Effect of Gender and Diabetes on Submandibular Gland Blood Flow

INTRODUCTION: Following the onset of diabetes more women develop diabetic vascular complications when compared with men, and women are at a greater disadvantage than men once complications do develop. Endothelial dysfunction plays a key role in the development of diabetic vascular disease, in part through the impairment of nitric oxide (NO), prostacyclin (PGI2) and endothelium-derived hyperpolarizing factor (EDHF) release. OBJECTIVES: The purpose of this study was to determine the influence gender and diabetes on parasympathetic vasodilatation in the rat submandibular gland (SMG). METHODS: Male and female rats (n=49) were in these studies. Four to 5 weeks after the induction of diabetes (streptozotocin, 55 mg/kg), responses to parasympathetic stimulation (1-10 Hz) were measured using laser-Doppler flowmetry before and after inhibition of cyclooxygenase (indomethacin, 5 mg/kg i.p.) and NO synthase (L-NAME, continuous infusion 3 mg/min/kg, i.v.). RESULTS: In non-diabetic rats, parasympathetic stimulation resulted in increases in glandular perfusion (% increase above resting perfusion). No differences were observed between males and females. Diabetes resulted in a 40% decrease in stimulated blood flow (p<0.001) in both males and females. When eNOS and cyclooxygenase activities were blocked distinct gender differences were observed. In non-diabetic males, indomethacin and L-NAME sequentially reduced blood flow responses to parasympathetic stimulation, whereas inhibition of eNOS and cyclooxygenase had no effect in diabetic males. In contrast, indomethacin and L-NAME had minimal effects in non-diabetic females. In diabetic females, indomethacin again had no apparent effect but there was a significant reduction in blood flow response in the presence of L-NAME. CONCLUSIONS: We conclude that parasympathetic vasodilatation in the rat SMG is equally affected by diabetes in both male and female rats. However, in male rats diabetes predominantly affects PGI2- and NO-dependent vasodilatation, whereas in females EDHF release is diminished and NO-dependent vasodilatation is maintained. Supported by a grant DE016586 (NIDCR).