Pulmonary kinin metabolism and conversion of angiotensin I in spontaneously hypertensive rats.
OBJECTIVE
To examine the metabolism of kinins and angiotensin I in the pulmonary circulation of spontaneously hypertensive rats (SHR) and normotensive Wistar rats (NWR).


METHODS
Bradykinin inactivation was estimated in vivo by comparison of the hypotensive effect of intra-arterial and intravenous injections, and in the in situ perfused lung by analysing the breakdown products using high-performance liquid chromatography.


RESULTS
In vivo pulmonary degradation of bradykinin, but not that of higher homologues of this peptide, was shown to be significantly greater in SHR. Angiotensin I converting activity was found to be increased in lungs of SHR. The recovery of bradykinin and homologues from perfused SHR lung was decreased relative to NWR. Des-(Phe-Arg) fragments of all kinin analogues were identified in the pulmonary perfusates. When bradykinin and des-Arg9-bradykinin were injected in the perfused lungs, the respective fragments 4-9 and 4-8 were also identified in the perfusates. When kininase II was inhibited with enalaprilat, the recovery of bradykinin increased from 10 to 43% in SHR and from 23 to 58% in NWR, whereas about 90% of the higher bradykinin homologues were recovered in both SHR and NWR. Aminopeptidase P and dipeptidylaminopeptidase IV, as measured by the recovery of fragment 4-9 under kininase II inhibition, accounted for about 40% of the total pulmonary kininase activity in the SHR lungs and 25% of that of the NWR lungs.


CONCLUSIONS
The results show that SHR have increased kininase and angiotensin converting activity compared with NWR, and that kinins as well as angiotensin may contribute to the pathogenesis of hypertension. Aminopeptidase P and dipeptidylaminopeptidase IV may contribute to the increased in vivo degradation of bradykinin observed in the SHR.
Department of Biophysics, Paulista School of Medicine, São Paulo, Brazil.
J B
JB
Pesquero
P
P
Boschcov
C J
CJ
Lindsey
A C
AC
Paiva
D000626:Aminopeptidases / Q000378:metabolism; D000803:Angiotensin I / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001920:Bradykinin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism; D008168:Lung / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D017208:Rats, Wistar / Q000378:metabolism*
D000803:Angiotensin I; D000626:Aminopeptidases; C022750:X-Pro aminopeptidase; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin