Age-Related Changes in Catecholaminergic Nerve Fibers of Rat Heart and Coronary Vessels

Abstract

Background: Age-related changes of catecholaminergic nerve fibers supplying the myocardium and the coronary vessels were studied in adult and in old rats. Objective: The purpose of this study was to investigate whether there are quantitative changes in myocardial and/or coronary catecholaminergic nerve fibers and related neurotransmitters. Methods: Samples of myocardium and/or coronary vessels were studied by means of glyoxylic acid induced fluorescence, aldehyde-induced fluorescence, and neuropeptide Y immunoreactivity. All morphological results were submitted to quantitative analysis of images. Biochemical dosage of proteins and of norepinephrine was also performed, and morphological data were compared with biochemical ones. Finally, all data were subjected to statistical analysis. Results: Our findings are indicative of an age-related decrease of all types of fluorescent sympathetic nerve fibers in rat heart and coronary arteries. Moreover, our data show that aging induces a strong decrease of norepinephrine levels in tissue homogenates of rat heart and coronary vessels. The majority of the catecholaminergic nerve fibers that show strong age-related changes are not contiguous with contractile cells of myocardium and/or of vascular wall. In fact, these fibers are located in adventitial (or epicardial) and in endothelial (or endocardial) layers. Conclusion: The decrease of the catecholaminergic innervation of heart and coronary vessels of old rats can be in close relationships to the poor cardiac and/or coronary functions observed in old animals.

Expressions of cardiac sympathetic norepinephrine transporter and β1-adrenergic receptor decreased in aged rats

“…Therefore, it is reasonable that NET protein biosynthesis reduces during aging, which likely contributes to the reduced cardiac reuptake capacity of NE. Since NET is a component of sympathetic nerves, the recent report by Bruzzone et al(2003) of an age-related decrease of the sympathetic is consistent with the present finding of a lower NET density with age. The reduction in NET protein might also be at least partly due to a loss of the nerve terminals, even though the NET protein does not correlate with the innervation density in myocardium (Wright et al, 2006;Wehrwein et al, 2008).…”

Quantifying perivascular sympathetic innervation: Regional differences in male C57BL/6 mice at 3 and 20 months

“…Such measurements have been instrumental in establishing that impaired blood flow to skeletal muscle in older subjects is associated with enhanced sympathetic vasomotor tone (Dinenno and Joyner, 2006). As determined in rats using fluorescence histochemistry for catecholamines (with formaldehyde vapor or glyoxylic acid reaction), aging has been associated with an apparent reduction in perivascular sympathetic innervation of the heart (Bruzzone et al, 2003) and spleen (Felten et al, 1987). However there is little information with respect to how aging may affect innervation density of the peripheral vasculature, particularly in the mouse.…”

“…Earlier anatomical studies of how aging affects sympathetic innervation have often relied on rodents as a model system while evaluating internal organs such as the spleen (Felten et al, 1987), pancreas (Lindsay et al, 2006) and heart (Bruzzone et al, 2003). In contrast, relatively little attention has been given to the peripheral vasculature, nor has there been a standardized procedure for quantifying PSID.…”

“…In contrast, relatively little attention has been given to the peripheral vasculature, nor has there been a standardized procedure for quantifying PSID. Moreover, the preparation of tissue samples for evaluating sympathetic innervation often involves embedding and sectioning (Lindsay et al, 2006) or dehydration and heating (Bruzzone et al, 2003; Marshall, 1982; Saltzman et al, 1992). Such practices can dramatically alter tissue morphology from that which is manifested in the intact system.…”

Tako-tsubo cardiomyopathy is age-dependent in men, but not in women

“…An important explanation for the age related difference in prevalence of TTC in men, but not in women, may be differences in stress hormones that are also related to oestrogen status during life. In animal models, an age related decrease in noradrenergic nerve fibres and increase of catecholamine levels with ageing is observed [7]. This means that theoretically both younger men and women may have an increased risk of a TTC.…”