Gender differences in mesenteric endothelial function of streptozotocin‐induced diabetic rats: Role of endothelium‐derived relaxing factors

Gender differences in mesenteric endothelial function were studied in male and female streptozotocin (60 mg/kg, iv)‐induced diabetic rats. Endothelium‐dependent vasodilation (EDV) to acetylcholine (ACh, 10 −8 to 10 −5 M) in mesenteric arteries precontracted with phenylephrine (2 μM) was measured before and after pretreatment with indomethacin (indo, 10 μM), a cyclooxygenase inhibitor, L‐NAME (200 μM), a nitric oxide (NO) synthase inhibitor, or barium chloride (100 μM), a K ir channel blocker, and ouabain (10 μM), a Na + ‐K + ‐ATPase inhibitor. Significant impairment of EDV was observed only in diabetic females. Indo decreased the sensitivity to ACh only in control males. Addition of L‐NAME reduced indo‐resistant vasodilation in females, but its effect was much greater in diabetic females. In control males, however, L‐NAME substantially blocked the remaining relaxation, and this effect was attenuated in diabetic males. Finally, the remaining indo‐ and L‐NAME‐resistant vasodilation was abolished by the combination of barium and ouabain in all groups. These data suggest that the predominant mediator in mesenteric vasodilation in females is endothelium‐derived hyperpolarizing factors (EDHF), whereas in males it is NO. Furthermore, there was a shift in the contributions of EDHF to NO in females and NO to EDHF in males following the induction of diabetes (Supported by NIDCR).