Type 2 bradykinin-receptor antagonism does not modify kinin or angiotensin peptide levels.
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.
Campbell
D J
DJ
St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia. J.Campbell@medicine.unimelb.edu.au
Kladis
A
A
Briscoe
T A
TA
Zhuo
J
J
D000804:Angiotensin II / Q000032:analysis* / Q000097:blood; D000808:Angiotensinogen / Q000097:blood; D000818:Animals; D001011:Aorta / Q000737:chemistry; D001345:Autoradiography; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D003627:Data Interpretation, Statistical; D005246:Feedback; D005470:Fluorometry; D066298:In Vitro Techniques; D007668:Kidney / Q000737:chemistry; D007705:Kinins / Q000032:analysis / Q000097:blood / Q000502:physiology*; D008168:Lung / Q000737:chemistry; D008297:Male; D009206:Myocardium / Q000737:chemistry; D015260:Neprilysin / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018002:Receptors, Bradykinin / Q000502:physiology*; D012083:Renin / Q000097:blood; D013997:Time Factors
D065168:Bradykinin Receptor Antagonists; D007705:Kinins; D018002:Receptors, Bradykinin; D000808:Angiotensinogen; D000804:Angiotensin II; C065679:icatibant; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D015260:Neprilysin; D001920:Bradykinin