PMID- 9867067
OWN - NLM
STAT- MEDLINE
DCOM- 19990115
LR  - 20190725
IS  - 0026-0495 (Print)
IS  - 0026-0495 (Linking)
VI  - 47
IP  - 12 Suppl 1
DP  - 1998 Dec
TI  - Attenuation of diabetes-associated mesenteric vascular hypertrophy with 
      perindopril: morphological and molecular biological studies.
PG  - 24-7
AB  - Vascular disease is now the major cause of morbidity and mortality in the 
      diabetic population. Our group explored the vascular changes associated with 
      experimental diabetes and examined whether these changes can be ameliorated by 
      angiotensin-converting enzyme (ACE) inhibition. The ACE inhibitor perindopril 
      (PE) was administered to streptozotocin-induced diabetic rats for 24 weeks. At 
      death, mesenteric vessels were perfused in vivo followed by assessment of the 
      vascular architecture by quantitative histomorphometry. In a subgroup of animals, 
      RNA was extracted from the mesenteric vasculature for assessment of gene 
      expression of the prosclerotic cytokine, transforming growth factor beta 1 
      (TGFbeta1), and the matrix protein, type IV collagen. Diabetes was associated 
      with smooth muscle hypertrophy and extracellular matrix (ECM) accumulation. ECM 
      accumulation, particularly collagen deposition, was observed in the medial and 
      adventitial layers. ACE inhibition prevented mesenteric vascular hypertrophy 
      after 24 weeks of diabetes. In addition, overexpression of TGFbeta1 in the 
      vessels of diabetic animals was prevented by PE treatment. Similarly, type IV 
      collagen mRNA levels were increased in diabetic vessels, and this overexpression 
      was also prevented by PE therapy. In summary, ACE inhibition attenuates many of 
      the vascular changes observed in experimental diabetes and may have important 
      clinical implications as a vasoprotective agent in human diabetes.
FAU - Cooper, M E
AU  - Cooper ME
AD  - Department of Medicine, University of Melbourne, Austin & Repatriation Medical 
      Centre, Heidelberg, Victoria, Australia.
FAU - Cao, Z
AU  - Cao Z
FAU - Rumble, J R
AU  - Rumble JR
FAU - Jandeleit, K
AU  - Jandeleit K
FAU - Allen, T J
AU  - Allen TJ
FAU - Gilbert, R E
AU  - Gilbert RE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Indoles)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta)
RN  - Y5GMK36KGY (Perindopril)
SB  - IM
MH  - Angiotensin-Converting Enzyme Inhibitors/*therapeutic use
MH  - Animals
MH  - Blood Vessels/pathology
MH  - Diabetes Mellitus, Experimental/drug therapy/genetics/pathology
MH  - Diabetic Angiopathies/*drug therapy/genetics/*pathology
MH  - Hypertrophy
MH  - Indoles/*therapeutic use
MH  - Male
MH  - Perindopril
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Splanchnic Circulation/*drug effects
MH  - Transforming Growth Factor beta/genetics
EDAT- 1998/12/29 00:00
MHDA- 1998/12/29 00:01
CRDT- 1998/12/29 00:00
PHST- 1998/12/29 00:00 [pubmed]
PHST- 1998/12/29 00:01 [medline]
PHST- 1998/12/29 00:00 [entrez]
AID - S0026-0495(98)90367-5 [pii]
AID - 10.1016/s0026-0495(98)90367-5 [doi]
PST - ppublish
SO  - Metabolism. 1998 Dec;47(12 Suppl 1):24-7. doi: 10.1016/s0026-0495(98)90367-5.