Dietary-Induced Obesity Hastens the Progression From Concentric Cardiac Hypertrophy to Pump Dysfunction in Spontaneously Hypertensive Rats

Abstract

Abstract-We explored whether dietary-induced obesity hastens the transition from concentric left ventricular (LV) hypertrophy to pump dysfunction in spontaneously hypertensive rats (SHRs) and the mechanisms thereof. After feeding rats a diet for 4 to 5 months, obesity was induced in SHRs and Wistar-Kyoto (WKY) control rats. Obesity was not associated with abnormal blood glucose control (glycosylated hemoglobin) or with increases in systolic blood pressure. However, in SHRs, but not in WKY rats, obesity was associated with a reduced LV chamber systolic function, as determined by echocardiography, and in isolated perfused heart studies. A marked increase in LV end diastolic diameter and a right shift in the LV diastolic pressure-volume relation were noted in obese SHRs but not in obese WKY rats. Moreover, LV intrinsic myocardial systolic function, as determined from the slope of the linearized LV systolic stress-strain relationship (LV myocardial end systolic elastance), was markedly reduced in obese as compared with lean SHRs, whereas LV myocardial end systolic elastance was maintained in obese WKY rats. Obesity increased LV weight, cardiomyocyte width, cardiomyocyte apoptosis (TUNEL), the activity of myocardial matrix metalloproteinases (zymography), and serum leptin concentrations in SHRs but not in WKY rats. In conclusion, SHRs are susceptible to the adverse effects of dietary-induced obesity on the heart, an effect that hastens the progression from concentric LV hypertrophy to pump dysfunction independent of blood pressure changes or alterations in glycosylated hemoglobin. This effect may be mediated through a proclivity of SHRs to developing both obesity-induced effects on cardiomyocyte apoptosis and activation of myocardial collagenases through leptin resistance and obesity-induced hypertrophy. Key Words: obesity Ⅲ ventricular function Ⅲ rats inbred spontaneously hypertensive rats Ⅲ dilatation Ⅲ ventricular remodeling O besity is an independent risk factor for heart failure. [1][2][3] As adjustments for cardiac systolic chamber function abolish the relationship between obesity and heart failure, 2 it is possible that heart failure in obesity is caused by pump dysfunction rather than diastolic abnormalities. There is increasing evidence from both human 4,5 and animal studies 6,7 that obesity is associated with myocardial contractile disturbances. However, a cause-effect relationship between obesity and cardiac systolic dysfunction is controversial. Indeed, weight loss produced by lifestyle modification or gastric bypass does not influence left ventricular (LV) myocardial systolic dysfunction. 8,9 Moreover, although some studies have reported a decreased LV pump function associated with obesity, 10 -13 the majority indicate a normal or even increased LV pump function. 4,5,14 -22 Because pump dysfunction is an established predictor of the development of heart failure, 23 clarity on the role of obesity in the development of pump dysfunction is required.Obesity may augment the impact of hypertension on LV hyp...

Hypertensive left ventricular hypertrophy risk: beyond adaptive cardiomyocytic hypertrophy

“…Hopefully, wiser correction by diet therapy will prevent these severe consequences. In addition, it has been shown that Western diets giving rise to a metabolic syndrome phenotype (obesity, type 2 diabetes, dyslipidemia) also exacerbate myocardial remodelling changes in experimental genetic hypertensive rats with LVH [66,67].…”

Impact of Aldosterone Receptor Blockade on the Deleterious Cardiac Effects of Adrenergic Activation in Hypertensive Rats

“…17 Rats were placed in restrainers for an hour a day on 5 separate days before the first measurement to habituate them to the procedure.…”

“…As changes in cardiomyocyte length are a slow process, 16 they are unlikely to occur within a 5-day period; hence, cardiomyocyte morphology was not assessed in rats in the acute model. Cardiomyocytes were isolated as previously described, 17 from hearts arrested in diastole by the infusion of a high dose (16 mM) of potassium chloride. 27,28 For image analysis, cells were diluted in physiological saline solution containing 0.01% bromophenol blue (The Coleman and Bell, Co, Medina, OH).…”

Hypertension in Africa: Redressing the burden of cardiovascular disease using cost-effective nonpharmacological approaches

“…In order to provide further proof of principle, we therefore performed a prospective study in an animal model of hypertension. (51) In this regard, a dietary intervention that promoted visceral obesity similarly resulted in a marked further increase in left ventricular weight in hypertensive, but no effect on left ventricular weight in normotensive rats, the consequence being that in the hypertensive rats, cardiac dilatation and pump dysfunction occurred. (51) These data lend further support for the concept that an excess adiposity may enhance the adverse effects of BP on cardiovascular damage.…”

“…(51) In this regard, a dietary intervention that promoted visceral obesity similarly resulted in a marked further increase in left ventricular weight in hypertensive, but no effect on left ventricular weight in normotensive rats, the consequence being that in the hypertensive rats, cardiac dilatation and pump dysfunction occurred. (51) These data lend further support for the concept that an excess adiposity may enhance the adverse effects of BP on cardiovascular damage. Thus, although obesity may not account for a significant proportion of the variability of BP in groups of African ancestry, the purpose of targeting obesity may be to decrease the adverse impact of BP on the heart.…”