Abstract 18357: Hypertension in Mice Lacking 3-Mercaptopyruvate Sulfurtransferase
Background: Hydrogen sulfide (H2S) is synthesized by three distinct H2S synthase isoforms, including cystathionine gamma-lyase (CSE), cystathionine beta-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3MST). Although the regulatory roles of CSE and CBS in the cardiovascular system have been described, little is known about the role of 3MST. In this study, we investigated our hypothesis that 3MST regulates arterial blood pressure in mice.
Methods and Results: Experiments were performed in male 3MST gene-deficient (3MST-/-) mice and wild-type (WT) littermates. Blood pressure in those mice was measured under conscious conditions by two different analytical methods (i.e., the tail-cuff and telemetry methods). Cardiac output and peripheral vascular resistance were assessed by hemodynamic measurements in the ascending aorta using a Doppler-type ultrasonic flowmeter under inhalation anesthesia with isoflurane. We confirmed deletion of the 3MST mRNA and protein in the 3MST-/- genotype by real-time PCR and Western blot analysis, respectively. Both the tail-cuff and telemetric blood pressure measurements showed that arterial blood pressure was significantly higher in the 3MST-/- genotype as compared with the WT genotype. Cardiac output was comparable between the two genotypes, whereas peripheral vascular resistance was significantly increased in the 3MST-/- than in the WT genotype. There were no significant differences in the low to high frequency ratio of heart rate variability, a marker of sympathetic nerve activity, or in plasma angiotensin II or aldosterone levels, markers of activation of the renin-angiotensin-aldosterone system, in the two genotypes. On the other hand, plasma 8-isoprostane levels, a marker of oxidative stress, were significantly higher in the 3MST-/- genotype compared with the WT genotype, suggesting that increased oxidative stress is involved, at least in part, in blood pressure elevation in the 3MST-/- genotype.
Conclusions: These results provide the first evidence that disruption of the 3MST gene results in a rise in blood pressure in mice in vivo possibly through increased oxidative stress, demonstrating the novel blood pressure-lowering role of 3MST.
Author Disclosures: M. Tsutsui: None. Y. Totsuka: None. M. Sakanashi: None. T. Matsuzaki : None. K. Noguchi: None. J. Nakasone: None. Y. Kuniyoshi: None.
- © 2016 by American Heart Association, Inc.