Epidemiological data suggest that hyperglycemia abrogates the gender-based cardiovascular protection possibly associated with estrogens. This study was designed to investigate 1) whether rabbit aortic rings show gender differences in the development of abnormal endothelium-dependent vasodilation (EDV) under acute hyperglycemic conditions, 2) the potential role of PKC isoforms and superoxide (O2−) in acute hyperglycemia-induced vascular dysfunction, and 3) the effect of acute estrogen administration on hyperglycemia-induced endothelial dysfunction in male and female rabbits. EDV to ACh was determined before and after 3 h of treatment with high glucose (HG) in phenylephrine-precontracted aortic rings from male and female New Zealand White rabbits. Similar experiments were conducted in the presence of inhibitors of PKC-α, PKC-β, and PKC-δ or an O2− scavenger. The effect of acute estrogen administration was evaluated in the presence and absence of HG. Finally, mRNA expression of PKC isoforms was measured by real-time PCR. We found that 1) 3 h of incubation with HG impairs EDV to a greater extent in female than male aorta, 2) inhibition of PKC-β or O2− prevents HG-induced impairment of EDV in female aorta, 3) acute 17β-estradiol aggravates HG-induced endothelial dysfunction in female, but not male, aorta, and 4) PKC-α and PKC-β expression are significantly higher in female than male aorta. This study reveals the predisposition of female rabbit aorta to vascular injury under hyperglycemic conditions, possibly via activation of PKC-β and O2− production. Furthermore, it suggests that, under hyperglycemic conditions, acute estrogen treatment is detrimental to endothelial function in female rabbits.
Undercarboxylated osteocalcin has no adverse effect on endothelial function in rabbit aorta or human vascular cells
