by
Adrienne King;
David J. Polhemus;
Shashi Bhushan;
Hiroyuki Otsuka;
Kazuhisa Kondo;
Chad K. Nicholson;
Jessica M. Bradley;
Kazi N. Islam;
John Calvert;
Ya-Xiong Tao;
Tammy R. Dugas;
Eric E. Kelley;
John W. Elrod;
Paul L. Huang;
Rui Wang;
David J. Lefer
Previous studies have demonstrated that hydrogen sulfide (H 2 S) protects against multiple cardiovascular disease states in a similar manner as nitric oxide (NO). H 2 S therapy also has been shown to augment NO bioavailability and signaling. The purpose of this study was to investigate the impact of H 2 S deficiency on endothelial NO synthase (eNOS) function, NO production, and ischemia/reperfusion (I/R) injury. We found that mice lacking the H 2 S-producing enzyme cystathionine γ-lyase (CSE) exhibit elevated oxidative stress, dysfunctional eNOS, diminished NO levels, and exacerbated myocardial and hepatic I/R injury. In CSE KO mice, acute H 2 S therapy restored eNOS function and NO bioavailability and attenuated I/R injury. In addition, we found that H 2 S therapy fails to protect against I/R in eNOS phosphomutant mice (S1179A). Our results suggest that H 2 S-mediated cytoprotective signaling in the setting of I/R injury is dependent in large part on eNOS activation and NO generation.
by
Shashi Bhushan;
Kazuhisa Kondo;
David Polhemus;
Hiroyuki Otsuka;
Chad Nicholson;
Ya-Xiong Tao;
Hui Huang;
Vasiliki Georgiopoulou;
Toyoaki Murohara;
John Calvert;
Javed Butler;
David J. Lefer