The effect of weight reduction on levels of upright plasma norepinephrine (NE) and epinephrine (E) was studied in 20 obese patients maintained on a hypocaloric protein diet. Subjects were divided into 2 groups on either a constant 120 (N=13) or 40 (N=7) mmole sodium intake. Initial upright NE levels were higher (P < 0.001) in obese subjects (610 \ m=+-\ 52 pg/ml) than in non-obese controls (325 \m=+-\25 pg/ml). Initial NE in obese subjects correlated (r=0.6, P < 0.01) with mean arterial pressure. Weight loss in both sodium intake groups was accompanied by a progressive decline in upright NE and by 8 weeks levels were decreased in all study subjects by a mean of 42 per cent (P < 0.01) from baseline. Reductions in upright E from baseline were not as pronounced but were significant (P < 0.05) at 8 weeks on both sodium intakes. We have previously shown that mean arterial pressure and PRA decrease significantly in obese subjects during supplemented fasting independent of sodium intake. In the present study reductions in body weight correlated (r=58, P < 0.05) with both the fall in NE levels at 8 weeks (r=0.5, P < 0.05) and with reduction in upright PRA (r=0.49, P < 0.05) at weeks 4 to 8. Changes in upright E did not correlate with weight and blood pressure reductions. We conclude that reduction in caloric intake in obese patients is accompanied by significant reductions in upright NE and E that may contribute to the decline in resting blood pressure. The decrease in upright PRA with weight loss could result from depression in sympathetic nervous system activity.

Three parameters of coagulability--thrombin generation time (TGT), antithrombin III (AT III), and activated partial thromboplastin time (ATPP)--and two parameters of diabetic control--serial measurements of fasting serum glucose (FG) and hemoglobin A1(HbA1)--were used to study the relationship between diabetic control and hypercoagulability. Four groups of females were studied consisting of 10 young normal, 10 young insulin-dependent diabetic, 10 pregnant nondiabetic, and 8 first-trimester, insulin-dependent, pregnant diabetic subjects. Fasting serum glucose values and HbA1 were higher (P < 0.005) in nonpregnant diabetic subjects (193.1 +/- 29.1 mg/dl, 12.9 +/- 1.1%) and pregnant diabetic subjects (111.0 +/- 13.6 mg/dl, 8.2 +/- 1.7%) than in controls (64.8 +/- 4.4 mg/dl, 5.9 +/- 0.1%) and the nondiabetic pregnant females (71.6 +/- 3.8 mg/dl, 6.1 +/- 0.2%). Young diabetic females, pregnant females, and pregnant diabetic subjects had a shorter (P < 0.01) TGT than did the controls. AT III was greater (P < 0.01) for controls (99.7 +/- 2.7%) than for pregnant nondiabetic (83.2 +/- 3.8%), diabetic (79.5 +/- 2.5%), and pregnant diabetic subjects (76.2 +/- 4.4%). There was a positive correlation (r = 0.88, P < 0.005) between HbA1 and FG in the 10 young diabetic and in the 8 pregnant diabetic subjects (r = 0.74, P < 0.05). In the 10 diabetic females there was a negative correlation between AT III and FG (r = -0.76, P < 0.01) and between AT III and HbA1 (r = -0.79, P < 0.01). Thus, AT III is depressed in both diabetes and pregnancy, with pregnant diabetic subjects displaying the lowest AT III levels. Our observation that depression of AT III levels in young diabetic females was closely correlated with elevations of fasting serum glucose and HbA1 suggests that strict diabetic control may help prevent hypercoagulability in diabetes.

Adenylate cyclase activity was determined by enzymatic conversion of [32P]ATP to [32P]cAMP using peripheral lymphocytes freshly isolated from human subjects. The lymphocyte enzyme was stimulated by the potent fl-adrenergic catecholamine agonist isoproterenol and by the nonhydrolyzable GTP-analog Gpp[NH]p.' The two activators had a synergistic effect, and agonistdependent enzyme activity followed simple Michaelis-Menten kinetics with respect to isoproterenol in the presence but not in the absence of Gpp[NH]p. Cyclic AMP production by intact lymphocytes, determined by protein binding assay, also followed simple Michaelis-Menten kinetics with respect to isoproterenol. Ke of isoproterenol was the same in intact cells and the broken cell assay in the presence of Gpp[NH]p, suggesting the indispensable role the GTPbinding coupling factors play in the intact lymphocyte. In 31 human subjects between the age of 21 and 103, adenylate cyclase activity in the presence of isoproterenol, Gpp[NH]p, or isoproterenol in the presence of Gpp[NH]p decreased with the increasing age of the subject. The sensitivity of the enzyme to stimulation by isoproterenol, defined as the Km and determined in the presence of Gpp[NH]p, was the same in lymphocytes from young (<45 years) or elderly (>75 years) subjects. These results suggest a deficiency in the lymphocyte adenylate cyclase system distal to the fl-adrenergic catecholamine receptor could account for deterioration of CAMPmediated components of the immune response which occur with age. 475

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