Cystathionine-β-Synthase Gene Transfer Into Rostral Ventrolateral Medulla Exacerbates Hypertension via Nitric Oxide in Spontaneously Hypertensive Rats Xiao-Cui Duan,1,2 Shang-Yu Liu,1 Rong Guo,3 Lin Xiao,1 Hong-Mei Xue,1 Qi Guo,1 Sheng Jin,1 and Yu-Ming Wu1

Hydrogen sulfide (H2S) is an endothelium-derived hyperpolarizing factor that enhances the relaxation of the peripheral vasculature,1–3 recent studies4–6 have also reported its physiological functions in the central nervous system. In mammalian tissues, H2S is produced through degradation of l-cysteine mainly by 2 main enzymes: cystathionineβ-synthase (CBS) and cystathionine-γ-lyase. CBS is primarily found in the brain, whereas cystathionine-γ-lyase is mainly expressed in the peripheral tissues.7 The role of H2S in cardiovascular regulation has been investigated in specific areas of the central nervous system, including the nucleus tractus solitarii,8 paraventricular nucleus of the hypothalamus,5 and rostral ventrolateral medulla (RVLM).6,9 It is well known that the RVLM is an important central site responsible for maintaining baseline sympathetic vasomotor tone and arterial blood pressure (ABP);10,11 abnormalities in this brain region may be directly relevant to the pathophysiology of heart failure12,13 and hypertension.14,15 Although the precise function of H2S in cardiovascular regulation in the RVLM remains unclear, its role is very interesting due to the importance of the RVLM in the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). Previous studies have shown that the inhibitory system (nitric oxide, NO) in the RVLM is diminished in SHR.14,15 Moreover, accumulating evidence suggests that crosstalk occurs between the H2S and NO signaling pathways, which could induce synergistic16,17 or negatively related regulatory effects.18–20 In this study, the expression of the CBS protein and H2S production were decreased in the RVLM of SHR compared to the normotensive WistarKyoto (WKY) rats. Therefore, we hypothesize that the decrease in CBS in the RVLM is involved in the disorder of the NO/nitric oxide synthase (NOS) pathway in SHR and affects blood pressure (BP). Therefore, we tested this hypothesis by overexpressing CBS via recombinant adenovirus vectors encoding CBS gene transfected into the RVLM in vivo. Cystathionine-β-Synthase Gene Transfer Into Rostral Ventrolateral Medulla Exacerbates Hypertension via Nitric Oxide in Spontaneously Hypertensive Rats