Increased AT1 receptor binding density is associated with ACE binding and fibrillar collagen formation at sites of fibrous tissue formation following myocardial infarction in rats.
Does lisinopril alter angiotensin II receptor binding and fibrous tissue formation in a rat model of myocardial infarction?
In a rat model of myocardial infarction, increased AT1 receptor binding is associated with ACE binding and fibrosis, suggesting AT1 receptors mediate the fibrogenic response to tissue injury.
OBJECTIVE: The aim was to determine angiotensin II receptor binding and its relationship to angiotensin converting enzyme (ACE) binding and fibrous tissue formation in the rat heart. METHODS: A model of tissue repair (pericardiotomy and myocardial infarction with left coronary artery ligation) was used together with the following: quantitative in vitro autoradiography to determine angiotensin II receptor (125ISar1, Ile8AngII) and ACE (125I-351A) binding densities. Angiotensin II receptor subtype was determined using an AT1 receptor antagonist (DuP753, losartan) and an AT2 receptor antagonist (PD123177). Five groups were studied: age and sex matched controls receiving this operative procedure without subsequent myocardial infarction (sham operated); rats with coronary artery ligation and myocardial infarction; rats with coronary artery ligation and lisinopril (20 mg.kg-1.d-1 in drinking water); sham operated rats receiving lisinopril; and unoperated rats which served as controls to pericardiotomy. Hearts were collected from each group on postoperative day 3 and weeks 1, 2, 4, and 8. RESULTS: There was (1) low angiotensin receptor binding in normal myocardium; (2) markedly increased angiotensin II receptor binding at the site of left ventricular myocardial infarction and endocardial fibrosis of the interventricular septum at day 3 and weeks 1, 2, 4, and 8; (3) high angiotensin II receptor binding in the pericardial fibrosis that followed pericardiotomy, and in the fibrosis that appeared in response to suture insertion around the left coronary artery, in both infarcted and sham operated rats; (4) total displacement of normal and connective tissue angiotensin II receptor binding by DuP753, but not by PD123177; (5) ACE inhibition by lisinopril, but no change in angiotensin II receptor binding, at all sites of fibrosis; and (6) significant attenuation by lisinopril of collagen formation in the visceral pericardium of sham operated controls. CONCLUSIONS: In this model of tissue repair, increased AT1 receptor binding density is associated with ACE binding and fibrillar collagen formation that appears within sites of fibrous tissue formation, including myocardial infarction, endocardial fibrosis, foreign body (silk suture), and pericardiotomy. AT1 receptors may play a role in mediating the fibrogenic response to tissue injury in the rat heart.
Sun et al. (1994) studied Myocardial infarction and tissue repair. Lisinopril vs. Sham operated, unoperated controls, infarcted rats without lisinopril was evaluated on Angiotensin II receptor and ACE binding densities, and fibrous tissue formation. Increased AT1 receptor binding density is associated with ACE binding and fibrillar collagen formation at sites of fibrous tissue formation following myocardial infarction in rats.