OBJECTIVE: To determine whether the renal growth associated with obesity is due to hypertrophy or hyperplasia. DESIGN: New Zealand white female rabbits were fed either standard rabbit chow (n 17) or chow foriti®ed with 10% corn oil plus 5% lard (n 18) for 12 ± 16 weeks. MEASUREMENTS: All rabbits were weighed, and intra-arterial blood pressures were successfully measured at the end of the study in 16 lean and 18 obese rabbits; percent water of entire kidneys (8 lean, 8 obese rabbits) and of de®ned regions of kidneys (8 lean, 10 obese rabbits) were obtained gravimetrically. Renal hemoglobin, protein and DNA was measured chemically (8 lean, 8 obese rabbits). RESULTS: Kidneys grew in size as the rabbits gained fat. In a series of 8 lean and 8 age-matched obese rabbits, weighing 3.7 AE 0.1 kg and 5.4 AE 0.4 kg (P`0.05), the kidneys were 20% larger in the obese rabbits: 15.0 AE 0.9 g vs 18.0 AE 2.5 g (P`0.05). Kidney protein was also 20% greater in the obese rabbit: 1.38 AE 0.06 gakidney vs 1.66 AE 0.06 gakidney (P`0.05). While total renal DNA was 16% greater in the obese: 18.2 AE 0.5 mgakidney vs 21.1 AE 0.6 mgakidney (P`0.05), no signi®cant difference existed when the DNA was expressed as mgamg protein.Fractional water content of the intact kidney declined with obesity: 78.7 AE 1.1% vs 76.0 AE 1.2% (P`0.05). Conversely, the hemoglobin content of the kidney at autopsy, an estimate of the unstressed vascular volume, increased with obesity: 55 AE 19 mgakidney vs 82 AE 25 mgakidney (P`0.05). By contrast, water content of renal parenchyma was constant: 80.8 AE 1.0% vs 80.9 AE 1.2% (cortex); 84.0 AE 0.8% vs 83.6% AE 2.0% (outer medulla); and 85.7 AE 0.8% vs 86.0 AE 2.1% (inner medulla). CONCLUSION: The renal growth associated with obesity was predominantly hyperplastic and was associated with a partial exclusion of¯uid from the renal sinus.

B-mode ultrasound was used to measure fat and muscle thicknesses on 30 subjects (17 men, 13 women, age = 20-37 yr) at 14 sites (triceps, biceps, forearm, chest [males only], subscapular, axilla, abdomen, suprailium, lumbar, quadriceps, suprapatellar, hamstrings, medial calf, and posterior calf) on two different days. Quadruplicate photographic images (trials) were printed from a single measurement at each site on each day. Two investigators each measured two of the images from each site. Each thickness was measured to the nearest 0.05 mm with a vernier caliper. Generalizability theory was used to determine the relative contribution of subjects, investigators, days, and trials to the total measurement variability. Subjects accounted for 84-96% of the variance in the muscle measurements and for 79-97% of the variance in the fat measurements. A subjects-by-day interaction accounted for 2-13% of the variance in muscle measurements and 2-12% of the variance in fat measurements. The contribution by investigators and trials to the variance was less than 1%. Generalizability coefficients (G) exceeding 0.92 were obtained for all sites for muscle measurements, while G for fat measurements exceeded 0.90 for all but the axilla site (G = 0.88). These results indicate that B-mode ultrasound is a highly reliable method for the measurement of both fat and muscle thicknesses in young males and females. © 1992 Wiley-Liss, Inc.

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.

OBJECTIVE: To investigate whether there is a defect in the post-b-receptor signaling pathway in isolated hearts of obese, hypertensive rabbits compared with their lean, normotensive counterparts. DESIGN: Female New Zealand white rabbits were fed a maintenance (n 5) or a 10% fat diet (n 6) for 12 weeks. MEASUREMENTS: After 12 weeks, rabbits were weighed and resting blood pressure and heart rate measured in the conscious animal using a central ear artery catheter. The isolated heart preparation was used to measure peak developed pressure, peak rate of pressure rise ( dPadt), and peak rate of pressure decline ( 7 dPadt) under control and 10 76 M forskolin-stimulated conditions. RESULTS: In response to forskolin, developed pressure increased 55% in lean rabbits, but only 18% in obese rabbits. Similarly, the increase in dPadt in response to forskolin was attenuated in obese rabbits ( 52%) compared with lean rabbits ( 121%). Relaxation ( 7 dPadt) in response to forskolin was also impaired, increasing 113% in lean rabbits but only 58% in obese rabbits. CONCLUSIONS: Since forskolin bypasses the b-receptor to directly stimulate adenylate cyclase, these results suggest that obesity-hypertension is associated with a defect in post-b-receptor signaling pathways.