Studies are proposed to measure blood pressure chronically in different rat models of obesity and test the hypothesis that blood pressure becomes evaluated by changes in baroreflex sensitivity, cardiovascular reactivity, regional hemodynamics, or humoral regulation. Initial experiments will determine whether blood pressure becomes progressively elevated as rats gain weight following chemical or electrolytic lesions of the ventromedial hypothalamus, or prolonged feeding of high-fat and high-sugar diets, and compare the chronic time course of blood pressure changes with that occurring in Zucker """"""""fatty' and Koletsky obese SHR rats. If hyperphagia occurs during induction of obesity in any of the models being studied, effects of diets containing reduced salt will be compared to determine how much of the change in blood pressure is due to salt loading. Subsequently, other experiments will study effects of dietary caloric restriction on blood pressure changes occurring in the various rat models in order to explore the possibility that reduction in body weight would alleviate hypertension as it does in man. Since hyperinsulinemia commonly occurs in all obese rat models, its contribution to the associated hypertension will be assessed by using subdiabetogenic doses of streptozotocin or alloxan to reduce pancreatic insulin secretion. If significant elevations of blood pressure are detected in obese rats, terminal experiments will be done to determine whether changes in baroreflex sensitivity, cardiovascular reactivity, or regional hemodynamics contribute to the ensuing hypertension. Finally, other terminal experiments will also assess the extent to which sympathetic, vasopressin, and renin-angiotensin pressor mechanisms participate in regulating blood pressure in obese rats. By obtaining basic information on what happens to blood pressure in obese rats, these studies may identify models that would allow detailed examination of mechanisms underlying obesity hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL039383-03
Application #
3356182
Study Section
(SRC)
Project Start
1987-07-01
Project End
1992-04-30
Budget Start
1989-05-01
Budget End
1990-04-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Kansas
Department
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160
Bunag, R; Mellick, J; Allen, B (1999) Abated cardiovascular responses to chronic oral lisinopril treatment in conscious elderly rats. Am J Physiol 276:R1408-15
Bunag, R D; Davidow, L W (1996) Aging impairs heart rate reflexes earlier in female than in male Sprague-Dawley rats. Neurobiol Aging 17:87-93
Bunag, R D; Meyer, M; Vansell, N et al. (1996) Conscious obese rats have impaired reflex bradycardia and enhanced norepinephrine sensitivity. Am J Physiol 271:R654-60
Okada, M; Bunag, R D (1994) Insulin acts centrally to enhance reflex tachycardia in conscious rats. Am J Physiol 266:R481-6
Davidow, L W; Schmitz, T M; Bunag, R D (1994) Aging enhances serotonergic cardiovascular blockade by ketanserin in conscious rats. Aging (Milano) 6:239-48
Okada, M; Bunag, R D (1994) Selective enhancement in SHR of hypotension and bradycardia caused by NTS-injected serotonin. Am J Physiol 266:R599-605
Bunag, R D; Teravainen, T L (1991) Waning cardiovascular responses to adrenergic drugs in conscious ageing rats. Mech Ageing Dev 61:313-26
Bunag, R D; Teravainen, T L (1991) Tail-cuff detection of systolic hypertension in different strains of ageing rats. Mech Ageing Dev 59:197-213
Bunag, R D; Krizsan-Agbas, D; Itoh, H (1991) Sympathetic activation by chronic insulin treatment in conscious rats. J Pharmacol Exp Ther 259:131-8
Barringer, D L; Bunag, R D (1991) Autonomic regulation of reflex bradycardia in rats declines with age. Exp Gerontol 26:65-75

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