Blunted natriuretic response to an acute sodium load in obese hypertensive dogs.

Abstract

Several studies support the premise that there is a strong relation between obesity and high blood pressure. Although the mechanism for obesity-related hypertension has not yet been fully elucidated, recent studies have suggested that abnormalities in renal sodium handling may be involved in the pathogenesis of obesity-induced hypertension. The purpose of the present study was to determine the effects of an acute saline load on renal excretory function in dogs with obesity-induced hypertension and in normotensive lean dogs. Experiments were performed in two groups of conscious, chronically instrumented dogs. One group of dogs (obese) was fed a high-fat diet for 5-6 weeks, and the other group (lean) ate a normal diet. The body weight of the obese dog group (26.3 +/- 0.7 kg) was 45% higher than the lean dog group (18.1 +/- 0.3 kg). Mean arterial pressure averaged 126 +/- 2 mm Hg in the obese dogs and 100 +/- 1 mm Hg in the lean dogs. The lean dogs had an average heart rate of 104 +/- 7 beats per minute, whereas the obese dogs averaged 134 +/- 8 beats per minute. Plasma renin activity was also significantly higher in the obese dogs. Both groups of dogs were given 135 meq sodium chloride over 60 minutes via an intravenous infusion of isotonic saline. Sodium and water excretion increased significantly in response to the acute saline load. However, the natriuresis and diuresis was markedly attenuated in the obese hypertensive dogs. During the first 40 minutes of saline loading, the increase in sodium and water excretion was 50-70% lower in the obese hypertensive dogs. The results of the present study indicate that obese hypertensive dogs have a reduced capability to excrete an acute sodium load. This abnormality in renal sodium handling may play a role in the pathogenesis of obesity-induced hypertension.

Differential Metabolic Effects of Energy Restriction in Dogs Using Diets Varying in Fat and Fiber Content

“…Thus, a longer period of overfeeding, with greater body fat content of the animals may have changed the results observed following energy restriction in insulin and glucose, as well as other parameters measured in this study. While the decrease in blood pressures with weight reduction with either diet was expected (33), there was not a significant increase in blood pressure with weight gain during the 9-week ad libitum feeding period as we (40) and others (33) have previously reported in the dog. This may have been due to the fact that the gain in body weight following 9 weeks of the moderately high-fat diet was slight and only two of the animals had high levels of body fat (Table 2).…”

Abnormal pressure natriuresis in the dog model of obesity-induced hypertension.

“…4 -910 We have also recently reported that the obese hypertensive dog excretes significantly less sodium and water than normotensive control dogs in response to an acute saline load. 11 Furthermore, research indicates that obese hypertensive patients exhibit abnormal renal sodium handling. 14 Thus, it appears that the regulatory mechanisms responsible for control of sodium excretion and extracellular fluid volume may be altered in obesity-associated hypertension.…”

Blunted natriuretic response to a high-sodium meal in obese dogs. Role of renal nerves.

“…46 We have recently demonstrated that the natriuretic response to an acute sodium load is significantly attenuated in obese dogs. 7 Although the exact mechanism responsible for the blunted natriuretic response to an acute sodium load in obesity-hypertension is unknown, abnormalities in sodium-retaining systems such as renin-angiotensin and renal sympathetic nervous systems may be involved. 8 To quantify the role of renal nerves in the blunted response to an acute sodium load in obese dogs, we examined the changes in renal hemodynamics and sodium excretion in separate innervated and denervated kidneys simultaneously within the same dog.…”

“…5 Furthermore, we have recently demonstrated that the natriuretic response to an acute sodium load is significantly attenuated in obese dogs. 7 Although the exact mechanism responsible for the blunted natriuretic response to an acute sodium load in obesity hypertension is unknown, abnormalities in sodiumretaining systems such as renin-angiotensin and renal sympathetic nervous systems may be involved. 8 A possible role for renal nerves is supported by studies indicating that obesity is associated with increased activity of the sympathetic nervous system.…”