Hypothalamic paraventricular nucleus hydrogen sulfide exerts antihypertensive effects in spontaneously hypertensive rats by attenuating oxidative stress via the Nrf2 pathway

Abstract Hydrogen sulfide (H 2 S) is widely distributed throughout the nervous system with various antioxidant and anti-inflammatory properties. Increased reactive oxygen species and inflammation in the hypothalamic paraventricular nucleus (PVN) are involved in the pathophysiology of hypertension. But it is unclear how H 2 S in PVN affects hypertension. Our study used spontaneously hypertensive rats (SHR) and control Wistar Kyoto (WKY) rats, microinjected with AAV-CBS (cystathionine beta-synthase overexpression) or AAV-ZsGreeen in the bilateral PVN; or simultaneously injected with virus-carrying nuclear factor erythroid 2-related factor 2 (Nrf2)-shRNA. We found that AAV-CBS increased H 2 S in the PVN, and that blood pressure, neuronal activation, oxidative stress, and inflammation of PVN were all substantially reduced. In addition, PVN endogenous H 2 S activated Nrf2 and corrected the PVN's unbalanced of excitatory and inhibitory neurotransmitters. However, Nrf2 knockdown in the PVN was similarly observed to abolish the beneficial effect of H 2 S on hypertension. These results suggest that PVN endogenous H 2 S can ameliorate hypertension through Nrf2-mediated antioxidant and anti-inflammatory effects.