The role of hydrogen sulfide generation in the pathogenesis of hypertension in rats induced by inhibition of nitric oxide synthase

OBJECTIVEThe present study intended to investigate whether the impaired H2S synthase/H2S pathway is associated with hypertension. METHODSHypertension in Wistar rats was induced by the oral administration of the l-arginine analog, N-nitro-l-arginine methyl ester (l-NAME) in their drinking water for a period of 6 weeks. The control rats were given plain tap water only. Sodium hydrosulfide (NaHS) was given by intraperitoneal injection to both the control group and the l-NAME-treated group. The systolic BP (blood pressure) was measured by a tail-cuff method using a pulse transducer. Plasma hydrogen sulfide (H2S), and H2S generation by thoracic aorta and superior mesenteric artery, were determined. In addition, the activity of cystathionine-γ-lyase (CSE) in thoracic aorta and superior mesenteric artery, most responsible for H2S production, was also measured. Competitive reverse transcriptase–polymerase chain reaction (RT-PCR) was used to determine CSE mRNA in thoracic aorta. RESULTSl-NAME caused a time-dependent elevation of systolic BP. The heart-to-body weight ratio of l-NAME-treated rats was 27% higher than that of controls. The systolic BP in the NaHS-treated l-NAME group was significantly decreased, by 19% (P < 0.01), in comparison with the l-NAME group. The heart-to-body weight ratio decreased significantly by 12%. l-NAME inhibited CSE gene expression significantly. The inhibition of H2S generation and CSE activity by l-NAME was greatly attenuated in the NaHS-treated l-NAME group. However, there was no significant difference in nitric oxide (NO) generation between the l-NAME group and the NaHS-treated l-NAME group. CONCLUSIONIn summary, dysfunction of the vascular H2S synthase/H2S pathway was found in l-NAME-induced hypertensive rats. Exogenous H2S effectively prevented the development of hypertension induced by l-NAME. These findings suggest that the H2S synthase/H2S pathway participates in hypertension.