Objective: To determine whether decreased cardiac responsiveness to isoproterenol in obesity is associated with alterations in b-receptors and=or adenylyl cyclase activity. Animals and Design: After 12 weeks of control or ad libitum high-fat diets, left ventricular tissue from lean and obese female New Zealand white rabbits was assayed for b-receptor binding density (11 lean, 11 obese) and isoproterenol-stimulated adenylyl cyclase activity (eight lean, 10 obese). Measurements: Nonlinear least squares regression analysis was used to determine maximum density of b-receptors and receptor affinity for 125 I-iodocyanopindolol. Four-parameter logistic regression was used to determine minimum, maximum, slope and EC 50 for isoproterenol-stimulated adenylyl cyclase activity. Results: Obese rabbits had elevated resting blood pressure and heart rate, and higher ventricular weights. However, badrenoceptor density and affinity were not significantly different in lean and obese rabbits. Basal and maximum isoproterenolstimulated adenylyl cyclase activity did not differ between lean and obese rabbits. In addition, maximal stimulation in response to sodium flouride did not differ between lean and obese. EC 50 for isoproterenol-stimulated adenylyl cyclase activity did not differ between lean and obese rabbits. Conclusion: Obesity-related decreases in responsiveness of the isolated heart to isoproterenol are not associated with alterations in b-receptor density and affinity. In addition, adenylyl cyclase activity appeared unchanged in ventricular preparations from obese rabbits. Decreased responsiveness to isoproterenol in obesity may be due to defects downstream of adenylyl cyclase activation of cyclic AMP.

Restraint in a metal tube is a reproducible method of inducing gastric ulcers in rats. However, it may be impossible to compare results from animals of different body weight. To make this comparison possible, a theoretical relation was established between the size of the tube and the body weight of the animal. When using this relation a constant ulcer incidence is obtained in animals of varying weight. Alterations of this factor in this relation allows an increase or decrease in the degree of restraint and the ulcer ratio.

Rats bred in an animal house with a light and obscurity artificial cycle of 12/12 h at 25° C were restrained for 24 h in metal tubes at 4 different temperatures 19°, 22°, 25° and 28° C. The frequency of gastric lesions in each group was respectively of 100%; 67%; 17% and 25%. Thus, small fluctuations of the ambient temperature around the average have a dramatic influence on the ulcer ratio. The cold exposure increases the susceptibility. The temperature fluctuation must be an important factor in the seasonal variations of ulcer frequency in various experimental conditions. A strict control of the temperature must be obtained to get a reproducible incidence of restraint ulcer.

The radioactivity was measured after proteolysis and dialysis in the gastric mucosa of 100 rats killed 6 h after injection of 100 µC of carrier-free radiosulfate. Controls were paired to rats restrained respectively 6, 12, 18 or 24 h. The radiosulfate metabolism was always assessed in the last 6 h. Non-dialyzable radiosulfate, index of the synthetized sulfated macromolecules, is significantly decreased in the gastric mucosa of the restrained animals. The values vary between 54 and 77% of controls. A defect in radiosulfate incorporation during the first, pre-ulcerous period of restraint is thus demonstrated. This alteration is observed earlier than the lesions in gastric mucosa, indicating that the metabolic disturbance is a significant factor in ulcerogenesis.

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