PMID- 11869839
OWN - NLM
STAT- MEDLINE
DCOM- 20020320
LR  - 20190708
IS  - 0735-1097 (Print)
IS  - 0735-1097 (Linking)
VI  - 39
IP  - 5
DP  - 2002 Mar 6
TI  - Gradual reactivation over time of vascular tissue angiotensin I to angiotensin II 
      conversion during chronic lisinopril therapy in chronic heart failure.
PG  - 767-75
AB  - OBJECTIVES: This study was designed to fully characterize vascular tissue 
      angiotensin I (AI)/angiotensin II (AII) conversion changes over time in vivo in 
      humans during chronic angiotensin-converting enzyme (ACE) inhibitor therapy. 
      BACKGROUND: Plasma AII does not remain fully suppressed during chronic ACE 
      inhibitor therapy. However, the plasma renin angiotensin system (RAS) might be 
      dissociated from the vascular tissue RAS. We therefore set out to characterize 
      the time course of vascular RAS reactivation during chronic ACE inhibitor 
      therapy. METHODS: Vascular AI/AII conversion was studied in patients with chronic 
      heart failure (CHF) taking chronic lisinopril therapy by the differential 
      infusion of AI and AII into the brachial artery. A cross-sectional study was done 
      to see whether there were differences in vascular AI/AII conversion according to 
      New York Heart Association (NYHA) class. A second longitudinal study followed 28 
      patients with NYHA I to II CHF serially over 18 months to see whether vascular 
      ACE inhibition was progressively lost with time despite ACE inhibitor therapy. A 
      third study examined whether increasing the dose of lisinopril affected 
      subsequent vascular ACE inhibition. RESULTS: In the cross-sectional study, 
      vascular AI-to-AII conversion was significantly reduced in NYHA class III 
      compared with class I/II (p < 0.05). In the longitudinal study, vascular ACE 
      inhibition was significantly reduced at 18 months as compared with baseline (p < 
      0.001), suggesting gradual reactivation of vascular ACE in CHF over time. In the 
      third study, tissue ACE inhibition could be restored by increasing the ACE 
      inhibitor dose. CONCLUSIONS: Vascular AI/AII conversion reactivates over time 
      during chronic ACE inhibitor therapy even if the CHF disease process is 
      clinically stable. It also occurs as the CHF disease process progresses. Even if 
      vascular AI/AII conversion has reactivated, it can be suppressed by increasing 
      the dose of the ACE inhibitor.
FAU - Farquharson, Colin A J
AU  - Farquharson CA
AD  - University Department of Clinical Pharmacology and Therapeutics, Ninewells 
      Hospital and Medical School, Dundee, United Kingdom.
FAU - Struthers, Allan D
AU  - Struthers AD
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 11128-99-7 (Angiotensin II)
RN  - 9041-90-1 (Angiotensin I)
RN  - E7199S1YWR (Lisinopril)
SB  - IM
CIN - J Am Coll Cardiol. 2002 Mar 6;39(5):776-9. PMID: 11869840
MH  - Aged
MH  - Angiotensin I/*metabolism
MH  - Angiotensin II/*biosynthesis
MH  - Angiotensin-Converting Enzyme Inhibitors/administration & dosage/*therapeutic use
MH  - Blood Vessels/*metabolism
MH  - Chronic Disease
MH  - Cross-Over Studies
MH  - Cross-Sectional Studies
MH  - Double-Blind Method
MH  - Female
MH  - Heart Failure/*drug therapy/*metabolism
MH  - Humans
MH  - Lisinopril/administration & dosage/*therapeutic use
MH  - Longitudinal Studies
MH  - Male
MH  - Middle Aged
MH  - Time Factors
EDAT- 2002/03/01 10:00
MHDA- 2002/03/21 10:01
CRDT- 2002/03/01 10:00
PHST- 2002/03/01 10:00 [pubmed]
PHST- 2002/03/21 10:01 [medline]
PHST- 2002/03/01 10:00 [entrez]
AID - S0735109702016893 [pii]
AID - 10.1016/s0735-1097(02)01689-3 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 2002 Mar 6;39(5):767-75. doi: 10.1016/s0735-1097(02)01689-3.