Histamine provides an original vista on cardiorenal syndrome

Abstract

Cardiac and renal dysfunction frequently go hand in hand in hospitalized patients, and epidemiological studies have suggested an inverse correlation between renal function and cardiovascular morbidity and mortality. This relationship exists regardless of what organ is first affected (1). It reflects upon a complex interplay between heart and kidneys, with dysfunction of one organ often impairing the function of the other. The causal association between chronic kidney disease (CKD) and cardiovascular risk was initially discussed by Bright in 1836. The notion of passive renal congestion arising from cardiac dysfunction was coined "rein cardiaque" by French pathologist Frédéric Justin Collet in 1903, while "cardiorenal syndrome" (CRS) was introduced in the 1940s to describe the bidirectional interactions between heart and kidneys (2). Kidney injury will stress both the heart and the circulatory system and cardiac dysfunction can, reciprocally, inflict injury on the kidney. Determinants of CRS include hemodynamic parameters such as central venous pressure, extracellular fluid volume, cardiac output, arterial pressure, pulmonary hypertension, and edema. Reduced cardiac performance ultimately limits blood perfusion of all organs including the kidneys and thereby contributes to renal injury. Altered tissue perfusion with disproportionate effects on the kidney leads to overactivation of both the sympathetic nervous and renin-angiotensin systems (RAS) reported in CRS. Inadequate renal extracellular fluid handling may have deleterious effects on the heart with an ensuing increase in volume preload and afterload and thus myocardial oxygen demand and vasoconstriction-including of coronary vessels-and an increase in inflammation, reactive oxygen species, and fibrosis (3). Clinical and epidemiological studies support a causal relationship between CKD, cardiovascular risk, and heart failure (4, 5). In patients with congestive heart failure, a moderate elevation in serum creatinine levels (e.g., by 26.5 μmol/L [0.3 mg/dL]) will significantly increase cardiovascular mortality (6). Thus, even subtle alterations in

Combination of sacubitril/valsartan and blockade of the PI3K pathway enhanced kidney protection in a mouse model of cardiorenal syndrome

“…Previous reports have indicated that ANS mice are classified as type 3 or 4 CRS because renal damage precedes cardiac damage. 25 , 36 , 37 In this study, ANS mice was associated with cardiac fibrosis, cardiac dysfunction, overt albuminuria, and kidney interstitial fibrosis. ARNI treatment prevented the increase in cardiac fibrosis and inflammation in mice with ANS, whereas valsartan did not.…”

Cardiorenal damages in mice at early phase after intervention induced by angiotensin II, nephrectomy, and salt intake

“…In the present study, we found that ANS mice exhibit structural abnormalities and impaired function of the kidneys prior to the decline in cardiac function. These suggested that ANS mice might be a model to elucidate the mechanisms for CRS causing transition from early to late-stage damages of cardiorenal tissues [ 30 ].…”

HPLC‐QTOF/MS‐based metabolomics to explore the molecular mechanisms of Yiqi Fumai Lyophilized Injection in heart failure mice

“…The low activity of CASD is more likely to cause taurine deficiency which eventually leads to heart failure accompanied by myocardial fibrosis [41, 42]. Histamine, the product from histidine metabolism, is synthesized via catalytic decarboxylation of histidine by histidine decarboxylase (HDC) [43]. The HDC‐knockout (HDC −/− ) mice exhibited poorer left ventricular function and more adverse cardiac remodeling, in addition, histamine inhibited heart fibroblast proliferation in vitro, which suggested that histamine could modulate myocardial fibrosis to offer the cardioprotective effect [44].…”