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.
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 tapwater 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 hypertensiverats. Exogenous H2S effectively prevented the development of hypertension induced by l-NAME. These findings suggest that the H2S synthase/H2S pathway participates in hypertension.
Authors: Asif K Mustafa; Gautam Sikka; Sadia K Gazi; Jochen Steppan; Sung M Jung; Anil K Bhunia; Viachaslau M Barodka; Farah K Gazi; Roxanne K Barrow; Rui Wang; L Mario Amzel; Dan E Berkowitz; Solomon H Snyder Journal: Circ Res Date: 2011-10-06 Impact factor: 17.367
Authors: P M Snijder; A R Frenay; R A de Boer; A Pasch; J L Hillebrands; H G D Leuvenink; H van Goor Journal: Br J Pharmacol Date: 2015-03 Impact factor: 8.739