C-Type Natriuretic Peptide Improves Left Ventricular Functional Performance at Rest and Restores Normal Exercise Responses after Heart Failure

Abstract

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 mg/kg plus 0.4 mg/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 (P ES ), arterial elastance (E A ), and end-diastolic pressure. The peak mitral flow (dV/dt max ) was also increased owing to decreased minimum LVP (LVP min ) and the time constant of LV relaxation (t) (P , 0.05). In addition, LV contractility (E ES ) was increased. The LV-arterial coupling (E ES /E A ) was improved. The beneficial effects persisted during exercise. Compared with exercise in HF preparation, treatment with CNP caused significantly less important increases in P ES but significantly decreased t (34.2 vs. 42.6 ms) and minimum left ventricular pressure with further augmented dV/dt max . Both E ES , E ES /E A (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.

C‐type natriuretic peptide induces inotropic and lusitropic effects in human 3D‐engineered cardiac tissue: Implications for the regulation of cardiac function in humans

“…In a mouse model of cardiac hypertrophy and remodelling induced by angiotensin II, CNP infusion also increased fractional shortening and decreased LVED dimension compared to the angiotensin II vehicle group, but no changes were observed with CNP when comparing with vehicle in the saline groups (Izumiya et al., 2012 ). In pacing‐induced HF in dogs, CNP augmented LV contraction, relaxation, diastolic filling and LV arterial coupling (Li et al., 2016 ). Taken collectively, observations in vivo suggest that CNP elicits both inotropic and lusitropic responses in preclinical models of HF.…”

Natriuretic Peptide Receptor B modulates the proliferation of the cardiac cells expressing the Stem Cell Antigen-1

“…Furthermore, CNP treatment reduces fibroblast collagen production and stimulates osteoblast and endothelial cell differentiation 37 38 . In vivo , CNP has been shown to be cardioprotective by improving left ventricle capacities after heart failure in dogs, by preventing cardiomyocyte hypertrophy in infarcted mouse hearts and by increasing cardiomyocyte relaxation and inotropic response in failing rat hearts 34 39 40 41 . Here in this report we showed that CNP is able to stimulate the proliferation of the cardiac Sca-1 + cells.…”

C-Type Natriuretic Peptide Ameliorates Lipopolysaccharide-Induced Cardiac Dysfunction in Rats with Pulmonary Arterial Hypertension

“…Rats in groups P1 and P2, C1, and C2 then received a normal saline infusion and the rats in group P3 and C3 were treated with CNP (CNP-53, The Peptide Institute, Osaka, Japan). CNP was given with a 2 μ g/kg loading dose plus a 0.4 μ g/kg/min infusion for 20 minutes [9]. Data were then recorded after 1 hour at T2.…”