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(Hypertension. 1999;33:1233-1236.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Type 2 Bradykinin-Receptor Antagonism Does Not Modify Kinin or Angiotensin Peptide Levels

Duncan J. Campbell; Athena Kladis; Todd A. Briscoe; Jialong Zhuo

From St Vincent's Institute of Medical Research (D.J.C., A.K., T.A.B.), Fitzroy, Victoria; and Howard Florey Institute of Experimental Physiology and Medicine (J.Z.), Parkville, Victoria, Australia.

Correspondence to Dr D.J. Campbell, St Vincent's Institute of Medical Research, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia. E-mail J.Campbell{at}medicine.unimelb.edu.au

Abstract—Type 2 bradykinin (B₂)-receptor antagonists have been used to define the role of endogenous kinin peptides. However, interpretation of the effects of B₂-receptor antagonists has been limited by lack of information concerning the effects of these antagonists on endogenous kinin and angiotensin peptide levels. If kinin levels were subject to short-loop-feedback regulation mediated through B₂ receptors, then a reactive increase in kinin levels might blunt the effects of B₂-receptor antagonism and stimulate type 1 bradykinin receptors. Moreover, kinins have been implicated in the control of renin secretion. We investigated whether endogenous kinin levels are subject to short-loop-feedback regulation mediated by the B₂ receptor and whether endogenous kinins acting through the B₂ receptor influence plasma renin levels and circulating and tissue angiotensin peptide levels. The B₂-receptor antagonist icatibant (1 mg/kg) was administered to rats by intraperitoneal injection, and circulating and tissue levels of angiotensin and kinin peptides were measured after 4 hours. Icatibant produced 75% occupancy of B₂ receptors in the inner stripe of the renal medulla. Icatibant did not influence plasma levels of renin, angiotensinogen, angiotensin-converting enzyme, neutral endopeptidase, or circulating or tissue levels of angiotensin and bradykinin peptides. This study demonstrated that kinin levels are not subject to short-loop-feedback regulation mediated through B₂ receptors and that endogenous kinin levels acting through the B₂ receptor do not modulate the renin-angiotensin system.

Key Words: bradykinin • angiotensin • receptors, bradykinin • renin • angiotensinogen

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