ABNORMAL PRESSURE NATRIURESIS IN THE DOG-MODEL OF OBESITY-INDUCED HYPERTENSION

Obesity is considered to be a major factor in the pathogenesis of hype rtension in industrialized countries. Recent studies have suggested th at the kidneys may play an important role in the development of obesit y-induced hypertension. The purpose of this study was to determine whe ther obesity-induced hypertension is associated with abnormalities in the pressure-natriuresis relation. Renal function studies were perform ed in anesthetized control dogs (body weight, 20.2+/-0.8 kg) and obese dogs (body weight, 26.4+/-0.7 kg) that were maintained on a high-fat diet for 5 to 6 weeks. Mean arterial pressure averaged 122+/-5 mm Hg i n the control group (n=6) and 148+/-7 mm Hg in the obese group (n=8). The effects of renal perfusion pressure on renal hemodynamics as well as sodium and water excretions were examined at five levels of renal p erfusion pressure ranging from 75 to 165 mm Hg. Pressure-natriuretic a nd diuretic responses were reduced in the obese dogs by 40% to 50%. Th e renal blood flow and glomerular filtration rate autoregulatory respo nses and fractional lithium excretion responses to changes in renal pe rfusion pressure were similar in the control and obese dog groups. Ass ociated with the attenuated natriuretic response to renal perfusion pr essure in the obese dogs were significant elevations in plasma renin a ctivity (4.3+/-1.6 versus 1.6+/-0.5 ng angiotensin I/mL per hour), pla sma aldosterone concentration (34.4+/-6.4 versus 15.3+/-3.2 ng/dL), an d plasma insulin concentration (30.5+/-6.8 versus 20.9+/-2.9 IU/mL). T he results of this study establish that obesity-induced hypertension i n the dog is associated with a shift in the pressure-natriuresis relat ion. The underlying mechanism responsible for the abnormal pressure-na triuresis relation in this model of obesity may be due to activation o f various sodium-retaining systems such as the renin-angiotensin-aldos terone system.