Results of Significance
It is now recognized that there are differences between males and females in the incidence and manifestation of vascular diseases, of which endothelial dysfunction is the underlying cause. Endothelial dysfunction is characterized by an imbalance between the release of endothelium-derived relaxing (EDRF) and contracting (EDCF) factors. It is precipitated by aging, western diet, obesity, diabetes and hypertension and thus becomes an increasing problem in societies like Hong Kong, facing the aging of the population combined with increasing access to western food.

The significance of EDCF in human vasculature is illustrated by the observations that inhibitors of its production (cyclooxygenase inhibitors) as well as those of its action (TP receptor blockers) restore a near normal endothelial function in hypertensive subjects. Therefore, the present study investigated whether or not female sex hormone has an influence on the production and/or the action of endothelium-derived contracting factors in hypertension.

Female Sprague Dawley rats (12 week old)
were divided into 3 groups: ovariectomized with 17ß-estradiol supplement (OVX-E group), ovariectomized with olive oil (vehicle for 17ß-estradiol) supplement (OVX-V group)and sham-operated with olive oil supplement (Sham group). When they were 18 week old, hypertension was induced in them by daily administration with the nitric oxide synthase inhibitor, L-NAME (60 mg/kg, by gavage) for 6 weeks, together with supplementation with 17ß-estradiol or its vehicle in the respective

group. For comparison, Male Sprague Dawley rats (18 week old) were also treated with L-NAME (60 mg/kg, by gavage) for 6 weeks. At the end of the pharmacological treatments, blood pressure was measured in these rats. Aorta was then isolated from these rats for the functional study and biochemical assay to examine endothelial function.

While chronic L-NAME treatment caused male rats to develop hypertension and their aorta to release EDCF, female rats of the same age were resistant to these effects of chronic L-NAME treatment. Such resistance was also observed in female rats with ovariectomy, and those with 17ß-estradiol supplement, suggesting that 17ß-estradiol may not be responsible for this gender difference. In male rat aorta, the occurrence of EDCF following chronic L-NAME treatment was associated with increased protein expressions of cyclooxygenase-1 and cyclooxygenase-2, the latter of which appeared to be responsible for the production of EDCF.

In summary, the present findings suggest that male rats are more prone to the development of hypertension than females at pre- or post-menopausal states. This increased risk may be associated with more severe endothelial dysfunction, with the occurrence of EDCF.