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 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.

• Authors: Tiankai Li, Heng-Jie Cheng, Nobuyuki Ohte, Hiroshi Hasegawa, Atsushi Morimoto, David M Herrington, William C Little, Weimin Li, Che Ping Cheng
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 357 Issue 3 Pg. 545-53 (06 2016) ISSN: 1521-0103 [Electronic] United States
• PMID: 27026682 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Chemical References

• Natriuretic Peptide, C-Type

Topics

• Animals
• Diastole (drug effects)
• Dogs
• Dose-Response Relationship, Drug
• Female
• Heart Failure (physiopathology)
• Hemodynamics (drug effects)
• Humans
• Male
• Natriuretic Peptide, C-Type (pharmacology, therapeutic use)
• Physical Conditioning, Animal
• Recovery of Function (drug effects)
• Rest (physiology)
• Ventricular Dysfunction, Left (drug therapy, physiopathology)