Adrenaline suppression of the macrophage nitric oxide response to lipopolysaccharide is associated with differential regulation of tumour necrosis factor-alpha and interleukin-10.

Adrenaline is a catecholamine hormone secreted by the adrenal medulla in response to acute stress. Previous studies have shown that adrenaline suppresses the nitric oxide (NO) response of murine macrophages (M phi s) stimulated in vitro with lipopolysaccharide (LPS). We have now extended these studies to examine the effects of adrenaline on the production of tumour necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10). Our results showed that NO, TNF-alpha and IL-10 were concurrently produced following in vitro LPS (10 micrograms/ml) stimulation of murine peritoneal M phi s. Adrenaline suppressed both NO and TNF-alpha with concomitant up-regulation of the IL-10 response above that seen with LPS alone. In this in vitro model of LPS stimulation we demonstrated that TNF-alpha was required for NO production, as the TNF-alpha neutralizing monoclonal antibody, TN3.19.12, abolished the response; in contrast, IL-10 suppressed NO. In order to determine any functional consequence of adrenaline-mediated IL-10 augmentation on NO production, M phi s were stimulated with LPS and specific neutralizing anti-IL-10 antibodies were added to the cultures. The LPS NO response was suppressed to 43% of the control value by adrenaline (10(-8) M) and an irrelevant control antibody had no effect on the adrenaline-mediated inhibition of NO, but anti-IL-10 treatment restored the NO response to levels similar to those observed with LPS alone. Furthermore, we demonstrated that exogenous TNF-alpha, at a dose range of 1.9-50 ng per ml, also restored the nitrite response to LPS in the presence of adrenaline. Together, the observations that neutralization of IL-10 and addition of TNF-alpha abrogate adrenaline's inhibition of NO, suggest that this hormone suppresses NO partly through up-regulation of IL-10 which, in turn, may suppress TNF-alpha that is required for NO production. Finally, we also observed that the M phi-activating cytokine, interferon-gamma (IFN-gamma), attenuated the inhibitory effect of adrenaline on the LPS NO response.

Adrenaline inhibits macrophage nitric oxide production through beta1 and beta2 adrenergic receptors.

This study was conducted to investigate the role of the acute stress hormone adrenaline on macrophage nitric oxide (NO) production. Murine peritoneal macrophages were stimulated in vitro with lipopolysaccharide (LPS) in the absence or presence of adrenaline. Adrenaline inhibited the LPS-induced nitrite response in a dose-dependent manner. The suppressive effect of adrenaline on NO production was mediated via beta1 and beta2 adrenergic receptors since isoprenaline (a non-selective beta1 and beta2 agonist), dobutamine and salbutamol (selective beta1 and beta2 agonists, respectively) had similar effects on the NO response. In addition, the inhibitory effect of adrenaline on NO was abrogated by both propranolol (a non-specific beta blocker) and atenolol (a specific beta1 inhibitor). In contrast to beta receptor activation, the alpha adrenergic agonist phenylephrine had no effect on the LPS NO response, and furthermore, phentolamine (an alpha receptor antagonist) did not ameliorate adrenaline's inhibitory action.

Effect of variation in environmental temperature on blood pressure: is it important?

OBJECTIVES: To study the effect of variation in environmental temperature on blood pressure and pulse. DESIGN: Repeated blood pressure and pulse measurements in volunteers on two days when environmental temperatures differed by 10 degrees C. SETTING: Part of an ongoing community based study. SUBJECTS: 25 Black subjects (23 males and two females) volunteered from a population cohort participating in an ongoing longitudinal study examining cardiovascular risk factors in an urban African Black environment. MAIN OUTCOME MEASURE: Mean systolic and diastolic blood pressures and pulse rates. RESULTS: The systolic and diastolic blood pressures were significantly higher when recorded at 15 degrees C than at 25 degrees C, mean difference 32.2 +/- 4.2, p < 0.001 and 19.5 +/- 3.0 p < 0.001) for systolic and diastolic blood pressures respectively. The pulse rate per minute at 15 degrees C was significantly lower than at 25 degrees C (mean difference 11.1 +/- 3.2 p = 0.002). CONCLUSIONS: A decrease in environmental temperature by 10 degrees C appears to increase blood pressure. Awareness of this phenomenon is important, especially when surprisingly high blood pressures are observed during low ambient temperatures, to avoid over diagnosis of hypertension. This phenomenon, together with that already established of the white coat hypertension, may lead to the erroneous diagnosis of hypertension.

Factor VII, antithrombin III, leukocyte and platelet counts in a sample of black and white Zimbabwean blood donors.

Studies in Southern Africa have shown that whites have significantly greater morbidity and mortality from coronary heart disease than blacks. This study investigated the distribution of some haemostatic variables known or suspected to be correlated with greater risk for coronary heart disease in healthy black and white Zimbabwean men. Factor VII, antithrombin III, leukocyte and platelet counts were measured in 56 blacks and 29 whites aged between 20 and 50 years. We found significantly greater factor VII and leukocyte counts in the whites compared to the blacks. The other variables measured were similar in the two ethnic groups. These results suggest that the greater prevalence of coronary heart disease in whites is consistent with high levels of factor VII and white blood cell counts previously identified as risk factors for this condition.

Aspects of insulin resistance in urbanisation-related hypertension in Zimbabwe: a preliminary report.

Insulin resistance has been associated with essential hypertension, obesity and old age. Likewise high blood pressure has been observed to develop in some rural people who migrate to urban areas in developing countries like Zimbabwe. The pathogenesis of this urbanisation-related hypertension is still unknown. We therefore investigated aspects of insulin resistance in urbanisation-related hypertension in Zimbabwean blacks using oral glucose tolerance tests. Thirty normotensive subjects and 30 newly diagnosed hypertensive patients participated in this study. All subjects had blood pressures measured by random zero sphygmomanometry. Fasting blood samples were taken before a 75 g oral glucose load was given. Four other blood samples were subsequently collected at 30 minute intervals and determination of blood glucose and insulin levels was made. Fasting glucose (mmol/l) and fasting insulin (in microU/ml) levels were, respectively, 4.8 +/- 0.2 and 19 +/- 2 in hypertensive patients which were significantly higher than 4.0 +/- 0.2 and 13 +/- 1.6 in normotensive patients (P < 0.05). In addition the area under the insulin curve was significantly higher in hypertensive than in normotensive patients (P < 0.05). These findings suggest that insulin resistance may play a role in urbanisation-related hypertension.

African neutropaenia in Zimbabwe.

The distribution of total and differential leucocyte counts in a sample of Black and White Zimbabwean men living in the same environment was determined. White Zimbabweans had significantly higher total leucocyte counts than Black Zimbabweans and the difference was due to the significantly lower neutrophil counts in the Blacks. It was concluded that genetically determined "African neutropaenia" exists in Zimbabwe.

Plasma fibrinogen levels, leucocyte and platelet counts in male Zimbabwean hypertensives.

Plasma fibrinogen levels, leucocytes and platelets are among the many factors known to influence haemostasis. Impaired haemostatic processes in hypertension are thought to contribute to the other cardiovascular diseases seen in this condition. This study compares the level of plasma fibrinogen, and leucocyte and platelet counts between 17 male hypertensives and 24 male normotensives. The results for the hypertensives were: leucocyte count mean 5.45 x 10(9)/L, platelet count mean 234.7 x 10(9)/L, and plasma fibrinogen 4.13 g/L. The results for the normotensives were: leucocyte count mean 4.83 x 10(9)/L, platelet count mean 222.9 x 10(9)/L, and plasma fibrinogen 3.27 g/L. The hypertensives had higher plasma fibrinogen levels, and leucocyte and platelet counts compared to the normotensives, but this only reached statistical significance for the plasma fibrinogen levels (p < 0.025).

Ethnicity, haemostasis and cardiovascular disease: the evidence from Africa.

Disorders of both coagulation and fibrinolysis contribute to the development of cardiovascular diseases such as coronary artery disease, essential hypertension, ischaemic stroke and deep vein thrombosis. Different ethnic groups, in particular Blacks, Whites and Asians have different prevalences for the above diseases. Comparisons of these haemostatic processes in different ethnic groups have contributed greatly to the understanding of the pathogenesis of many of these diseases. Such studies, in particular those conducted in Africa, are reviewed below.

Relationship between bladder cancer incidence, Schistosoma haematobium infection, and geographical region in Zimbabwe.

Bladder cancer is common in Zimbabwe, possibly due to the high prevalence of Schistosoma haematobium infection in some areas. We undertook a correlational study based on retrospective medical record review to see whether the number of bladder cancers could be related to geographical region and prevalence of S. haematobium infection. We also determined patient demographic characteristics and tumour histology. Of 483 patients identified (1984-1987), 69% with available histology had squamous cell carcinomas. The remainder had transitional cell carcinomas. Patients with squamous cell carcinoma were younger than patients with transitional cell carcinomas (50% vs 20% under 50 years old, P less than 0.05) and had a sex ratio of one. There was a positive geographical relationship between S. haematobium prevalence and the incidence of squamous cell carcinoma of the bladder: provinces with high prevalence of S. haematobium had more bladder cancer cases with a predominance of squamous cell carcinoma (r = 0.87, P less than 0.01). These data support a casual relationship between S. haematobium infection and squamous cell carcinoma of the bladder.

Achalasia of the oesophagus in Bulawayo

Although oesophago-cardiomyotomy is the treatment of choice for achalasia 25 per cent of patients continue to have symptoms after surgery. This may be due to an inadequate myotomy; a myotomy which had healed; or the development of reflux oesophagitis

Relationship between bladder cancer incidence; schistosoma haematobium infection; and geographical region in Zimbabwe

Bladder cancer is common in Zimbabwe; possibly due to the high prevalence of Schistosoma haematobium infection in some areas. We undertook a correlational study based on retrospective medical record review to see whether the number of bladder cancers could be related to geographical region and prevalence of S. haematobium infection. We also determined patient demographic characteristics and tumour histology. Of 483 patients indentified (1984-1987); 69 with available histology had squamous cell carcinomas. The remainder had transitional cell carcinomas. Patients with squamous cell carcinoma were younger than patients with transitional cell carcinomas (50 vs 20 under 50 years old; P less than 0.05) and had a sex ration of one. [abstract terminated]