Reduced Cardiac Contractile Responsiveness to Isoproterenol in Obese Rabbits

Carroll, Joan F.; Jones, Alan E.; Hester, Robert L.; Reinhart, Glenn A.; Cockrell, Kathy; Mizelle, H. L.

doi:10.1161/01.hyp.30.6.1376

Cited by 47 publications

(58 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…12 We also found a reduced contractile response to forskolin in the isolated hearts of obese rabbits. 13 Taken together, these studies suggested that obesity in this model was associated with one or more defects in b-receptor second messenger signaling system.…”

Section: Introductionsupporting

confidence: 52%

β-Adrenoceptor density and adenylyl cyclase activity in obese rabbit hearts

2002

View full text Add to dashboard Cite

Objective: To determine whether decreased cardiac responsiveness to isoproterenol in obesity is associated with alterations in b-receptors and=or adenylyl cyclase activity. Animals and Design: After 12 weeks of control or ad libitum high-fat diets, left ventricular tissue from lean and obese female New Zealand white rabbits was assayed for b-receptor binding density (11 lean, 11 obese) and isoproterenol-stimulated adenylyl cyclase activity (eight lean, 10 obese). Measurements: Nonlinear least squares regression analysis was used to determine maximum density of b-receptors and receptor affinity for 125 I-iodocyanopindolol. Four-parameter logistic regression was used to determine minimum, maximum, slope and EC 50 for isoproterenol-stimulated adenylyl cyclase activity. Results: Obese rabbits had elevated resting blood pressure and heart rate, and higher ventricular weights. However, badrenoceptor density and affinity were not significantly different in lean and obese rabbits. Basal and maximum isoproterenolstimulated adenylyl cyclase activity did not differ between lean and obese rabbits. In addition, maximal stimulation in response to sodium flouride did not differ between lean and obese. EC 50 for isoproterenol-stimulated adenylyl cyclase activity did not differ between lean and obese rabbits. Conclusion: Obesity-related decreases in responsiveness of the isolated heart to isoproterenol are not associated with alterations in b-receptor density and affinity. In addition, adenylyl cyclase activity appeared unchanged in ventricular preparations from obese rabbits. Decreased responsiveness to isoproterenol in obesity may be due to defects downstream of adenylyl cyclase activation of cyclic AMP.

show abstract

Section: Introductionsupporting

confidence: 52%

β-Adrenoceptor density and adenylyl cyclase activity in obese rabbit hearts

2002

View full text Add to dashboard Cite

show abstract

“…We believe that this outcome was due to the reduced sample size since the percentage difference is similar to the significant differences that we have previously noted between lean and obese rabbits. 9,[26][27][28] Further, acutely measured BP was significantly lower in obese hydralazine-treated compared with obese controls (84.771.8 vs 90.271.5 mmHg, respectively, Pr0.05).…”

Section: Animal Characteristics (Groups Matched For Body Weight)mentioning

confidence: 81%

Hydralazine as antihypertensive therapy in obesity-related hypertension

2004

View full text Add to dashboard Cite

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.

show abstract

“…12 In addition, obese rabbit hearts exhibit mild systolic dysfunction with a reduced contractile responsiveness to isoproterenol. 14 To what extent the cardiac changes observed in obesity are due to ectopic fat storage is not clear. Indeed, as illustrated in Figure 2, the causes of cardiac dysfunction in obesity are complex.…”

Section: Ectopic Fat Storage In the Heartmentioning

confidence: 99%

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

et al. 2004

View full text Add to dashboard Cite

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.

show abstract

Reduced Cardiac Contractile Responsiveness to Isoproterenol in Obese Rabbits

Cited by 47 publications

References 22 publications

β-Adrenoceptor density and adenylyl cyclase activity in obese rabbit hearts

β-Adrenoceptor density and adenylyl cyclase activity in obese rabbit hearts

Hydralazine as antihypertensive therapy in obesity-related hypertension

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

Contact Info

Product

Resources

About