Refeeding hypertension in dietary obesity
Ernsberger, P.; Nelson, D.O.
American Journal of Physiology 254(1 Pt 2): R47-R55
1988
ISSN/ISBN: 0002-9513 PMID: 3337269 Document Number: 310802
a novel model of nutritionally induced hypertension in the rat is described. Dietary obesity was produced by providing sweet milk in addition to regular chow, which elicited a 52% increase in caloric intake. Despite 54% greater body weight gain and 139% heavier retroperitoneal fat pads, 120 days of overfeeding failed to increase systolic pressure in the conscious state (125 .+-. 8 vs. 121 .+-. 4 mmHg in chow-fed controls) or mean arterial pressure under urethan anesthesia (71 .+-. 4 vs. 63 .+-. 3 mmHg). In contrast, mild hypertension developed in intermittently fasted obese animals (a 21-mmHg increase in systolic blood pressures measured in the conscious state and a 16-mmHg increase in mean arterial pressure under anesthesia relative to chow-fed controls). The first 4-day supplemented fast was initiated 4 wk after introduction of sweet milk, when the animals were 47 g overweight relative to chow-fed controls. Thereafter, 4 days of starvation were alternated with 2 wk of refeeding for a total of 4 cycles. A rapid fall in systolic blood pressure (12 .+-. 2 mmHg at 2 days) accompanied the onset of supplemented fasting and was maintained thereafter (2.7 .+-. 2.6 mmHg further decrease during the latter half of the fast). With refeeding, blood pressure rose precipitously (13 .+-. 3 mmHg in the 1st 2 days), despite poststarvation anorexia. Blood pressure tended to rise slightly over the remainder of the realimentation period (5.2 .+-. 2.8 mmHg). After the 4th supplemented fast, hypertension was sustained during 30 days of refeeding. Cumulative caloric intake in starved-refed rats fell within 2% of that in chow-fed controls. Despite normophagia, intermittently fasted rats gained 30% more weight and had 96% heavier retroperitoneal fat pads. Refeeding hypertension appeared to be due to increased sympathetic nervous activity, since 1) cardiac .beta.-adrenergic receptors were downregulated, as indicated by a 40% decrease in the maximum binding of [3H]dihydroalpranolol; and 2) the decrease in heart rate as a result of .beta.-blockade was enhanced. Refeeding hypertension in the dietary obese rat may be a potential animal model for some forms of human obesity-related hypertension.