Y. Sun et al., BRADYKININ RECEPTOR AND TISSUE ACE BINDING IN MYOCARDIAL FIBROSIS - RESPONSE TO CHRONIC ANGIOTENSIN-II OR ALDOSTERONE ADMINISTRATION IN RATS, Journal of Molecular and Cellular Cardiology, 27(2), 1995, pp. 813-822
High density angiotensin converting enzyme (ACE) binding is present in
the perivascular fibrosis involving intramyocardial coronary arteries
and the microscopic scarring of the myocardium that accompanies chron
ic elevations in circulating angiotensin II (AngII) and/or aldosterone
(ALDO). As a kininase II, ACE degrades bradykinin. Herein we sought t
o determine whether bradykinin (BK) receptor binding was associated wi
th ACE binding in each of these experimental models, BK receptor bindi
ng was localized and quantified by in vitro quantitative autoradiograp
hy, using [I-125-Tyr(8)]BK. In serial sections of the same heart hemat
oxylin and eosin (H&E) and picrosirius red (PSR) staining were utilize
d to address cardiac myocyte injury and fibrosis, respectively. Four e
xperimental groups were examined: unoperated, untreated, age/sex match
ed controls; age/sex matched uninephrectomized control rats receiving
a high sodium diet; animals that received AngII (9 mu g/h sc) for 2, 4
or 6 weeks; and uninephrectomized rats on a high sodium diet that rec
eived ALDO (0.75 mu g/h sc) for similar periods of time. We found: (a)
myocardial fibrosis, including perivascular fibrosis and microscopic
scarring, at week 2 of AngII, but not until week 4 or more of ALDO tre
atment; (b) low BK receptor binding in normal ventricles that was incr
eased in scars and markedly increased in perivascular fibrosis at week
2 of AngII and each increased further at week 4 and 6 of AngII; (c) l
ow BK receptor binding at week 2 and 4 weeks of ALDO treatment which b
ecame markedly increased at fibrous tissue sites at week 6. BK recepto
r and ACE binding were anatomically coincident and localized to each s
ite of fibrosis in both models. The co-location of BK receptor and ACE
binding in these models raises the prospect that fibrous tissue ACE m
ay utilize BK as substrate and BK, in turn, may play a role in fibrous
tissue formation.