Partial nephrectomy as a model for uremic cardiomyopathy in the mouse.

Abstract

Because of the plethora of genetic manipulations available in the mouse, we performed a partial nephrectomy in the mouse and examined whether the phenotypical features of uremic cardiomyopathy described in humans and rats were also present in the murine model. A 5/6 nephrectomy was performed using a combination of electrocautory to decrease renal mass on the left kidney and right surgical nephrectomy. This procedure produced substantial and persistent hypertension as well as increases in circulating concentrations of marinobufagenin. Invasive physiological measurements of cardiac function demonstrated that the 5/6 nephrectomy resulted in impairment of both active and passive left ventricular relaxation at 4 wk whereas tissue Doppler imaging detected changes in diastolic function after 6 wk. Morphologically, hearts demonstrated enlargement and progressive fibrosis, and biochemical measurements demonstrated downregulation of the sarcoplasmic reticulum calcium ATPase as well as increases in collagen-1, fibronectin, and vimentin expression. Our results suggest that partial nephrectomy in the mouse establishes a model of uremic cardiomyopathy which shares phenotypical features with the rat model as well as patients with chronic renal failure.

• Authors: David J Kennedy, Jihad Elkareh, Amjad Shidyak, Anna P Shapiro, Sleiman Smaili, Krishna Mutgi, Shalini Gupta, Jiang Tian, Eric Morgan, Samer Khouri, Christopher J Cooper, Sankaridrug M Periyasamy, Zijian Xie, Deepak Malhotra, Olga V Fedorova, Alexei Y Bagrov, Joseph I Shapiro
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 294 Issue 2 Pg. F450-4 (Feb 2008) ISSN: 1931-857X [Print] United States
• PMID: 18032546 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Bufanolides
• marinobufagenin
• src-Family Kinases
• Extracellular Signal-Regulated MAP Kinases
• Sarcoplasmic Reticulum Calcium-Transporting ATPases
• Atp2a2 protein, mouse
• Sodium-Potassium-Exchanging ATPase

Topics

• Animals
• Antihypertensive Agents (pharmacology)
• Blood Pressure (drug effects, physiology)
• Bufanolides (blood)
• Cardiomegaly (metabolism, pathology)
• Cardiomyopathies (etiology, metabolism, physiopathology)
• Disease Models, Animal
• Echocardiography, Doppler
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Fibrosis
• Heart (drug effects, physiopathology)
• Male
• Mice
• Mice, Inbred Strains
• Myocardium (metabolism, pathology)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Nephrectomy
• Renal Insufficiency (complications)
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (metabolism)
• Sodium-Potassium-Exchanging ATPase (metabolism)
• Stroke Volume (physiology)
• Ventricular Function, Left (physiology)
• src-Family Kinases (metabolism)