Ontogeny of endothelin receptors in the brain, heart, and kidneys of neonatal rats.

BACKGROUND: Endothelin (ET) plays an important role in many physiological functions. It has been demonstrated that endogenous ET-1 concentration in the central nervous system (CNS) changes with age; however the ontogeny of ETA and ETB receptors in the brain, heart, and kidneys during postnatal development has not been studied. METHODS: Brains, hearts and kidneys of rats at postnatal days 1, 7, 14 and 28 were evaluated for the expression of ETA and ETB receptors via Western blot. ETB receptors within the developing brain were further accessed via immunofluorescence. RESULTS: The mean organ and body weights increased proportionally with advancing age demonstrating normal growth. The expression of ETA receptors in the brain, heart, and kidneys and ETB receptor expression in the heart and kidneys was similar in these rats at postnatal ages 1, 7, 14 and 28days. However, brain ETB receptor expression significantly (P<0.001) decreased by 72% on day 28 compared to the levels on postnatal day 1. Upon immunofluorescent analysis, the intensity of ETB staining in the cerebral cortex and subventricular zones of the developing rat brain decreased significantly from day 1 to day 7 (P<0.001) and from day 7 to day 14 (P<0.0001). There was no further decrease in ETB intensity noted in the cerebral cortex and subventricular zones between day 14 and day 28 of postnatal age. The intensity of ETB receptor staining within the cerebrovasculature, on the other hand, increased significantly (P<0.05) from days 1 and 7 to day 14. CONCLUSIONS: These results demonstrate that expression of ETA receptors does not change with postnatal development. On the other hand ETB receptors in the cerebral cortex and subventricular zones of the brain decrease with age, while ETB receptors in the cerebrovasculature increase with age, implicating ETB receptor involvement in the structural maturity and development of the CNS.

Influenza and atherosclerosis: vaccination for cardiovascular disease prevention.

In both animal and human studies, strong prothrombotic and pro-inflammatory effects have been observed after influenza infection. Influenza is an important trigger for acute coronary syndromes, and it has been shown that in the US it may cause up to 90,000 deaths per year simply by triggering fatal myocardial infarctions. Multiple case-control and cohort studies have shown that the influenza vaccine has a marked protective effect against cardiovascular events, decreasing the incidence of these events by 20 - 70% in the settings of primary and secondary prevention. Although influenza vaccination is an extremely cost-effective method of cardiovascular protection and is recommended for all patients with cardiac diseases, it is largely underused in these patients. Therefore, increased efforts should be directed towards educating physicians and patients about the benefits of influenza vaccination in patients with coronary heart disease.

Leukocyte count and coronary heart disease: implications for risk assessment.

Inflammation is a key feature of atherosclerosis and its clinical manifestations. The leukocyte count is a marker of inflammation that is widely available in clinical practice. This paper reviews the available epidemiologic evidence for a relationship between the leukocyte count and coronary heart disease (CHD). Numerous epidemiologic and clinical studies have shown leukocytosis to be an independent predictor of future cardiovascular events, both in healthy individuals free of CHD at baseline and in patients with stable angina, unstable angina, or a history of myocardial infarction. This relationship has been observed in prospective and retrospective cohort studies, as well as in case-control studies. It is strong, consistent, temporal, dose-dependent, and biologically plausible. The relationship persists after adjustment for multiple CHD risk factors, including smoking. Elevated differential cell counts, including eosinophil, neutrophil, and monocyte counts, also predict the future incidence of CHD. Leukocytosis affects CHD through multiple pathologic mechanisms that mediate inflammation, cause proteolytic and oxidative damage to the endothelial cells, plug the microvasculature, induce hypercoagulability, and promote infarct expansion. In summary, leukocytosis has been consistently shown to be an independent risk factor and prognostic indicator of future cardiovascular outcomes, regardless of disease status. The leukocyte count is inexpensive, reliable, easy to interpret, and ordered routinely in inpatient and outpatient settings. However, its diagnostic and prognostic utility in CHD is widely unappreciated. Further studies are needed to assess the true impact of leukocytosis on CHD, compare it with other inflammatory markers such as C-reactive protein and lipoprotein phospholipase A(2) levels, and promote its use in CHD prediction.

Influenza and cardiovascular disease: is there a causal relationship?

There is mounting evidence in support of a significant role for influenza infection in the development of atherosclerosis and the triggering of its complications. Here we review the biologic basis of this relationship, with special emphasis on the pro-inflammatory and pro-thrombotic effects of influenza infection. We also discuss the related epidemiologic findings and discuss in detail the possible causal relationship between influenza and cardiovascular disease. We appraise the relationship between influenza and coronary heart disease, on the basis of Bradford Hill's criteria of causality. We show that our proposed relationship meets the following criteria: strength of association, consistency, temporal sequence, coherence, biologic plausibility, experimental evidence, and analogy. Further studies are needed to assess whether it meets the criterion of biologic gradient. Specificity is not met, but meeting that criterion is of least importance in the study of multifactorial chronic diseases such as coronary heart disease. These criteria do not yield indisputable evidence for or against cause-and-effect, but they can help researchers appraise available evidence and determine the areas that need further research. The case for expanding the research on the effect of influenza on cardiovascular disease is a strong one, for most of Hill's criteria are met.