Shimane Journal of Medical Science

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Shimane Journal of Medical Science 18 2
2000-12-01 発行

Failure of peripheral blood lymphocytes to be a surrogate marker of arterial tissue for tissue ace inhibition

Shimoura, Keiko
Kakizoe, Eiichi
Yokoyama, Satoshi
Wang, Dan-Qiao
Okunishi, Hideki
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Description
Previous studies in rats demonstrated that the inhibition of vascular tissue angiotensin-converting enzyme (ACE) was the determinant of antihypertensive action
of an ACE inhibitor, whereas plasma ACE inhibition was not. In patients, however, it is not practical to perform vascular tissue-biopsy merely to estimate drug effects. Therefore, the present study examined in rats practical to perform vascular tissue-biopsy merely to estimate drug effects. Therefore, the present study examined in rats whether or not peripheral blood lymphocytes (PBL) could be used as a surrogate marker for aortic tissue in respect of tissue ACE inhibition. Rats were treated daily for 6 days with one of the three ACE inhibitors (captopril, enalapril, and trandolapril) bearing different pharmacokinetic properties from each other. At a certain time after the final dosing, PBL and various tissues were harvested to measure ACE activity ex vivo. The present results confirmed the previous data for ACE inhibition in aorta and other tissues. Unexpectedly, however, ACE activity ex vivo of PBL was not reduced at all by any of the drug treatments, suggesting some drug-efflux mechanisms involved. In conclusion, PBL could not be used as the surrogate marker to estimate the vascular tissue ACE inhibition.
NCID
AA00841586