© 1997 by European Society of Cardiology
Copyright © 1997, European Society of Cardiology
Fibrosis of atria and great vessels in response to angiotensin II or aldosterone infusion
Division of Cardiology, Department of Internal Medicine, University of Missouri Health Sciences Center, MA432 Medical Sciences Building, Columbia, MO 65212, USA
* Corresponding author. Tel.: +1 (573) 882-8580; fax: +1 (573) 884-4691.
Objective: Myocardial fibrosis, associated with increased expression of angiotensin converting enzyme (ACE) and bradykinin (BK) receptor binding at sites of tissue repair, accompanies chronic elevations in circulating angiotensin II (AngII) and/or aldosterone (ALDO) that simulate chronic cardiac failure. A role for increased ventricular wall stress, associated with arterial hypertension, that can accompany such neurohormonal activation when ventricular function is not compromised, has been held responsible for this structural remodeling. To address this proposition, we monitored morphology of right and left atria and pulmonary artery, where stress is not increased, and compared these structures with hypertensive aorta. Methods: Experimental groups included: (1) unoperated and untreated controls; (2) intact rats receiving AngII (9 µg/h) for 2 weeks and which causes arterial hypertension; (3) uninephrectomized control rats on a high sodium diet for 6 weeks; and (4) uninephrectomized rats receiving ALDO (0.75 µg/h) and a high sodium diet for 6 weeks and which results in gradual onset arterial hypertension. Fibrosis was identified by light microscopy in sections stained with collagen specific picrosirius red, while ACE, AngII and BK receptor binding were localized and quantitated by in vitro autoradiography using 125I-351A, 125I[Sar1,Ile8]AngII, and 125I[Tyr8]BK, respectively. AngII receptor subtype was defined by the presence of excess AT1 (losartan) or AT2 (PD123177) receptor antagonists, respectively. Results: With either AngII or ALDO administration, and compared to controls, we found: (1) microscopic scarring that replaced lost myocytes in both left and right atria; (2) an increase in adventitial collagen of both pulmonary artery and aorta (perivascular fibrosis); (3) markedly increased ACE binding at fibrous tissue sites in both atria and great vessels; (4) unchanged atrial and great vessel AT1 receptor binding; and (5) significantly increased BK receptor binding at sites of atrial and perivascular fibrosis. Conclusions: Thus, the appearance of atrial fibrosis and perivascular fibrosis of aorta and pulmonary artery, together with associated increase in ACE and BK receptor binding, in rats receiving AngII or ALDO suggests these responses are not related to altered ventricular wall stress or arterial hypertension, but rather to these effector hormones of the circulating renin–angiotensin–aldosterone system. Local BK, regulated by ACE found in fibrous tissue and BK receptor binding may play a role in structural remodeling of atria and great vessels in these rat models that simulate chronic cardiac failure.
KEYWORDS Fibrosis; Angiotensin receptor; Angiotensin converting enzyme; Autoradiography, in vitro; Bradykinin receptors
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