Alteration of messenger RNA and protein levels of cardiac alpha(1)-adrenergic receptor and angiotensin II receptor subtypes during aging in rats

Abstract

S everal receptor systems coexist in the heart, including the adrenergic receptor (AR) and the angiotensin II receptor (ATR). Among the cardiac adrenoceptor subtypes, it is well known that beta (β)-AR is predominant with respect to mediating positive inotropic and chronotropic effects (it accounts for approximately 75% of the inotropic response); however, a vast body of evidence has accumulated showing that the alpha(1)-AR (α 1 -AR) also plays an important role in causing positive inotropic effects (it accounts for approximately 25% of the inotropic response). A recent finding (1) indicates that, in addition to the regulation of myocardial contractility, α 1 -AR is involved in mediating the hypertrophic response of cardiomyocytes. Moreover, it has been shown that the ATR not only influences hemodynamics, but also regulates the growth and hypertrophic response of cardiomyocytes, vascular smooth muscle cells and fibroblasts, which are related to cardiovascular remodelling and functional alteration.The endogenetic ligands of α 1 -AR are noradrenaline and adrenaline, while the ATR is always activated by angiotensin II (Ang II). According to its pharmacological characteristics, α 1 -AR is divided into three subtypes: α 1A -AR, α 1B -AR and α 1D -AR. ATRs can be grouped into AT 1 R and AT 2 R. Structural and functional alterations in the senile heart have been associated with an activated sympathetic system and a regional cardiac renin-angiotensin system. However, the influence of aging on the expression of cardiac α 1 -AR and ATR subtypes has remained uncertain. Previous investigations (2-4) focused on comparing the expression of α 1 -AR and ATR subtypes between young adulthood and senescence, but to date, limited information has been expeRImeNtAl studIes ©2009 Pulsus Group Inc. All rights reserved BACKGROUND: Structural and functional alterations in the senescent heart have been associated with an activated sympathetic nervous system and a regional cardiac renin-angiotensin system. To date, however, limited information related to their expression alteration during the whole procress of growth and development has been reported. OBJECTIVES: To examine the expression of alpha(1)-adrenergic receptor (α 1 -AR) and angiotensin II receptor (ATR) subtypes in the left ventricle of hearts from young adult, middle-aged, presenescent and senescent rats. METHODS: Semiquantitative reverse transcriptase polymerase chain reaction and Western blot were used to quantitate the messenger RNA and protein of α 1 -AR and ATR subtypes, respectively, in the left ventricles of three-(young adult), 12-(middle age), 18-(presenescent) and 24-month-old (senescent) Wistar rats. RESULTS AND CONCLUSIONS: α 1A -AR expression decreased gradually with age, and α 1D -AR expression was repressed in middle age and presenescence, while the expression of α 1B -AR remained unchanged during senescence. AT 1 R expression was unaffected by aging from young adulthood to presenescence, but exhibited a remarkable upregulation in senescence. There were no signific...

Immune-inflammatory dysregulation modulates the incidence of progressive fibrosis and diastolic stiffness in the aging heart

“…Studies have suggested roles for reactive oxygen [19] and the RAS [24, 53] paralleling the effectors studied in our acute models of reactive interstitial fibrosis [28, 31]. Importantly, several studies, done primarily in the rat, suggest that the local or intrinsic RAS is activated in the aging heart [17, 18, 22, 23, 53]. A recent study in mice utilized mass spectroscopy to demonstrate a significant augmentation of local Ang II in the aging mouse heart [19].…”

“…Furthermore, there is substantial evidence that the aging heart has an augmented endogenous RAS, including ACE1 and ATR-1 in old rats [17, 18] and cardiac Ang II levels in old mice [19] and rats [20]. Hydroxyproline levels, a marker for collagen content, have been known for many years to be elevated in the old rat heart [21].…”

Cardiac aging – a review

“…According to their results impaired gene transcriptional activity was responsible for the decreased expressions. Their hypothesis was that these alterations contribute to the maintenance of normal contractile function in the senescent heart by compensating cardiac hypertrophy and preserving coronary blood flow [19]. Therefore, these changes might be an adaptive response to aging-associated alterations in the cardiovascular system.…”

“…AT1 receptors mediate oxidative stress, fibrosis, myocardial hypertrophy, even age-associated hypertrophy, and a number of actions, which contribute to age-related cardiac remodeling. On the other hand, activation of AT2 receptors is considered to antagonize the AT1 receptor-mediated effects [19]. Moreover, AT2 receptors are suggested to be responsible for a benignant form of cardiovascular remodeling: during AT2 receptor stimulation and AT1 receptor blockade Jones et al reported antigrowth effects on cardiac hypertrophy, fibrosis, and aortic hypertrophy in aged rat hearts [24].…”

“…Moreover, AT2 receptors are suggested to be responsible for a benignant form of cardiovascular remodeling: during AT2 receptor stimulation and AT1 receptor blockade Jones et al reported antigrowth effects on cardiac hypertrophy, fibrosis, and aortic hypertrophy in aged rat hearts [24]. In addition, long-term medical inhibition of the RAS was significantly protective against the deleterious process of aging on the cardiovascular system: decrease in high Cardiac senescence © Springer-Verlag 2/2011 Eur Surg blood pressure, reduced oxidative stress, and decreased age-associated LV hypertrophy were reported [19,25,26]. These findings confirm the significance of RAS in the development of age-related cardiac alterations.…”