Basic Science and Experimental StudiesPreserved Norepinephrine Reuptake but Reduced Sympathetic Nerve Endings in Hypertrophic Volume-Overloaded Rat Hearts
Section snippets
Experimental Animals
The experiments were performed in male Wistar rats (Thomae, Biberach/Riss, Germany) and conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996) and was officially approved by the authorities at the Regierungspräsidium Karlsruhe, Germany.
Induction of Congestive Heart Failure
AVS was performed in male Wistar rats by a modified method of Garcia and Diebold,13 as previously described.10 Rats with a body weight of about 180 g were
Baseline Characterization of Aorto-Caval Shunt Rats
Six weeks after induction of AVS, peripheral shunt volume was 84 ± 4% of abdominal aortic blood flow, corresponding to a central shunt volume of approximately 55% of total cardiac output. The animals presented a doubled left ventricular end-diastolic pressure, marked left ventricular hypertrophy, and an increased lung wet weight as compared to SH rats, indicating a severe pulmonary congestion (Table 1). Furthermore, signs of more severe CHF such as ascites, or pleural effusions were observed at
Discussion
In the present study, we demonstrate that depletion of cardiac NE stores in volume overload–induced heart failure is caused by a reduction of sympathetic nerve fibers within the hypertrophic left ventricle and not by an impairment of NE reuptake, as it was shown previously in pressure overload.2 Experimental CHF was induced by infrarenal AVS, resulting in biventricular myocardial hypertrophy and overt heart failure. In contrast to other established animal models of heart failure, a major
Conclusions
Depletion of cardiac NE stores in volume overload–induced CHF is caused by a reduction of cardiac sympathetic nerve fibers. In contrast to other forms of CHF, an impairment of NE reuptake does not mediate depletion of cardiac NE stores in volume overload.
Acknowledgment
The expert technical assistance of Silvia Harrack, Jutta Krebs, and Michaela Oestringer is gratefully acknowledged.
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Cited by (20)
Responses of PKCε to cardiac overloads on myocardial sympathetic innervation and NET expression
2018, Autonomic Neuroscience: Basic and ClinicalCitation Excerpt :Therefore, it is implied that PKCs might be a central regulatory signal molecule in the status, which is activated or not could result in the different types of the ECM and nerve remodeling. In present study, we investigated how an nPKC isoform, PKCε, which is not only predominantly expressed in nerve tissue (Tanaka and Nishizuka, 1994; Obis et al., 2015), but also in cardiomyocytes, interstitial cells, vascular endothelial and smooth muscle cell (Ding et al., 2011; Komatsu et al., 2012; Lin et al., 2015; Rybin et al., 2003; Stawowy et al., 2005; Steinberg et al., 2007), contributes to ECM deposition, nerve rejuvenation and sympathetic reuptake protein membrane expression through such two different remodeling of classical animal models that characterized by the opposing changes in type of cardiac hypertrophy, ECM, nerve patterning and reuptake capacity (Backs et al., 2001; Kimura et al., 2007; Kreusser et al., 2017; Kristen et al., 2006; Nyquist-Battie et al., 1996; Somsen et al., 1996). Our experiment data indicated that at 8 weeks after the surgery the cardiac overload models developed into HF with high sympathetic activity.
Psychosocial stress-related changes in gene expression of norepinephrine biosynthetic enzymes in stellate ganglia of adult rats
2009, Autonomic Neuroscience: Basic and ClinicalDifferential expression of cardiac neurotrophic factors and sympathetic nerve ending abnormalities within the failing heart
2008, Journal of Molecular and Cellular CardiologyCitation Excerpt :In pressure overload induced by thoracic aortic constriction (TAC), we previously observed an impaired NE re-uptake but no loss of sympathetic nerves [9], analogous to the early stage of salt-induced heart failure in DS rats. In contrast, a preserved NE re-uptake but a loss of sympathetic nerves were observed in volume overload [38]. A common feature of TAC- and salt-induced heart failure (DS rats) but not of volume overload is a marked activation of the endothelin system [38].
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J.B. was supported by a grant from the Young Investigator Program of the University of Heidelberg.