Effect of caloric restriction on cardiac reactivity and beta-adrenoceptor concentration

Abstract

The effect of a 21-day program of caloric restriction on cardiac reactivity and beta-adrenoceptor number was investigated in male Sprague-Dawley rats. Rats on the restricted diet (Restricted) exhibited significant decreases in body weight, epididymal fat pad, and retroperitoneal fat pad weight as well as the percent of body fat represented by these adipose tissue depots when compared with rats fed ad libitum (Fed). Fed rats exhibited significantly increased total heart weight and total heart protein, but the percent cardiac protein and ratio of heart weight to body weight were similar in Fed and Restricted rats. Isolated atria from Fed and Restricted rats developed similar chronotropic and inotropic responses over a range of isoproterenol concentrations. Although total beta-adrenoceptor number (fmol/heart) was greater in Fed rats, the concentration of beta-adrenoceptors (fmol/mg protein) was remarkably similar regardless of the dietary regimen. Therefore, despite significant decreases in body weight, body fat, and heart weight, the myocardium of Restricted rats maintained the capability of responding to isoproterenol as that of Fed rats, the mechanism of which is at least partially mediated through maintenance of beta-adrenoceptor concentration.

Effect of long-term food restriction on cardiac mechanics

“…Earlier studies have shown that ␤-adrenergic sensitivity was enhanced in adipose tissue (5) and reduced in vascular smooth muscle (18). In the atria, short-term FR (11,18), but not protein deficiency (3), enhanced the sensitivity to ␤-adrenergic stimulation. In the isolated working heart, protein-calorie malnutrition increased both the sensitivity and responsiveness to ␤-adrenergic stimulation (13).…”

“…Not all changes induced by FR, however, enhance the aging phenotype. Short-term FR (11,18) increased the inotropic response to ␤-adrenergic stimulation in the atria. It also increased the inotropic and chronotropic responsiveness of the isolated working heart preparation to ␤-adrenergic agonists (13).…”

Assessment of Animal Models for Investigating the Cardiovascular Adaptations to Obesity

“…While some cardiovascular data arc available for each model reviewed, the spontaneously obese rat has been most extensively characterized. Biochemical adaptations of the myocardium to exper imental obesity have been reported [26,27,47], but this area has not been investigated extensively. The combined effects of obesity and hypertension upon the heart have been observed recently in the aorticcoarcted, obese rat, which may serve in the future as a useful model for investigating the basis of heart fail ure that occurs when these disorders arc observed concurrently in the clinical setting.…”

“…Of initial importance was the ability of the cardiac tissue to de velop contractile force through catechol amine stimulation, especially since the obese human heart exhibits reduced contractile in dices, often leading to cardiac failure [25]. Through a combination of in vitro analyses, cardiac (3-adrenoceptor concentration (Bmax) and affinity, as well as cardiac reactivity to exogenous isoproterenol were determined [26]. Obese rats exhibited increased cardiac weight and total cardiac protein as discussed earlier, but ventricular Bmax was unaffected [26].…”

“…Through a combination of in vitro analyses, cardiac (3-adrenoceptor concentration (Bmax) and affinity, as well as cardiac reactivity to exogenous isoproterenol were determined [26]. Obese rats exhibited increased cardiac weight and total cardiac protein as discussed earlier, but ventricular Bmax was unaffected [26]. The chronotropic and inotropic re sponse to isoproterenol resulted in similar effective concentrations of agonist required to produce a 50% maximal response, but a statistical trend was apparent for decreased sensitivity toward rate and tension develop ment in hearts from obese rats.…”