Changes and significance of hydrogen sulfide/cystathionine gamma-lyase system in hypertension: an experimental study with rats

Abstract

To explore the significance of hydrogen sulfide/cystathionine gamma-lyase (H(2)S/CSE) system in the development of hypertension and the effects of H(2)S/CSE system on the modulation of aortic remodeling process of hypertension. Eight 4-week-old male WKY rats were used as WKY control group, and another sixteen SHR rats at the age of 4 weeks were randomly divided into SHR control group (n = 8) and SHR + NaHS (H(2)S donor) group (n = 8). The rats of SHR control and WKY control were injected with normal saline and the rats of the SHR + NaHS group were injected with NaHS each day. Five weeks later, the blood pressure and the left-to-whole heart weight ratio were determined. The transcriptional level of CSE in aorta and the H(2)S level in plasma were detected. The morphometric parameters of the thoracic aorta including the outer radius, medium area and ratio of wall thickness to lumen radius were detected too. At the age of 9 weeks the systolic blood pressure and the left-to-whole heart weight ratio of the SHR control rats were both higher than those of the WKY control rats [(184 +/- 12) mm Hg vs (108 +/- 23) mm Hg, 1 mm Hg = 0.133 kPa, and (0.853 +/- 0.021) vs (0.826 +/- 0.024)]. The transcriptional level of CSE in aorta and the H(2)S level in serum of the rats in the SHR control group were both lower than those of the rats in the WKY control group (9.3 +/- 0.7) x 10(-8) fmol vs (16.1 +/- 1.0) x 10(-8) fmol, and (20 +/- 9) micro mol/L vs (48 +/- 13) micro mol/L, while the morphometric parameters of the thoracic aorta including the outer radius, the medium area and ratio of lumen radius and wall thickness of the SHR control rats were all higher compared with those of the WKY control rats [outer radius: (1999 +/- 45) micro m vs (1790 +/- 96) micro m], medium area: (0.60 +/- 0.06) mm(2) vs (0.48 +/- 0.03) mm(2), and ratio of wall thickness to lumen radius: (0.066 +/- 0.006) vs (0.060 +/- 0.004). The exogenous administration of NaHS made the systolic blood pressure of rats in the SHR + NaHS group much lower than that of the rats in SHR control group [(158 +/- 13) mm Hg vs (184 +/- 12) mm Hg], however, the transcriptional level of CSE in aorta and the H(2)S level in serum of the rats in SHR + NaHS group were much higher than those of the rats in SHR control group [(12.4 +/- 1.0) x 10(-8) fmol vs (9.3 +/- 0.7) x 10(-8) fmol] vs [(96 +/- 32) micro mol/L vs (20 +/- 9) micro mol/L]. The morphometric parameters of SHR + NaHS group were lower than those of the SHR control group. Down regulation of H(2)S/CSE system is a major factor in the development of spontaneous hypertension and the accompanying structural remodeling of aorta. Exogenous administration of H(2)S may attenuate the process of hypertension.