Regulation of Cerebral Blood Flow by Hydrogen Sulfide

H2S is formed from L‐Cysteine by cystathionine‐β‐synthase (CBS) and cystathionine‐γ‐lyase (CSE) and has been implicated in the regulation of neuronal function. Though, CBS is highly expressed in the brain, contribution of H2S to the regulation of cerebral blood flow (CBF) is not well understood. We examined the effects of H2S on CBF in anesthetized rats treated with H2S donor NaHS; precursor L‐Cysteine (50; 20 mg/kg) alone or following inhibition of CBS/CSE with Propargylyglycine (PPG; 75 mg/kg). Changes in CBF were determined by Laser Doppler Scanner (Moor LDI 5152). NaHS or L‐Cysteine increased basal CBF by 19 or 10%, while PPG reduced CBF by 33% (p<0.05). L‐Cysteine had no effect on PPG‐induced reduction of CBF but NaHS elicited a short‐lived reversal (13% at 30 min) that reverted to PPG level 60 min later. H2S‐induced regulation of CBF was influenced by age; L‐Cysteine increased CBF in the young (6 months) (17%) compared to sustained reduction (18%) in the adult (18 months). NaHS elicited a transient (5–15 min) increase in CBF in the young (22%) but produced a sustained reduction in the adult, reducing CBF to 49%. This study shows that the donor, precursor, and inhibitor of H2S synthase modulate CBF with differential effects in the adult versus young rats. Both H2S donor and precursor reduced adult CBF with the reduction being more pronounced by the donor. The differential effects could be due to age‐related loss of CBS/CSE. Thus, H2S synthetic pathway could play a significant role in neuropathology and serve as a therapeutic target for neurological diseases.