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Impact of Bradykinin B1 Receptor Blockade on Angiotensin II‐Induced Cardiac and Aortic Remodeling
Author(s) -
McCormick Brittney,
HuotMarchand JulieEmilie,
deBlois Denis,
Hale Taben
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1070.5
Subject(s) - medicine , angiotensin ii , bradykinin , aorta , endocrinology , muscle hypertrophy , blood pressure , receptor
Angiotensin II (AngII) is a growth factor known to induce vascular and cardiac hypertrophy and fibrosis. AngII has been shown to regulate bradykinin B1 receptor (B1R) expression in the heart and aorta and we have recently shown that concomitant B1R antagonism could prevent AngII‐induced cardiac fibrosis. The present study investigated the impact of AngII and bradykinin B1R antagonism on blood pressure and left ventricular (LV) and aortic hypertrophy. Male Sprague‐Dawley rats were treated for 4 weeks with vehicle or AngII (200 ng/kg per min) in the presence or absence of the B1R antagonist R‐954 (400 μg/kg per day). In addition, bromodeoxyuridine (BrdU) was infused to assess cellular proliferation. At sacrifice, mean arterial pressure (MAP) was assessed via carotid artery cannulation in anesthetized rats. The LV and aorta were weighed, and the aortic and cardiomyocyte cross sectional area (CSA) were measured. Additionally, LV DNA content was determined and aortic cellular proliferation was assessed via immunohistochemistry to measure BrdU incorporation. Relative to vehicle, AngII increased MAP (59%), aortic cell proliferation (144%), and aortic CSA (34%), ‐ effects that were not offset by B1R antagonism. However, B1R antagonism did attenuate the AngII‐induced increase in aortic mass. Similarly, AngII increased LV hypertrophy (35%) and total DNA content (44%) relative to control, both of which were prevented by concomitant B1R antagonism. Cardiomyocyte CSA was not different across treatment groups. This study reveals tissue‐specific effects of bradykinin B1R antagonism. Although AngII induced significant remodeling in both the heart and aorta, concomitant B1R blockade only prevented cell accumulation and remodeling in the LV. Future studies will investigate the mechanism underlying this effect to further elucidate the role of the bradykinin B1R and its interaction with AngII in remodeling heart and aorta. Support or Funding Information Canadian Male Sexual Health Council