Abstract 14266: Guanosine 3',5'-Cyclic Monophosphate Levels Are Increased in Plasma but Reduced in Left Ventricular Myocardium of Dogs with Chronic Hear Failure
Background: Dysfunctional cyclic guanosine 3′,5′-monophosphate (cGMP) signaling has been implicated in numerous cardiovascular diseases, including heart failure (HF). Reduced cGMP level has been reported in myocardium of isoproterenol-induced cardiomyopathic heart but very limited information is available on cGMP levels in plasma and myocardium of large animals with experimentally-induced heart failure (HF). We previously reported significantly increased plasma and left ventricular (LV) tissue levels of natriuretic peptides, nt-proBNP and proANP in dogs with coronary microembolization-induced HF. Though these natriuretic peptides synthesize cGMP via activating particulate guanulate cyclase, the fate of cGMP level in plasma and LV tissue of dogs with microembolization-induced HF dogs is not known. This study examined levels of cGMP in plasma and LV tissue of dogs with microembolization-induced chronic HF.
Methods: Plasma and LV tissue were obtained from 6 HF dogs (LV EF-ejection fraction, <30%) and 6 normal (NL) dogs. cGMP was extracted from frozen plasma or LV tissue powder and was acetylated and assayed for cGMP content by specific enzyme immunoassay (EIA) kit and expressed in pmol/ml for plasma and pmol/mg protein in LV samples.
Results: cGMP level was significantly increased in plasma of dogs with HF compared to NL dogs (31.3 ± 1.3 vs. 6.3 ± 0.4 pmol/ml, p<0.05). In contrast, cGMP levels were significantly decreased in LV tissue of HF dogs compared to NL (0.46 ± 0.06 vs. 1.01 ± 0.21 pmol/mg, p<0.05).
Conclusions: In dogs with HF, levels of cGMP are increased in plasma but decreased in LV tissue. Reduced cGMP level in LV myocardium of dogs with HF is indicative of impaired cGMP signaling. These findings are consistent with observations of increased cGMP-phosphodiesterase-5 (PDE5) activity and expression in LV myocardium of failing hearts and suggest possible therapy for HF based on guanylate cyclase activation and/or inhibition of cGMP specific phosphodiesterses.
- © 2012 by American Heart Association, Inc.