Influence of Age on the Inotropic Response to Acute Ethanol Exposure in Spontaneously Hypertensive Rats

Abstract

Acute ethanol exposure depresses cardiac electromechanical function, whereas chronic ethanol consumption leads to the development of a specific myopathic state. Chronic hypertension and aging have similar effects in the impairment of myocardial function. However, little is known about the effects of ethanol on cardiac mechanical function in hypertension. We studied the effect of age on baseline mechanical properties and the inotropic response to clinically relevant concentrations of ethanol (18 to 71 mmol/L) using papillary muscles from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) at 10 and 25 weeks of age. Mechanical parameters measured were peak tension developed, time to peak tension, time to 90% relaxation, and maximal velocities of tension development and tension decline. SHR exhibited elevated systolic pressure and body weight as well as cardiomegaly and hepatomegaly at 10 and 25 weeks of age. Baseline mechanical properties were similar in SHR and WKY muscles at 10 weeks, whereas at 25 weeks, SHR muscles developed less tension, and both maximal velocities of tension development and tension decline were markedly depressed. Ethanol exposure produced concentration-dependent negative inotropic effects in both groups at both ages. Ethanol (> 18 nmol/L) decreased peak tension developed in both groups at 10 weeks, although higher concentrations were required at 25 weeks. The negative inotropic effect of ethanol resulted in the shortening of time to 90% relaxation in both groups at 10 weeks and was associated with a slowing of maximal velocities of both tension development and tension decline. The results suggest that aging depresses baseline mechanical properties when coupled with hypertension. In addition, the magnitude of the negative inotropic effect of ethanol was attenuated in both groups at 25 weeks of age.

Basal and Ethanol-Induced Cardiac Contractile Response in Lean and Obese Zucker Rat Hearts

“…The experimental procedures outlined in this investigation were approved by Wayne State University Animal Investigation Committee and have been previously described [4]. Age-matched female Zucker obese (fa/fa) and lean (fa/?)…”

“…PTD was normalized to the respective control values and presented as a percent change to minimize intermuscle variance. The following parameters were measured: developed tension; time to peak tension (TPT); time to 90% relaxation (RT 90 ) and the maximum velocities of tension developed and decline in tension (BVT) [3,4].…”

“…Moreover, excessive ethanol may be associated with alcoholic cardiomyopathy, a clinical condition that leads to ventricular dysfunction, hypertension and heart failure [2,29]. Although ethanol has been reported to both improve and impair cardiac function in human and experimental animals, it depresses contractile function unequivocally in isolated cardiac preparations [1,[3][4][5]8]. Recent studies suggested that changes at the single cardiac myocyte level, such as myofibril Ca 2+ sensitivity, plasma membrane properties and intracellular Ca 2+ , are responsible for ethanol-induced myocardial alteration [5,9,18,25].…”

Influence of Age on Contractile Response to Insulin-Like Growth Factor 1 in Ventricular Myocytes From Spontaneously Hypertensive Rats

“…Systolic blood pressures and body weights were obtained on a weekly basis by using the tail-cuff method and a standard laboratory balance, respectively. 26 …”

“…2,24 Development of ventricular dysfunction also appears to increase with age or the duration of hypertension. 25,26 Thus, the present study was designed to evaluate the effect of IGF-1 on cardiac contractility/Ca 2ϩ metabolism in WKY and SHR at an advanced age (36 weeks).…”