Myocardial fibrosis and pathological hypertrophy in the rat with aorta-constricted hypertension

We used the inter-renal abdominal aorta constriction model to induce hypertension and cardiac hypertrophy in rats within seven days after surgery. Rapid induction of hypertension resulted from the activation of the renin-angiotensin system (RAS) due to renal ischemia. Microscopically, marked interstitial fibrosis with focal necrosis and diffuse perivascular fibrosis in the myocardium were observed. Myocardial fibrosis appears before myocyte necrosis and its severity is proportional to the duration of established hypertension and the magnitude of blood pressure. To distinguish the humoral factors from mechanical factors, aorta-constricted hypertensive rats were treated with oral captopril or hydralazine. Captopril treatment prevented the development of hypertension, myocardial hypertrophy and fibrosis. Hydralazine treatment, although it reduced the blood pressure, did not prevent myocardial hypertrophy or fibrosis. This study reveals a potentially important clinical aspect of captopril, an angiotensin-converting enzyme (ACE) inhibitor which blocks the formation of angiotensin II (ANG II) from ANG I, which relates to the beneficial effects on myocardial hypertrophy and fibrosis (ventricular remodeling) in hypertension. However, ACE has other substrates in addition to ANG I, including kinins (which are potent vasodilators); thus, the mechanism of ACE's action may be more complex than mere blockade of ANG II formation. To further distinguish the relative role of hemodynamic and humoral factors in promoting myocardial fibrosis, we used osmotic minipumps to chronically infuse a subpressor dose of ANG II that induced a marked fibrotic response in the rat heart which was similar to the fibrotic lesions seen in the myocardium of aorta-constricted hypertensive rats. Since these cardiac lesions appear in both left and right ventricles, due to the in-series alignment, with respect to the systemic circulation of the ventricles, the occurrence of myocardial fibrosis and hypertrophy provides further evidence that ANG II may directly stimulate myocardial fibroblast proliferation and myocardiocyte hypertrophy through its trophic effect.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Physiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

1992

Author dc:creator

• Chang, Kevin Chijeng

• Biology, Animal Physiology

Statement dc:rights

• Copyright 1992 Chang, Kevin Chijeng

Language dc:language

eng

Identifier

AAI9215785
(UMI)AAI9215785

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/20401