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

Abstract

Abstract Hydrogen sulfide (H2S) 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 H2S 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 H2S in the PVN, and that blood pressure, neuronal activation, oxidative stress, and inflammation of PVN were all substantially reduced. In addition, PVN endogenous H2S 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 H2S on hypertension. These results suggest that PVN endogenous H2S can ameliorate hypertension through Nrf2-mediated antioxidant and anti-inflammatory effects.