Gender differences in the effects of streptozotocin-induced diabetes on parasympathetic vasodilatation in the rat submandibular gland

Abstract

Objectives-Submandibular vasodilatory responses are impaired in male streptozotocin-diabetic rats. However, the effects of diabetes on submandibular vascular reactivity in female rats have not been examined. The purpose of this study was to determine whether there are gender differences in the effects of diabetes on parasympathetic vasodilatation in the rat submandibular gland.Methods-Diabetes was induced using streptozotocin, and vascular responses (calculated as the % increase in submandibular vascular conductance) to parasympathetic stimulation (1-10 Hz) were measured using laser-Doppler flowmetry. To estimate the relative contributions of nitric oxide (NO), prostacyclin (PGI 2 ) and endothelium-derived hyperpolarizing factor (EDHF), vascular conductance was measured before and after inhibition of cyclooxygenase (COX) and NO synthase (NOS).Results-Frequency dependent increases in blood flow were observed in both male and female rats, but the contribution of EDHF was greater in females than in males. Further, PGI 2 appeared to play a role only in males. Vasodilatory responses were diminished in all diabetic animals, and when compared with their respective controls the degree of impairment was similar in males and females. However, in diabetic males inhibition of COX and NOS had little or no effect, whereas inhibition of NO, but not COX, resulted in a further significant decrease in vascular responses in diabetic females.Conclusions-Parasympathetic vasodilatation in the rat submandibular gland is diminished equally in diabetic males and females. However, in males diabetes predominantly impairs PGI 2 -and NO-dependent vasodilatation, whereas in females the contribution of EDHF-mediated pathways are affected and NO-dependent vasodilatation is preferentially maintained.

Impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated parotid artery of the alloxan-induced diabetic rabbit

“…Diabetes is probably the metabolic disease most frequently associated with salivary flow hypofunction. Decreased secretion of saliva in diabetes is induced not only by impairment of the structure (1) and functions (2) of salivary cells and the lowered susceptibility of muscarinic receptors (3), but also by changes in salivary gland blood flow (4, 5). The adverse effects of diabetes mellitus on vascular physiology have been well documented and endothelial dysfunction represents a key event in the development of microvascular and macrovascular complications (6).…”

“…The adverse effects of diabetes mellitus on vascular physiology have been well documented and endothelial dysfunction represents a key event in the development of microvascular and macrovascular complications (6). Bearing in mind that parasympathetic stimulation of salivary glands promotes salivation, to which the accompanying vasodilation contributes significantly, an important finding was that diabetes significantly impaired parasympathetically induced blood flow in vivo within the microvascular system of the rat submandibular gland (4, 5). However, there are no data reporting the effect of diabetes on the in vitro reactivity of salivary gland feeding arteries to the parasympathetic neurotransmitter acetylcholine (ACh); analysis of this macrovascular event could provide greater insight into the pathophysiological mechanisms of diabetic vascular injury.…”

17β-Estradiol Treatment Improves Acetylcholine-Induced Relaxation of Mesenteric Arteries in Ovariectomized UC Davis Type 2 Diabetes Mellitus Rats in Prediabetic State

“…The prevalence of CVD in premenopausal women is less than age-matched men, and female sex hormones, estrogen in particular, play a role in sex-specific cardiovascular protection in females (Barrett-Connor, 1994;Iorga et al, 2017). Several studies including ours suggest that diabetes affects male and female vascular beds differently (Witcher et al, 2010;Zhang et al, 2012;Lum-Naihe et al, 2017;Shaligram et al, 2020;Akther et al, 2021). Diabetes not only abrogates the female-specific cardiovascular protection, but also premenopausal women with diabetes experience higher CVD events than diabetic men (Peters et al, 2015;Castro, 2016), suggesting that hyperglycemia may overcome some of the beneficial effects of female sex hormones.…”

Salivary gland hypofunction in KK‐Ay type 2 diabetic mice

“…Reduced salivary gland function is also associated with metabolic diseases, such as diabetes mellitus. Some of the effects of diabetes on salivary glands include diabetes‐induced reductions in sympathetic activity to the salivary gland, a possible role for autonomic neuropathy in the abnormal response of the parotid gland to parasympathetic nerve stimulation in diabetic rats, and reduced parasympathetic vasodilatation in the submandibular gland (SMG) in diabetic rats, which may result in salivary dysfunction . Furthermore, diabetes increases the expression of sodium–glucose cotransporter 1 (SGLT1), which works as a water transporter, in salivary duct cells, which may be one of the causes of diabetes‐induced salivary dysfunction .…”