Abstract P366: Natriuretic Peptides Potentiate Cardiac Hypertrophic Response To Norepinephrine In Rats

Abstract

Background: The natriuretic peptide (NP) family consisting of ANP, BNP, and CNP is assumed to exert protective actions for the heart, alleviating hypertrophy and/or fibrosis of the myocardium. Excessive activation of the sympathetic nervous system is involved in cardiovascular damage including cardiac hypertrophy. In contrast to the previous notion, we show in the present study that both atrial and C-type natriuretic peptides (ANP and CNP) potentiate cardiac hypertrophic response to norepinephrine (NE) in rats. Methods and Materials: Nine-week-old male Wistar rats were continuously infused with subcutaneous 30 μg/h NE without or with persistent intravenous administration of either 1.0 μg/h ANP or CNP for 14 days. The NE plus ANP groups were treated orally without or with either 5 mg/day prazosin or 50 mg/day atenolol during this study period. Sample sizes are follows: control, NE, NE plus ANP, n=8 to 9; CNP, NE plus CNP, prazosin, atenolol, n=6 to 7. Blood pressure (BP) was recorded via a catheter placed in the abdominal aorta under an unrestrained condition by a radiotelemetry system. Cardiac hypertrophic response to NE was evaluated by heart weight to body weight (HW/BW) ratio. Left ventricular (LV) tissues were also examined microscopically to measure individual myocyte size and collagen deposition. Results: Mean BP levels at the light and dark cycles rose by 20 and 17 mmHg, respectively, following NE infusion for 14 days, with slight increases in HW/BW ratio (+7.6%) and ventricular myocyte size (+20%), compared to control (P>0.05). Infusions of ANP and CNP had no significant effects on mean BP in NE-infused rats, while two natriuretic peptides potentiated cardiac hypertrophic response to NE at day 14 (HW/BW and myocyte size: NE plus ANP, +37% and +64%; NE plus CNP, +47% and +56%, respectively; P<0.01 for all). No differences were noted in collagen volume fraction of LV among all study groups. Cardiac hypertrophy induced by co-administration of NE and ANP was attenuated by treatment with prazosin or atenolol. Conclusion: Both ANP and CNP potentiated α1- and β1-adrenergic receptor-mediated cardiac hypertrophic response to continuously infused NE in rats, suggesting a possible pro-hypertrophic action of NPs on the heart.