TY - JOUR
T1 - Effects of perindopril on tissue angiotensin-converting enzyme activity demonstrated by quantitative in vitro autoradiography
AU - Sakaguchi, Keiji
AU - Jackson, Bruce
AU - Chai, Siew Yeen
AU - Mendelsohn, Frederick A.O.
AU - Johnston, Colin I.
PY - 1988/1/1
Y1 - 1988/1/1
N2 - Inhibition of plasma angiotensin II generation does not fully explain the chronic hypotensive effects of angiotensin-converting enzyme (ACE) inhibitors. Therefore, the pattern of tissue ACT. inhibition in rats was studied after oral administration of perindopril. a new ACE inhibitor. Tissue ACE was measured by quantitative in vitro autoradiography using [125I]-351 A as a radioligand and compared with plasma ACE and the pressor response to intravenous (i.v.) angiotensin I. Following oral perindopril (I mg/kg). plasma ACE activity was acutely reduced, but recovered over 24 h. The peak concentration of plasma perindoprilic acid, the active diacid of perindopril. occurred at 1 h. and the drug was undetectable by 24 h. The pressor response to i.v. angiotensin I was inhibited by 95% at 4 h and had not fully recovered by 24 h. Four hours after oral administration of perindopril. ACE was markedly inhibited in the proximal tubules of the kidney (24% control), lung parenchyma (10%), and aortic wall (18%) (p < 0.01). At 24 h. ACE in these tissues had only partially recovered (32-63%). ACE was also identified in vascular endothelium of organs, including the lung, kidney, and testis: In these sites, vascular ACE showed a pattern of inhibition similar to that of aortic ACE. In contrast, ACE in testicular seminiferous tubules was unaffected by perindopril. These results demonstrate a prolonged effect of ACE inhibitors on tissue ACE that may better explain the time course of these drugs than the changes in plasma ACE or plasma levels of the drug.
AB - Inhibition of plasma angiotensin II generation does not fully explain the chronic hypotensive effects of angiotensin-converting enzyme (ACE) inhibitors. Therefore, the pattern of tissue ACT. inhibition in rats was studied after oral administration of perindopril. a new ACE inhibitor. Tissue ACE was measured by quantitative in vitro autoradiography using [125I]-351 A as a radioligand and compared with plasma ACE and the pressor response to intravenous (i.v.) angiotensin I. Following oral perindopril (I mg/kg). plasma ACE activity was acutely reduced, but recovered over 24 h. The peak concentration of plasma perindoprilic acid, the active diacid of perindopril. occurred at 1 h. and the drug was undetectable by 24 h. The pressor response to i.v. angiotensin I was inhibited by 95% at 4 h and had not fully recovered by 24 h. Four hours after oral administration of perindopril. ACE was markedly inhibited in the proximal tubules of the kidney (24% control), lung parenchyma (10%), and aortic wall (18%) (p < 0.01). At 24 h. ACE in these tissues had only partially recovered (32-63%). ACE was also identified in vascular endothelium of organs, including the lung, kidney, and testis: In these sites, vascular ACE showed a pattern of inhibition similar to that of aortic ACE. In contrast, ACE in testicular seminiferous tubules was unaffected by perindopril. These results demonstrate a prolonged effect of ACE inhibitors on tissue ACE that may better explain the time course of these drugs than the changes in plasma ACE or plasma levels of the drug.
KW - ACE inhibitors
KW - Angiotensin system
KW - Blood pressure
KW - Hypertension
KW - Quantitative in vitro autoradiography
KW - Renin
UR - http://www.scopus.com/inward/record.url?scp=0023696916&partnerID=8YFLogxK
U2 - 10.1097/00005344-198812000-00013
DO - 10.1097/00005344-198812000-00013
M3 - Article
C2 - 2467090
AN - SCOPUS:0023696916
SN - 0160-2446
VL - 12
SP - 710
EP - 717
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 6
ER -