Des-aspartate-angiotensin I and angiotensin AT 1 receptors in rat cardiac ventricles

Abstract

The binding of 125I-[Sar 1,Ile 8]angiotensin II and 125I-angiotensin II to ventricular membranes of rat heart was studied. Displacement of bound 125I-[Sar 1,Ile 8]angiotensin II by its cold equivalents, angiotensin I, angiotensin II, angiotensin III, des-aspartate-angiotensin I, losartan, PD123319 and CGP42112B supports the presence of the AT 1 and the near absence of the AT 2 angiotensin receptor in adult rat ventricle. The presence of binding sites for des-aspartate-angiotensin I could account for its reported cardioprotective actions. Binding of 125I-angiotensin II but not that of 125I-[Sar 1,Ile 8]angiotensin II was partially displaced by GppNHp suggesting that a portion of the receptor population was in the active state with dissociated G-protein. Saturation experiments carried out in the absence and presence of 1 mM GppNHp showed similar magnitude of decrease in the number of receptors (Bmax from 26.2 ± 1.3 to 15.7 ± 1.1 fmol/mg protein) in [ 125I]-angiotensin II binding. However, the guanine nucleotide had no effect on the binding of 125I-[Sar 1,Ile 8]angiotensin II as has also been reported elsewhere, and may suggest that Sar 1-Ile 8-angiotensin II, being a partial agonist, binds to both the G-protein coupled and uncoupled states of the angiotensin receptors. The present study demonstrates that des-aspartate-angiotensin I binds to angiotensin receptors in the heart, and provides further evidence for its involvement in the pathophysiology of the organ.