolactam, a PKC activator, induced significantly greater constrictor responses in aortic rings of db/db mice compared to WT and exercise did not affect this response. Our data suggest that the augmented vasoconstriction observed in the aorta of db/db mice is likely due to increased PKC activity and that exercise do not ameliorate this increased PKC-mediated vasoconstriction., M. Khazaei, F. Moien-Afshari, T. J. Kieffer, I. Laher., and Obsahuje bibliografii a bibliiografické odkazy