A Clinically Relevant Functional Model of Type-2 Cardio-Renal Syndrome with Paraventricular Changes consequent to Chronic Ischaemic Heart Failure
Autor: | Emma Maria Hinemoa Besley, Scott Duncan George Smart, Jessica Renee Kelly, Ivan A. Sammut, Morgayn I. Read, Joanne C. Harrison, Yimin Yao |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty Angiotensin receptor Fractional excretion of sodium Heart Ventricles Cardiology Myocardial Infarction Myocardial Ischemia lcsh:Medicine Cardiorenal syndrome 030204 cardiovascular system & hematology Kidney Article Ventricular Function Left 03 medical and health sciences Ventricular Dysfunction Left 0302 clinical medicine Medical research Cardio-Renal Syndrome Internal medicine Medicine Animals Ventricular remodeling lcsh:Science Multidisciplinary Ventricular Remodeling business.industry lcsh:R Troponin I Hemodynamics medicine.disease Angiotensin II Rats Disease Models Animal Oxidative Stress 030104 developmental biology Renal pathology Rats Inbred Lew Heart failure lcsh:Q business Glomerular Filtration Rate Paraventricular Hypothalamic Nucleus |
Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020) |
ISSN: | 2045-2322 |
Popis: | Cardiorenal syndrome, de novo renal pathology arising secondary to cardiac insufficiency, is clinically recognised but poorly characterised. This study establishes and characterises a valid model representative of Type 2 cardiorenal syndrome. Extensive permanent left ventricular infarction, induced by ligation of the left anterior descending coronary artery in Lewis rats, was confirmed by plasma cardiac troponin I, histology and cardiac haemodynamics. Renal function and morphology was assessed 90-days post-ligation when heart failure had developed. The involvement of the paraventricular nucleus was investigated using markers of inflammation, apoptosis, reactive oxygen species and of angiotensin II involvement. An extensive left ventricular infarct was confirmed following coronary artery ligation, resulting in increased left ventricular weight and compromised left ventricular diastolic function and developed pressure. Glomerular filtration was significantly decreased, fractional excretion of sodium and caspase activities were increased and basement membrane thickening, indicating glomerulosclerosis, was evident. Interestingly, angiotensin II receptor I expression and reactive oxygen species levels in the hypothalamic paraventricular nucleus remained significantly increased at 90-days post-coronary artery ligation, suggesting that these hypothalamic changes may represent a novel, valuable pharmacological target. This model provides conclusive morphological, biochemical and functional evidence of renal injury consequent to heart failure, truly representative of Type-2 cardiorenal syndrome. |
Databáze: | OpenAIRE |
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