Effect of type 1 diabetes on the production and vasoactivity of hydrogen sulfide in rat middle cerebral arteries

Abstract

Hydrogen sulfide (H2S) is produced endogenously in vascular tissue and has both vasoregulation and antioxidant effects. This study examines the effect of diabetes-induced oxidative stress on H2S production and function in rat middle cerebral arteries. Diabetes was induced in rats with streptozotocin (50 mg/kg, i.v.). Middle cerebral artery function was examined using a small vessel myograph and superoxide anion generation measured using nicotinamide adenine dinucleotide phosphate (NADPH)-dependent lucigenin-enhanced chemiluminescence. Cystathionine-γ-lyase (CSE) mRNA expression was measured via RT-PCR. Diabetic rats had elevated blood glucose and significantly reduced cerebral artery endothelial function. Maximum vasorelaxation to the H2S donor NaHS was unaffected in diabetic cerebral arteries and was elicited via a combination of K+, Cl−, and Ca2+ channel modulation, although the contribution of Cl− channels was significantly less in the diabetic cerebral arteries. Vasorelaxation to the H2S precursor l-cysteine and CSE mRNA were significantly increased in diabetic cerebral arteries. Cerebral artery superoxide production was significantly increased in diabetes, but this increase was attenuated ex vivo by incubation with the H2S donor NaHS. These data confirm that cerebral artery endothelial dysfunction and oxidative stress occurs in diabetes. Endogenous H2S production and activity is upregulated in cerebral arteries in this model of diabetes. Vasorelaxation responses to exogenous H2S are preserved and exogenous H2S attenuates the enhanced cerebral artery generated superoxide observed in the diabetic group. These data suggest that upregulation of endogenous H2S in diabetes may play an antioxidant and vasoprotective role.

Hydrogen sulfide treatment reduces blood pressure and oxidative stress in angiotensin II-induced hypertensive mice

“…Previous work has shown a similar effect in an atherosclerosis model 45 suggesting a role for H 2 S as a vascular antioxidant. In addition, H 2 S has been reported to act as a scavenger for a variety of ROS, including superoxide, 16,46,47 hydrogen peroxide, 43 peroxynitrite 12,13 and hypochloride. 15 Thus, H 2 S may both inhibit vascular ROS production and act as a scavenger of ROS, increasing its anti-oxidant potential.…”

Role of Endothelial Dysfunction in Cardiovascular Diseases: The Link Between Inflammation and Hydrogen Sulfide

“…By contrast, the protein and mRNA expression of CBS are specifically decreased in the kidney, while CSE expression remains unchanged in obese diabetic mice (Liu et al, 2018). Interestingly, CSE expression is upregulated in cerebral microvessels of type I diabetic rats (Streeter et al, 2013). Although the data are conflicting, they raise the possibility that H 2 S may be a double-edged sword under diabetic pathophysiology.…”

The role of H2S bioavailability in endothelial dysfunction

“…There are also no changes in the expression of CSE, CBS or MST in endothelial cells exposed to elevated extracellular glucose, or in the thoracic aorta of streptozotocin-diabetic rats [50, 55]. In fact, CSE expression in cerebral microvessels was increased in type I diabetes [56]. …”