Enhanced expression of tissue factor (TF) is associated with the occurrence of coronary disease, strokes and arterial thrombosis. We demonstrated previously that adenosine inhibits TF expression in human umbilical vein endothelial cells (HUVECs) stimulated with inflammatory mediators. In the present study, we evaluated the mechanism of adenosine-induced inhibition of TF expression in HUVECs. The adenosine inhibitory activity on thrombin-induced TF expression in HUVECs was potentiated by the NO precursor, l -arginine, but it was significantly suppressed by the NO scavenger, 2(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide, and by endothelial NO synthase inhibitors, N G -monomethyl- l -arginine and N G -nitro- l -arginine methyl ester, in a dose-dependent manner. The concentrations of nitrites, cGMP and cAMP in the culture medium of HUVECs treated with a mixture of thrombin and adenosine were significantly higher compared with the culture medium of HUVECs treated with thrombin alone. Northern blotting showed that thrombin decreases and adenosine increases the eNOS mRNA expression in HUVECs. A cAMP-dependent protein kinase inhibitor suppressed NO-mediated TF inhibition in a dose-dependent manner. Overall, these results suggest that adenosine inhibits thrombin-induced TF expression in endothelial cells by a NO-mediated mechanism, and that increased intracellular formation of cAMP is implicated in this inhibitory activity of NO.

1. The metabolic response of lean and obese women to caffeine was studied to see if caffeine could be used to demonstrate the subnormal thermogenesis in obesity previously shown after standard meals or intravenous infusions of noradrenaline. 2. The rise in resting metabolic rate with caffeine was similar in the lean and obese groups and β-adrenoceptor blockade did not reduce the increment in metabolic rate in either group. These responses did not, therefore, correspond with the other subnormal thermogenic responses of the constitutionally obese. 3. In a post-obese group, i.e. previously obese women who were now of normal weight, there was a reduced response of the resting metabolic rate to caffeine. 4. Monitoring plasma substrate concentrations showed that the change in oxygen uptake corresponded to changes in plasma free fatty acids, so that in adults the metabolic effects of caffeine seem to be mediated by increases in adipocyte lipolysis. This effect seems to be mainly independent of the adrenergic system.

1. The noradrenaline-induced accumulation of cyclic AMP is decreased in both the anterior and the posterior hypothalamus of hypertension-prone as compared with resistant rats, but is similar in the cortex. 2. The nonadrenaline-induced accumulation of cyclic AMP is decreased in the posterior hypothalamus as compared with the anterior hypothalamus of both strains. 3. The decreased sensitivity to phosphodiesterase inhibitor in the hypothalamus of hypertension-prone as compared with resistant rats suggests that strain differences in phosphodiesterase activity may exist. 4. Since differences in cyclic AMP were found in the hypothalamus and the medulla oblongata, regions involved in blood pressure control, but not in the cortex, they may be relevant to the diverse susceptibility to hypertension of hypertension-prone and resistant rats.

1. Intracellular concentrations of adenosine 3′: 5′-cyclic phosphate (cyclic AMP) and activities of adenylcyclase and phosphodiesterase were determined in oestrogen-pretreated rat uteri during exposure to different concentrations of angiotensin II. 2. No significant variations in cyclic AMP or in the enzyme activities were observed at concentrations of angiotensin inducing significant contractions. 3. It is concluded that in rat uterus, the process of excitation-contraction coupling triggered by angiotensin is not mediated by variations in intracellular levels of cyclic AMP.