Objective: The present study intended to investigate whether the impaired H2S synthase/H2S pathway is associated with hypertension.
Methods: Hypertension in Wistar rats was induced by the oral administration of the l-arginine analog, NG-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-gamma-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.
Results: l-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.
Conclusion: In 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.