title: 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.affiliation: Wake Forest School of Medicine, Winston-Salem, North Carolina (H.J.C., N.O., H.H., A.M., D.M.H., W.C.L., C.P.C.), and the First Affiliated Hospital of Harbin Medical University, Harbin, China (T.L., H.J.C, W.L., C.P.C).
authors.forename: Tiankai
authors.initials: T
authors.lastname: Li
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, North Carolina (H.J.C., N.O., H.H., A.M., D.M.H., W.C.L., C.P.C.), and the First Affiliated Hospital of Harbin Medical University, Harbin, China (T.L., H.J.C, W.L., C.P.C).
authors.forename: Heng-Jie
authors.initials: HJ
authors.lastname: Cheng
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, North Carolina (H.J.C., N.O., H.H., A.M., D.M.H., W.C.L., C.P.C.), and the First Affiliated Hospital of Harbin Medical University, Harbin, China (T.L., H.J.C, W.L., C.P.C).
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ohte
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, North Carolina (H.J.C., N.O., H.H., A.M., D.M.H., W.C.L., C.P.C.), and the First Affiliated Hospital of Harbin Medical University, Harbin, China (T.L., H.J.C, W.L., C.P.C).
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, North Carolina (H.J.C., N.O., H.H., A.M., D.M.H., W.C.L., C.P.C.), and the First Affiliated Hospital of Harbin Medical University, Harbin, China (T.L., H.J.C, W.L., C.P.C).
authors.forename: Atsushi
authors.initials: A
authors.lastname: Morimoto
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, North Carolina (H.J.C., N.O., H.H., A.M., D.M.H., W.C.L., C.P.C.), and the First Affiliated Hospital of Harbin Medical University, Harbin, China (T.L., H.J.C, W.L., C.P.C).
authors.forename: David M
authors.initials: DM
authors.lastname: Herrington
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, North Carolina (H.J.C., N.O., H.H., A.M., D.M.H., W.C.L., C.P.C.), and the First Affiliated Hospital of Harbin Medical University, Harbin, China (T.L., H.J.C, W.L., C.P.C).
authors.forename: William C
authors.initials: WC
authors.lastname: Little
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, North Carolina (H.J.C., N.O., H.H., A.M., D.M.H., W.C.L., C.P.C.), and the First Affiliated Hospital of Harbin Medical University, Harbin, China (T.L., H.J.C, W.L., C.P.C) ccheng@wakehealth.edu liweimin_2009@163.com.
authors.forename: Weimin
authors.initials: W
authors.lastname: Li
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, North Carolina (H.J.C., N.O., H.H., A.M., D.M.H., W.C.L., C.P.C.), and the First Affiliated Hospital of Harbin Medical University, Harbin, China (T.L., H.J.C, W.L., C.P.C) ccheng@wakehealth.edu liweimin_2009@163.com.
authors.forename: Che Ping
authors.initials: CP
authors.lastname: Cheng
mesh_terms: D000818:Animals; D003971:Diastole / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology* / Q000627:therapeutic use; D010805:Physical Conditioning, Animal; D020127:Recovery of Function / Q000187:drug effects*; D012146:Rest / Q000502:physiology*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D020098:Natriuretic Peptide, C-Type