Search Results (2)

To explore the mechanism of action of CBS-derived H₂S in inducing cerebral vasodilation and activating BK_Ca channels. Sprague–Dawley (SD) rat middle cerebral arteries (MCA) were isolated from rat brains, and a pressure myography system was used to measure the effects of different concentrations of L-cysteine (L-Cys, 1 × 10^−5.5 to 1 × 10^−3.5 mol/L), a substrate for cystathionine-β-synthase (CBS)—a hydrogen sulfide (H₂S)-producing enzyme. Additionally, the effects of pretreatment with the CBS inhibitor amino-oxoacetate (AOAA, 1 mmol/L), the vascular endothelial growth factor receptor 2 inhibitor semaxanib (SU5416, 10 μmol/L), and the large-conductance calcium-activated potassium (BK_Ca) channel blocker iberiotoxin (IBTX, 100 nmol/L) were investigated to determine their impacts on CBS-derived H₂S-induced vasodilation. Acute digestion of rat vascular smooth muscle cells (VSMCs) was performed, and whole-cell patch-clamp techniques were used to measure current changes in neurons or astrocytes (ASTs), as well as acutely digested VSMCs, in the presence of L-Cys, AOAA (1 mmol/L), SU5416 (10 μmol/L), and IBTX (100 nmol/L). Additionally, neurons or ASTs were co-cultured with VSMCs to determine CBS-derived H₂S levels. Neurons or ASTs co-incubated with blood vessels and then treated with L-Cys produced H₂S, which exhibited a concentration-dependent dilatory effect on middle cerebral artery occlusion (MCA) pre-contracted with 100 nmol/L U46619 (p < 0.01). However, the addition of AOAA significantly attenuated this dilatory effect (p < 0.01). SU5416 and IBTX significantly inhibited cerebral vascular dilation (p < 0.01). H₂S produced by adding L-Cys after co-incubation of neurons or ASTs with VSMCs significantly increased BK_Ca channel current (p < 0.01). However, this effect was significantly attenuated after adding AOAA (p < 0.01). SU5416 and IBTX significantly inhibited the activation of BK_Ca channels (p < 0.01). Wild-type rat neurons or astrocytes (ASTs) were co-cultured with CSE(Cystathionine γ-lyase)-knockout vascular smooth muscle cells (VSMCs-CSE KO); the addition of L-Cys significantly increased hydrogen sulfide (H₂S) levels in the co-culture system (p < 0.01), while the addition of AOAA reduced H₂S production (p < 0.01). However, the addition of SU5416 had no statistical significance. Neurogenic H₂S, the H₂S produced by neurons and ASTs, could induce cerebral vasodilation in rats via VEGFR₂(Vascular Endothelial Growth Factor Receptor 2)-mediated activation of BK_Ca channels in the smooth muscle cells. Full article

The reduced-gravity environment in space is known to cause an upward shift in body fluids and thus require cardiovascular adaptations in astronauts. In this study, we recorded in rats the neuronal activity in the subthalamic cerebrovasodilator area (SVA), a key area that controls cerebral blood flow (CBF), in response to partial gravity. “Partial gravity” is the term that defines the reduced-gravity levels between 1 g (the unit gravity acceleration on Earth) and 0 g (complete weightlessness in space). Neuronal activity was recorded telemetrically through chronically implanted microelectrodes in freely moving rats. Graded levels of partial gravity from 0.4 g to 0.01 g were generated by customized parabolic-flight maneuvers. Electrophysiological signals in each partial-gravity phase were compared to those of the preceding 1 g level-flight. As a result, SVA neuronal activity was significantly inhibited by the partial-gravity levels of 0.15 g and lower, but not by 0.2 g and higher. Gravity levels between 0.2–0.15 g could represent a critical threshold for the inhibition of neurons in the rat SVA. The lunar gravity (0.16 g) might thus trigger neurogenic mechanisms of CBF control. This is the first study to examine brain electrophysiology with partial gravity as an experimental parameter. Full article