Hypertension, cardiac hypertrophy, and neurohumoral activity in a new animal model of obesity

Carroll, Joan F.; Dwyer, Terry; Grady, Andrew W.; Reinhart, Glenn A.; Montani, Jean‐Pierre; Cockrell, Kathy; Meydrech, Edward F.; Mizelle, H. L.

doi:10.1152/ajpheart.1996.271.1.h373

Cited by 64 publications

(100 citation statements)

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“…In the rabbit model of obesity, a 50% gain in body weight led to an increase in dry weight of the right and left ventricles by about 70 and 50%, respectively, and to an increase in protein content by about 50% in both right and left ventricles. 4 Since there were no significant alterations in total DNA content, these data suggest that weight gain causes cardiac myocyte hypertrophy. There was also a nearly two-fold increase of fat weight for both ventricles, which appears to be caused primarily by increased depots in the fat pads around the base of ventricles.…”

Section: Ectopic Fat Storage In the Heartmentioning

confidence: 84%

“…In the last few years, [3][4][5][6][7][8] a new animal model of obesity, the rabbit fed a high-fat diet has allowed us to study many of the mechanisms of obesity-associated cardiovascular pathologies. Ad libitum access to high-fat diet for 8-12 weeks led to a more than three-fold increase in percent fat content determined by carcass analysis and lipid extraction, from 10% in lean rabbits to about 34% in obese rabbits.…”

Section: Introductionmentioning

confidence: 99%

“…8 Obese rabbits also exhibit neurohormonal changes with hyperinsulinemia, elevated plasma triglyceride levels and increased activity of the sympathetic nervous system and the reninangiotensin system. 4 Finally, obese rabbits show abnormal sodium handling with marked sodium retention during the development of obesity despite an elevated glomerular filtration rate (GFR). 6,7 Similar findings are observed when dogs are fed a high-fat diet for several weeks.…”

Section: Introductionmentioning

confidence: 99%

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Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases

et al. 2004

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In humans and most animal models, the development of obesity leads not only to increased fat depots in classical adipose tissue locations but also to significant lipid deposits within and around other tissues and organs, a phenomenon known as ectopic fat storage. The purpose of this review is to explore the possible locations of ectopic fat in key target-organs of cardiovascular control (heart, blood vessels and kidneys) and to propose how ectopic fat storage can play a role in the pathogenesis of cardiovascular diseases associated with obesity. In animals fed a high-fat diet, cardiac fat depots within and around the heart impair both systolic and diastolic functions, and may in the long-term promote heart failure. Accumulation of fat around blood vessels (perivascular fat) may affect vascular function in a paracrine manner, as perivascular fat cells secrete vascular relaxing factors, proatherogenic cytokines and smooth muscle cell growth factors. Furthermore, high amounts of perivascular fat could mechanically contribute to the increased vascular stiffness seen in obesity. Finally, accumulation of fat in the renal sinus may limit the outflow of blood and lymph from the kidney, which would alter intrarenal physical forces and promote sodium reabsorption and arterial hypertension. Taken together, ectopic fat storage in key target-organs of cardiovascular control may impair their functions, contributing to the increased prevalence of cardiovascular diseases in obese subjects.

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Section: Ectopic Fat Storage In the Heartmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases

et al. 2004

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“…5 This observation is supported by data which show a positive linear relationship between BP and body mass index even in the normotensive range, 6 and also by data demonstrating that obese-normotensive individuals almost always reduce BP when they lose weight. 7,8 In contrast, it is possible to study hypertension-independent effects of obesity on cardiovascular function with an animal model of diet-induced obesity, 9 by utilizing a longitudinal analysis wherein a pre-obese BP is determined and subsequently maintained during obesity development. However, the choice of antihypertensive treatment is problematic.…”

Section: Introductionmentioning

confidence: 99%

“…21,22,15,16 Use of hydralazine as antihypertensive therapy in an obesity-hypertension model is further complicated by the fact that potential side effects are similar to physiological changes often seen in obesity (e.g., tachycardia and activation of the reninangiotensin system (RAS)). 9,23,24 Therefore, the purposes of this study were two-fold. First, using the rabbit model, we sought to determine whether the use of hydralazine as an antihypertensive therapy would exacerbate cardiovascular and hormonal alterations already present in obesity.…”

Section: Introductionmentioning

confidence: 99%

Hydralazine as antihypertensive therapy in obesity-related hypertension

2004

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OBJECTIVE:The objectives were two-fold: (1) determine whether the use of hydralazine as antihypertensive therapy during obesity development exacerbated obesity-related cardioacceleration and hormonal abnormalities; (2) determine whether the absence of hypertension in obesity attenuated obesity-related abnormalities in hemodynamics, cardiac hypertrophy, and hormonal profile. DESIGN: Female New Zealand White rabbits were divided into lean control (n ¼ 12), lean hydralazine-treated (n ¼ 9), obese control (n ¼ 11), and obese hydralazine-treated (n ¼ 8) groups. Pretreatment mean blood pressure (BP) and heart rate (HR) were determined using telemetry. Pretreatment BP was maintained during 12 weeks of obesity development using hydralazine. MEASUREMENTS: Chronically measured BP and HR; plasma/blood volume; wet and dry ventricular weights; body fat/water; and hormonal profile (plasma renin activity, aldosterone, cortisol, atrial natriuretic peptide, adrenaline, and noradrenaline). RESULTS: Hydralazine treatment in obese animals attenuated obesity-related renin-angiotensin system (RAS) activation. In contrast, RAS was activated in lean hydralazine, as indicated by increased plasma aldosterone. The absence of hypertension in obese hydralazine did not result in attenuation of cardioacceleration, cardiac hypertrophy, or intravascular volumes. CONCLUSIONS: Hydralazine treatment in obese rabbits did not exacerbate obesity-related cardiovascular and hormonal alterations. Cardioacceleration and cardiac hypertrophy persisted in obese hydralazine despite BP control, suggesting hypertension-independent effects of obesity on these variables. Hydralazine's effects on RAS activation differed in lean and obese rabbits, suggesting that the systemic effects of hydralazine as a control therapy in evaluation of antihypertensive medications may differ depending on the underlying pathology.

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Central Nervous System Dysfunction in Obesity-Induced Hypertension

et al. 2014

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The activation of the sympathetic nervous system is a major mechanism underlying both human and experimental models of obesity-related hypertension. While insulin and the adipokine leptin have long been thought to contribute to obesity-related neurogenic mechanisms, the evidence is now very strong that they play a major role, shown particularly in animal studies using selective receptor antagonists. There is not just maintenance of leptin's sympatho-excitatory actions as previously suggested but considerable amplification particularly in renal sympathetic nervous activity. Importantly, these changes are not dependent on short-term elevation or reduction in plasma leptin or insulin, but require some weeks to develop indicating a slow "neural adaptivity" within hypothalamic signalling. These effects can be carried across generations even when offspring are raised on a normal diet. A better understanding of the underlying mechanism should be a high research priority given the prevalence of obesity not just in the current population but also for future generations.

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Hypertension, cardiac hypertrophy, and neurohumoral activity in a new animal model of obesity

Cited by 64 publications

References 0 publications

Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases

Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases

Hydralazine as antihypertensive therapy in obesity-related hypertension

Central Nervous System Dysfunction in Obesity-Induced Hypertension

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