Interaction between atrial natriuretic peptide and the renin angiotensin aldosterone system. Endogenous antagonists

The biologic actions of the cardiac peptide hormone atrial natriuretic peptide (ANP) of vasorelaxation, diuresis and natriuresis, suppression of aldosterone, vasopressin release, and thirst are the opposite of those of the renin angiotensin system. This close relationship is further strengthened by the complementary localization of their receptors in the brain, adrenal gland, vasculature, and kidney. In many physiologic situations including postural changes, volume expansion, water immersion, high altitude, and lower body negative pressure, the plasma levels of ANP and angiotensin II change inversely. In congestive heart failure, renin and aldosterone levels may initially be suppressed by high levels of ANP. Similarly the low renin levels associated with increasing age and with elderly hypertensive patients, may be the result of the elevation of plasma ANP that occurs with aging. ANP may thus be the endogenous antagonist of the renin angiotensin aldosterone system. These two opposing systems allow fine-tuning of volume and pressure by the body

Type-2 airway inflammation in mild asthma patients with high blood eosinophils and high fractional exhaled nitric oxide.

Abstract Type‐2 (T2) inflammation is a characteristic feature of asthma. Biological therapies have been developed to target T2‐inflammation in asthma. IL‐13 is a key component of T2‐inflammation in asthma, driving mucus hypersecretion, IgE‐induction, and smooth muscle contraction. Early phase clinical trials for treatments that target T2‐inflammation require biomarkers to assess pharmacological effects. The aim of this study was to examine levels of IL‐13 inducible biomarkers in the airway epithelium of patients with mild asthma compared to healthy controls. Ten patients with mild asthma with high blood eosinophil and high fractional exhaled nitric oxide (FeNO) were recruited, and six healthy subjects. Blood eosinophil and FeNO reproducibility was assessed prior to bronchoscopy. Epithelial brushings were collected and assessed for IL‐13 inducible gene expression. Blood eosinophil and FeNO levels remained consistent in both patients with asthma and healthy subjects. Of the 11 genes assessed, expression levels of 15LOX1, POSTN, CLCA1, SERPINB2, CCL26, and NOS2 were significantly higher in patients with asthma compared to healthy controls. These six genes, present in patients with mild asthma with T2 inflammation, have the potential to be used in translational early phase asthma clinical trials of novel therapies as bronchial epithelial biomarkers

Type 2 inflammation in asthma — present in most, absent in many

Asthma is one of the most common chronic immunological diseases in humans, affecting people from childhood to old age. Progress in treating asthma has been relatively slow and treatment guidelines have mostly recommended empirical approaches on the basis of clinical measures of disease severity rather than on the basis of the underlying mechanisms of pathogenesis. An important molecular mechanism of asthma is type 2 inflammation, which occurs in many but not all patients. In this Opinion article, I explore the role of type 2 inflammation in asthma, including lessons learnt from clinical trials of inhibitors of type 2 inflammation. I consider how dichotomizing asthma according to levels of type 2 inflammation — into ‘T helper 2 (T(H)2)-high’ and ‘T(H)2-low’ subtypes (endotypes) — has shaped our thinking about the pathobiology of asthma and has generated new interest in understanding the mechanisms of disease that are independent of type 2 inflammation