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Angiotensin II receptor subtypes regulation and affinity changes in treated IDDM rat hearts
Author(s) -
Bikhazi Anwar B.,
Maharsy Wael M,
Bitar Khalil M,
ZWAINY DARINE S,
Issa Nahla G.
Publication year - 2006
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.20.5.a1195-a
Subject(s) - losartan , medicine , endocrinology , angiotensin ii receptor type 1 , angiotensin ii , receptor , insulin , diabetes mellitus , chemistry , angiotensin receptor
Study focused on regulation and affinity of angiotensin II to its AT1‐Rs/AT2‐Rs at coronary endothelium (CE) and cardiomyocyte (CM) in normal and STZ‐induced IDDM rats treated with insulin and/or losartan. Six groups: Normal (N), normal with losartan (NL), diabetic (D), diabetic with insulin (DI), diabetic with losartan (DL), and diabetic co‐treated with insulin and losartan (DIL). First‐order Bessel function was employed to estimate Ang II binding affinity (ô = 1/k‐n) to its receptor subtypes on CE and CM using heart perfusion with [I125]‐Ang II by dividing each group into two subgroups: CHAPS‐untreated and treated. Results showed that diabetes decreased ô value on CE and increased it on CM compared to the normal. The ô value in normal rat hearts treated with Losartan on CE and CM was unchanged. Diabetics treated with Losartan, ô value increased thus was not restored to the normal value on CE, however was normalized on CM. Insulin treatment restored ô to normal on both CE and CM. The ô was normalized with insulin and losartan co‐administration. Western blotting revealed increase in AT1‐Rs density in all groups except in DIL, where it was normal. Increase in AT2‐Rs density was observed in NL, minor increase in D, DI, and DL, and normal in DIL groups. In conclusion treatment of IDDM rats with both insulin and selective AT1‐Rs blocker diminishes the negative myocardial effects related to Ang II receptors regulation and affinities.