Exogenous cortisol raises blood pressure (BP) in humans and there is accumulating evidence of abnormalities of glucocorticoid activity in essential hypertension. In this study we tested the hypothesis that exogenous cortisol attenuates the cholinergic dilator response in the forearm circulation. Fourteen healthy normotensive men were studied. Using bilateral forearm venous plethysmography, we examined forearm blood flow responses to intra-arterial acetylcholine (ACh) and sodium nitroprusside (SNP) pre- and post-NG-monomethyl-L-arginine (LNMMA) after 2 or 5 days of oral cortisol or placebo in a randomized, double-blind crossover study. Exogenous cortisol increased supine systolic (P < .05) and standing systolic (P < .05) BP and produced expected metabolic changes and suppressed serum cortisol concentration (P < .001). Baseline forearm blood flow did not differ between placebo and cortisol treatments at 2 or 5 days. Cholinergic vasodilatation was impaired after cortisol administration, reaching statistical significance at 5 days (P < .05). Cortisol did not affect responses to SNP. NG-monomethyl-L-arginine inhibited cholinergic vasodilatation in placebo-treated groups but had no additional effect in the presence of cortisol. These results support our hypothesis and suggest that the mechanism of impaired cholinergic dilatation in glucocorticoid-treated subjects involves abnormalities of the endothelial nitric oxide system.

The effect of histamine and cimetidine on the growth of four human colon cancer cell lines was studied. Histamine significantly stimulated the uptake of tritiated thymidine in vitro in a dose dependent manner, to a maximum of 120% and 116% of controls for C170 and LIM2412, respectively. This effect was antagonised by cimetidine, but not diphenhydramine.

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Malnutrition and wasting are important determinants of morbidity and mortality in patients with chronic renal failure on dialysis. The aim of this study was to determine body composition and energy metabolism in patients with chronic renal insufficiency before dialysis. We compared 15 patients (9 women and 6 men) with chronic renal failure (creatinine, 1.5 to 4.2 mg/dL) with 15 normal subjects pair-matched for sex, age (renal failure versus normal, 71 +/- 3 years versus 64 +/- 3 years), height (1.61 +/- 0.02 m versus 1.64 +/- 0.02 m), and weight (64.5 +/- 2.7 kg versus 66.4 +/- 1.5 kg). Body composition was measured by dual-energy x-ray absorptiometry, and total body water was measured by bioelectrical impedance. Energy metabolism was determined by indirect calorimetry. The average glomerular filtration rate for the patients with chronic renal insufficiency was 23.9 +/- 2.6 mL/min/1.73 m2. Lean body mass (41.1 +/- 2.0 kg versus 44.5 +/- 2.2 kg; P = 0.003) and bone mineral content (2.35 +/- 0.11 kg versus 2.72 +/- 0.12 kg; P = 0.007) were significantly lower in chronic renal insufficiency; however, fat body mass was the same (19.9 +/- 2.1 kg versus 19.1 +/- 1.4 kg; P = 0.68). Total body water was similar in renal failure (33.4 +/- 1.5 L versus 34.4 +/- 1.3 L; P = 0.13). Basal energy expenditure was significantly lower in chronic renal insufficiency (1,085 +/- 50 kcal/24 hours versus 1,280 +/- 54 kcal/24 hours; P = 0.02), even after adjustment for the differences in lean body mass. Daily caloric intake indicated energy intake was similar in the patients with chronic renal insufficiency and the controls. Patients with a relatively modest degree of chronic renal insufficiency are characterized by reduced lean body mass, bone mineral content, and basal energy expenditure. The determinants of lean body mass in chronic renal insufficiency require further investigation.

1. The aim of the present study was to assess the role of the nitric oxide (NO) system in cortisol-induced hypertension in humans. 2. Plasma and urinary nitrate/nitrite concentrations and plasma concentrations of arginine and symmetric (SDMA) and asymmetric (ADMA) dimethyl arginine were measured in six subjects on a restricted nitrate diet who were treated with 80 mg/day cortisol and in subjects on an unrestricted nitrate diet who were treated with cortisol (80 mg/day, n = 6, or 200 mg/day, n = 10) for 5 days. 3. Cortisol significantly increased systolic and mean arterial pressure. Significant reductions in plasma nitrate/nitrite concentrations were observed in subjects on a restricted nitrate diet on days 3, 4 and 5 of cortisol treatment (to 11 +/- 1, 10 +/- 1, 11 +/- 1 pmol/L, respectively) compared with pretreatment (16 +/- 1 pmol/L; P < 0.01). There were no significant changes in plasma arginine, ADMA or SDMA concentrations. 4. Cortisol treatment significantly increased blood pressure and reduced plasma nitrate/nitrite concentrations. Reductions in plasma nitrate concentrations are not explained by changes in substrate availability or in endogenous nitric oxide synthase inhibitors. These data support a role for the NO system in cortisol-induced hypertension in humans.

Insulin resistance and hyperinsulinaemia are associated with hypertension although a causative relationship has not been established. The aim of this study was to determine whether a short term reduction in insulin sensitivity induced by nicotinic acid treatment (NA) would alter blood pressure. The study was a double-blind randomised placebo-controlled cross-over study. Seven healthy volunteers, three males and four females were randomised to placebo or NA 500 mg daily for 7 days then 1 g daily for a further 7 days. Hyperinsulinaemic euglycaemic clamp, indirect calorimetry, 24-h ambulatory blood pressure monitoring (ABPM) and forearm blood flow measurement (FABF) were performed at day 14 of each treatment phase. NA significantly reduced the glucose infusion rate required to maintain euglycaemia in all subjects (placebo vs NA; 31.5 ± 4.2 vs

Summary Histamine has recently been shown to be a growth factor for some gastric and colorectal cancer cells. Previous studies have shown that cimetidine blocks in vitro and in vivo histamine-stimulated growth and cAMP release from the human colonic cancer cell line, C170. In this study, ranitidine, another H2 receptor antagonist, did not affect either basal or histamine-stimulated in vitro proliferation of C170, and failed to prevent cAMP release in vitro. Ranitidine did not inhibit in vivo growth of C170 at a dose of 1, 10, 25, 50 or 100 mg kg-', in contrast to 50 mg kg -day-' cimetidine, which produced 39.3% inhibition of tumour volume (P<0.01) after 23 days' treatment. Ranitidine did not inhibit in vivo histamine-stimulated growth of C170 cells.LIM2412, another colonic cancer cell line, was significantly stimulated by both cimetidine and ranitidine in vivo. Ranitidine had no effect on in vitro cell proliferation.

To determine the hemodynamic and clinical consequences of an atherosclerotic obstructive lesion of the innominate artery on the cerebral circulation, 20 patients with an innominate artery lesion underwent neurologic examination and ultrasonic duplex scanning before and after right arm exercise. The patients were divided into two groups: Group 1, 12 patients with 40-80% stenosis and Group 2, eight patients with 80-100% stenosis. A significant difference between the groups was noted in both the hemodynamic and clinical manifestations. All 12 Group 1 patients compensated for the increased demand for blood of the right arm through the innominate artery itself, and only one showed symptoms of vertebrobasilar insufficiency associated with right arm exercise. In all eight Group 2 patients, compensation through the innominate artery failed; six (75%) showed symptoms of vertebrobasilar insufficiency after exercise. Dynamic duplex scanning is well suited to investigate stenotic lesions of the innominate artery, the effects of arm exercise on the development of cerebral symptoms, and the source of blood flow to the arm. Dynamic duplex scanning proved to be useful in selecting patients who may be candidates for direct arterial surgery. (Stroke 1988;19:958-962)