In heart failure (HF), the impaired left ventricular (LV) arterial coupling and diastolic dysfunction present at rest are exacerbated during exercise. C-type natriuretic peptide (CNP) is elevated in HF; however, its functional effects are unclear. We tested the hypotheses that CNP with vasodilating, natriuretic, and positive inotropic and lusitropic actions may prevent this abnormal exercise response after HF. We determined the effects of CNP (2 μg/kg plus 0.4 μg/kg per minute, i.v., 20 minutes) on plasma levels of cGMP before and after HF and assessed LV dynamics during exercise in 10 chronically instrumented dogs with pacing-induced HF. Compared with the levels before HF, CNP infusion caused significantly greater increases in cGMP levels after HF. After HF, at rest, CNP administration significantly reduced LV end-systolic pressure (PES), arterial elastance (EA), and end-diastolic pressure. The peak mitral flow (dV/dtmax) was also increased owing to decreased minimum LVP (LVPmin) and the time constant of LV relaxation (τ) (P < 0.05). In addition, LV contractility (EES) was increased. The LV-arterial coupling (EES/EA) was improved. The beneficial effects persisted during exercise. Compared with exercise in HF preparation, treatment with CNP caused significantly less important increases in PES but significantly decreased τ (34.2 vs. 42.6 ms) and minimum left ventricular pressure with further augmented dV/dtmax. Both EES, EES/EA (0.87 vs. 0.32) were increased. LV mechanical efficiency improved from 0.38 to 0.57 (P < 0.05). After HF, exogenous CNP produces arterial vasodilatation and augments LV contraction, relaxation, diastolic filling, and LV arterial coupling, thus improving LV performance at rest and restoring normal exercise responses after HF.
- Received December 22, 2015.
- Accepted March 28, 2016.
This study was supported, in part, by grants from the National Institutes of Health (NIH) (Grant AG049770 to H.J.C.); the NIH (Grant HL074318), American Heart Association Grant-in-Aid (Grant 11GRNT7240020) (to C.P.C.); and the National Natural Science Foundation of China (Grant 81270252) (to W.M.L.).
This work was previously presented as an abstract at the American Heart Association Meeting in 2014 and published as Che Ping Cheng, Hiroshi Hasegawa; Atsushi Morimoto; Heng-Jie Cheng; William C. Little. (2014) C-type natriuretic peptide improves left ventricular systolic and diastolic functional performance at rest and during exercise after heart failure. Circulation 130:A12583.
- Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics