Pathogenesis of weight-related changes in blood pressure in dogs.

Abstract

We have previously shown that weight gain in the dog results in an increase in blood pressure. To study the pathogenesis of the rise in blood pressure associated with weight gain, we compared the serial changes in blood pressure, body weight, sodium balance, plasma volume, and three hormones known to affect sodium balance (norepinephrine, insulin, and aldosterone) in seven dogs fed a high fat diet for 6 weeks and seven dogs fed a control diet. The sodium content of both diets was equal. During a 2-week control period, no differences were noted between the two groups. Weight gain was associated with a progressive increase in blood pressure (mean pressure increased by 18.5±2.1 mm Hg in the high fat group) and plasma volume (plasma volume increased from 1,426±202 to 2,053±250 ml in the high fat group). Sodium retention occurred after 1 week of the high fat diet and persisted. Over the 6-week period, the dogs on the high fat diet increased their cumulative sodium balance by 2,024±462 meq versus an increase of only 289±97 meq for the dogs on the control diet. In the high fat diet group of dogs, there was a significant relation between change in cumulative sodium balance and the change in blood pressure and plasma volume. After 1 week of the high fat diet, norepinephrine was the only hormone that significantly increased from baseline. Over the next 5 weeks norepinephrine increased no further, whereas fasting insulin and aldosterone progressively increased. Over the entire study period, fasting insulin was the hormone that best correlated with the change in blood pressure observed in the high fat diet dogs. Thus, the change in blood pressure associated with weight gain in the dog is directly related to sodium retention. The observed change in sodium balance also appears to relate initially to a change in plasma norepinephrine concentration and later to a change in fasting insulin and aldosterone concentrations. (Hypertension 1989;13:922-928)

Obesity-induced hypertension. Renal function and systemic hemodynamics.

“…In the present study, fasting plasma insulin concentration increased twofold to threefold during 5 weeks of the high-fat diet, possibly as a compensation for insulin resistance. Previous studies have shown a positive correlation between blood pressure and plasma insulin in obese dogs 7 and in humans. 20 " 24 In addition, several acute studies have shown that insulin reduces sodium excretion, 2527 possibly by increasing reabsorption in the loop of Henle.…”

“…Their observations suggest that obesity is associated with increased cardiac output, possibly in excess of the increased flow to adipose tissue, and that the rise in blood pressure was accompanied by marked sodium and fluid retention. 7 -815 The mechanisms responsible for sodium and fluid retention, however, were not directly assessed in those studies. In the present study, we examined the changes in renal hemodynamics and tubular function responsible for altered sodium handling during a high-fat diet in dogs and quantitated changes in systemic hemodynamics using methods that allowed continuous monitoring of arterial pressure, cardiac output, heart rate, stroke volume, and total peripheral resistance on a beat-by-beat basis, 24 h/d.…”

“…Previous studies of the renin-angiotensin system in obesity have yielded conflicting results. Rocchini et al 7 found no change in plasma renin activity in obese dogs, whereas Tuck et al 34 reported that plasma renin activity was elevated in obese humans. In our studies, plasma renin activity was elevated more than twofold after 5 weeks of the high-fat diet despite marked sodium retention and increased extracellular fluid volume.…”

“…However, the mechanisms responsible for hypertension were not determined, and there has been very little effort in the past 50 years to further develop large-animal models of obesity. Rocchini and colleagues 7 - 8 have demonstrated that dogs fed a high-fat diet have many of the characteristics of obese humans, including hyperinsulinemia, insulin resistance, sodium retention, and hypertension. However, the physiological mechanisms that lead to sodium retention and hypertension during the development of obesity are still unclear.…”

Effects of weight loss on the cardiac parameters of obese dogs

“…As in this work, Brown et al (2007) observed that overweight dogs possessed higher reference range arterial pressures in relation to those of ideal body weight. As such, food restriction is considered an important non-pharmacological treatment for controlling arterial pressure, especially in dogs of excessive weight (Rocchini et al 1987, Rocchini et al 1989.…”