Rat strain-related differences in myocardial adrenergic tone and the impact on cardiac fibrosis, adrenergic responsiveness and myocardial structure and function

Abstract

Sprague-Dawley (SD) rats have been reported to have a higher sympathetic activity than Wistar-Kyoto (WKY) rats. In the present study we sought to determine if these rat strain-related differences in sympathetic activity exist at a myocardial level and whether they translate into changes in cardiac fibrosis, contractile responsiveness to adrenergic agonists, and cardiac structure and function. Coronary effluent noradrenaline concentrations, as determined in isolated, perfused heart preparations, were higher in 5-month-old SD as compared to age-matched WKY male rats. This difference was accompanied by higher resting heart rates in SD rats as assessed in vivo. However, increases in myocardial noradrenaline release in SD rats did not translate into enhanced myocardial fibrosis, cardiac hypertrophy or remodeling, changes in basal ventricular systolic and diastolic function, or to down-regulation of inotropic responses to the beta-adrenoreceptor agonists, noradrenaline, isoproterenol and dobutamine. Although age-matched male SD rats were heavier, no differences in absolute heart weights were noted between rat strains. Moreover, left ventricular (LV) posterior wall thickness as assessed by echocardiography, as well as cardiac myocyte dimensions as determined by laser scanning confocal microscopy were similar between rat strains. Furthermore, LV internal diameters as determined in vivo, as well as LV diastolic volume intercept determined in isolated, perfused heart preparations were similar between rat strains. Increases in myocardial noradrenaline release in SD rats also did not translate into differences in LV systolic chamber and myocardial function as assessed in vivo (LV endocardial and midwall fractional shortening) and at controlled loads and heart rates ex vivo (the slope of the LV developed pressure-volume relation determined). Likewise, neither myocardial hydroxyproline content nor LV chamber stiffness as assessed by the slope of the LV end-diastolic pressure-volume relation were different in SD and WKY rats. In conclusion, rat strain-related differences in cardiac adrenergic tone do indeed exist, but in young animals these differences do not translate into cardiac phenotypes known to contribute to progressive cardiac dysfunction.