Changes in skeletal muscle vascular resistance with weight gain: associations with insulin and sympathetic activity.

OBJECTIVE: This study was designed to characterize changes in peripheral vascular resistance with weight gain, and whether these changes are correlated with insulin and/or sympathetic activity. RESEARCH METHODS AND PROCEDURES: Femoral vascular resistance (FVR), mean arterial pressure, heart rate, and plasma insulin were measured before and during overfeeding in seven dogs with unilateral lumbar ganglionectomy (L3 to L6). Measurements were taken standing and while walking on a treadmill. RESULTS: There was a significant main effect of weight gain to increase mean arterial pressure (16.5+/-8.4 mmHg and 12.5+/-6.8 mmHg increase for standing and walking baseline, respectively) and heart rate (increase from week 1 of 31.6+/-10.6 beats/minute standing and 38.3+/-9.1 walking beat/minute). FVR increased immediately with overfeeding/ weight gain [standing: denervated (DNX):1.32+/-0.3 to 2.34+/-0.5; intact: 0.88+/-0.17 to 1.9+/-0.33 mmHg/mL.min(-1)], but returned to baseline with continued weight gain. Return of FVR to baseline occurred between weeks 2 and 3 of overfeeding in the DNX limb, but did not return to baseline until week 6 in the innervated limb. These changes were not correlated with plasma insulin levels. DISCUSSION: These data suggest that vascular resistance may be normal in the obese, but increases in vascular resistance occur early with weight gain (before changes in arterial pressure). This initial increase in vascular resistance could initiate the series of events leading to obesity-associated hypertension. Additionally, changing vascular resistance during weight gain may be influenced by sympathetic activity, because DNX limb FVR returned to baseline approximately 3 weeks earlier than the innervated limb.

Composition of dietary fat affects blood pressure and insulin responses to dietary obesity in the dog.

Cardiovascular and metabolic parameters were evaluated in 15 female spayed dogs before and after they became obese on either a saturated fat (LD, lard, n=8) or unsaturated fat (CO, corn oil, n=7) diet. Body weight and body fat increased significantly in both groups, although no differences occurred between diet groups. Dogs receiving the LD diet exhibited a greater increase in mean arterial pressure than those receiving the CO diet (p<0.01; 15.9 +/- 2.1 vs. 9.8 +/- 3.3 mm Hg increase). The CO diet stimulated a greater increase in heart rate than the LD diet (p<0.05; 32.8 +/- 7.8 vs. 14.1 +/- 5.8 bpm increase). Ganglionic blockade with chlorisondamine caused an increase in HR in both lean groups and in the obese CO group, but not the obese LD group, consistent with a decrease in parasympathetic tone to the heart in the dogs overfed saturated fat. Obesity enhanced the heart rate response to beta-adrenergic stimulation by isoproterenol in the LD, but not CO group. The LD diet increased circulating insulin and decreased insulin sensitivity, whereas the CO diet had no effect on either parameter. These findings suggest that the composition of dietary fat can modulate the autonomic and metabolic adaptations induced by dietary obesity.

Differential metabolic effects of energy restriction in dogs using diets varying in fat and fiber content.

The role of dietary fat and fiber in energy restriction for the management of obesity was examined. Twelve male castrated dogs were energy restricted for 7 weeks by feeding 60% of their calculated maintenance energy requirements (MER = 1500 kcal/m2/d) for ideal body weight. Six dogs were restricted on a high-fat (35.4 kcal% from fat), low-fiber (2.9% dry matter basis [DMB]) diet while the other six dogs were restricted on a low-fat (24.5 kcal% from fat), high-fiber (27% DMB) diet. Compared with the high-fat, low-fiber diet, energy restriction on the low-fat, high-fiber diet resulted in significantly greater decreases in body fat (1472 +/- 166 vs. 853 +/- 176 g; p < 0.05) and total serum cholesterol concentrations (108.7 +/- 11.3 vs. 51.5 +/- 13.9 mg/dL; p < 0.005). Reductions in body weight (2.86 +/- 0.3 vs. 2.14 +/- 0.3 kg; p < 0.09), and mean arterial blood pressure (17.4 +/- 6.1 vs. 6.7 +/- 2.9 mmHg; p < 0.12) were also greater on the low-fat diet; however, these diet effects did not reach statistical significance. These data suggest that the fat and fiber content of the diet during energy restriction are important factors in the management of obesity.

Autonomic control of blood pressure and heart rate in obese hypertensive dogs.

Autonomic control of cardiovascular function was evaluated in nine dogs before and after a high-fat overfeeding regimen. Body weight increased significantly (from 19.8 +/- 0.9 to 29.5 +/- 2.1 kg; P < 0.01) with overfeeding. Mean arterial pressure (MAP) increased from 94.6 +/- 2.1 to 105.5 +/- 3.7 mmHg (P < 0.05), and heart rate (HR) increased from 94.8 +/- 3.5 to 112.3 +/- 5.6 beats/min (P < 0.01). After ganglionic blockade with chlorisondamine, dose response of MAP and HR to methoxamine (alpha-agonist) or isoproterenol (beta-agonist) was evaluated. Peak MAP response to methoxamine was blunted in obese dogs. HR response to isoproterenol was not different between lean and obese dogs. Atropine in the presence of propranolol increased HR from 80.8 +/- 7 to 202.8 +/- 8.9 beats/min in lean dogs and from 113.8 +/- 12.1 to 131.7 +/- 18.2 in obese dogs. These data suggest the increase in HR observed in obese dogs may be due to a decrease in parasympathetic inhibition rather than an increase in sympathetic stimulation. The blunted response to methoxamine in obese hypertensive dogs suggests that the sympathetic control of peripheral vascular resistance is altered in obesity.

Effect of sucralfate on healing of subclinical gastric ulcers in foals.

The effect of sucralfate on healing of subclinical gastric ulcers and gastric inflammation was investigated in twelve 6- to 7-month-old foals. Foals with endoscopically evident gastric lesions on day 0 were assigned to 1 of 2 groups, on the basis of mucosal inflammation and number and severity of ulcers, to create groups of foals with approximately equal severity of lesions. None of these foals had clinical signs of gastroduodenal ulcer disease. Groups were assigned to receive sucralfate (22.0 mg/kg of body weight) or corn syrup for 14 days, PO, every 8 hours. On day 15, gastroscopic examinations revealed that sucralfate did not promote greater healing than did the corn syrup.

Comparison of adverse effects of phenylbutazone, flunixin meglumine, and ketoprofen in horses.

The relative toxicity of phenylbutazone, flunixin meglumine, and ketoprofen was studied in healthy adult horses. Sixteen horses were randomly assigned to receive 10 ml of physiologic saline solution, or ketoprofen (2.2 mg/kg of body weight), flunixin meglumine (1.1 mg/kg), or phenylbutazone (4.4 mg/kg) IV, every 8 hours, for 12 days. Results of CBC, serum biochemical analyses, and fecal occult blood tests were monitored. On day 13, all horses were euthanatized and complete necropsy examinations were performed. Mean CBC values remained within normal limits for all groups. Phenylbutazone-treated horses had a significant (P < 0.05) decrease in serum total protein and albumin concentrations. Mean values of all other serum biochemical assays were not different from those of the saline-treated group. Results of all fecal occult blood tests were negative. At necropsy, the glandular portion of the stomach was the area of the gastrointestinal tract most severely affected by phenylbutazone, flunixin meglumine, and ketoprofen. In the phenylbutazone-treated group, but not in the other groups, edema of the small intestine and erosions and ulcers of the large colon were observed. None of the horses treated with saline solution had lesions in the glandular portion of the stomach or in the intestine. Four horses (1/5 and 3/3 in the flunixin- and phenylbutazone-treated groups, respectively) developed renal crest necrosis. Horses in the saline- and ketoprofen-treated groups did not develop renal lesions.(ABSTRACT TRUNCATED AT 250 WORDS)