C-Type Natriuretic Peptide Improves Left Ventricular Functional Performance at Rest and Restores Normal Exercise Responses after Heart Failure
| Autor: | Atsushi Morimoto, Nobuyuki Ohte, Hiroshi Hasegawa, Tiankai Li, David M. Herrington, William C. Little, Heng-Jie Cheng, Wei-Min Li, Che Ping Cheng |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Lusitropy medicine.drug_class Rest Diastole Hemodynamics Vasodilation 030204 cardiovascular system & hematology Cardiovascular Contractility Ventricular Dysfunction Left 03 medical and health sciences Dogs 0302 clinical medicine Physical Conditioning Animal Internal medicine medicine Natriuretic peptide Animals Humans Heart Failure Pharmacology Dose-Response Relationship Drug business.industry Natriuretic Peptide C-Type Recovery of Function medicine.disease 030104 developmental biology Endocrinology Heart failure Ventricular pressure Molecular Medicine Female business |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 357:545-553 |
| ISSN: | 1521-0103 |
| DOI: | 10.1124/jpet.115.231696 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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