Angiotensin deficiency in mice leads to dilated cardiomyopathy.
To explore the role of angiotensin II, we assessed hemodynamics and cardiac function in angiotensinogen-deficient mice in comparison to wild-type animals. Left ventricular end-diastolic diameter and wall thickness were evaluated by echocardiography and systolic and diastolic left ventricular function by pressure-volume relations using a micro-conductance catheter. Compared to wild-type animals, the angiotensinogen-deficient mice were hypotensive and showed impaired systolic function. The hearts were dilated, demonstrated by echocardiography and by a right-ward shift of the pressure-volume loops, but end-diastolic pressure, isovolumic relaxation (tau) and diastolic stiffness were unchanged. Afterload, however, was reduced leading to maintained cardiac output. Although a blockade of the renin-angiotensin system via angiotensin converting enzyme inhibitors or angiotensin AT1 receptor antagonist is beneficial after cardiac failure, the absence of angiotensin peptides during the ontogenesis leads to dilated cardiomyopathy.
Walther
Thomas
T
Department Cardiology, Campus Benjamin Franklin, Charité Berlin, Hindenburgdamm, Germany. t.walther@erasmusmc.nl
Steendijk
Paul
P
Westermann
Dirk
D
Hohmann
Claudia
C
Schulze
Karsten
K
Heringer-Walther
Silvia
S
Schultheiss
Heinz-Peter
HP
Tschöpe
Carsten
C
D000804:Angiotensin II / Q000172:deficiency* / Q000235:genetics; D000808:Angiotensinogen / Q000172:deficiency / Q000235:genetics; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000209:etiology*; D004195:Disease Models, Animal; D004452:Echocardiography / Q000295:instrumentation / Q000379:methods; D006439:Hemodynamics / Q000502:physiology; D007022:Hypotension / Q000209:etiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009426:Netherlands; D011945:Receptors, Angiotensin / Q000502:physiology; D013318:Stroke Volume / Q000502:physiology; D016277:Ventricular Function, Left / Q000502:physiology
D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D000804:Angiotensin II