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Role of the renin-angiotensin system in neointima formation after injury in rabbits.
- Source :
-
Hypertension (Dallas, Tex. : 1979) [Hypertension] 1994 Dec; Vol. 24 (6), pp. 671-8. - Publication Year :
- 1994
-
Abstract
- We investigated the role of the renin-angiotensin system in neointima formation in a species in which converting enzyme inhibitors have been so far ineffective in suppressing abnormal vascular repair. The effects of converting enzyme inhibition by perindopril and selective blockade of angiotensin subtype 1 receptor by DuP 753 were assessed on neointima formation after balloon injury of rabbit carotid artery. Myointimal growth was measured by histomorphometric analysis. In rabbits treated 6 days before and for 14 days after injury, perindopril (2 mg/kg per day PO, n = 7) significantly reduced neointima formation (-51%, P < .01). DuP 753 (1 mg/d, n = 8) infused perivascularly for 14 days in the vicinity of injured carotid artery also markedly suppressed myointimal thickening (-60%, P < .01). To determine whether angiotensin subtype 2 receptor was implicated in this vascular response, we infused CGP 42112A, a specific subtype 2 receptor ligand, continuously for 14 days according to the same protocol of DuP 753 administration. CGP 42112A (1 mg/d) did not change the neointima-media ratio, indicating that angiotensin subtype 2 receptors were not involved in myointimal hyperplasia in rabbits. Thus in rabbits, the renin-angiotensin system plays a major role in neointima formation, and the protective effect of perindopril appears to be mediated mainly by inhibition of angiotensin II production, because blockade of the subtype 1 receptor reduced myointimal growth in a manner similar to that of converting enzyme inhibition and because intracarotid infusion of angiotensin II (500 ng/min) at the site of injury enhanced the vascular response (+39%, P < .05). Bradykinin (500 ng/min) administered in the same conditions as angiotensin II did not modify neointima formation.
- Subjects :
- Angiotensin II antagonists & inhibitors
Angiotensin II pharmacology
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors pharmacology
Animals
Biphenyl Compounds pharmacology
Blood Pressure drug effects
Bradykinin pharmacology
Heart Rate drug effects
Imidazoles pharmacology
Indoles pharmacology
Losartan
Male
Oligopeptides pharmacology
Perindopril
Rabbits
Receptors, Angiotensin classification
Receptors, Angiotensin physiology
Tetrazoles pharmacology
Tunica Intima pathology
Renin-Angiotensin System physiology
Tunica Intima injuries
Tunica Intima physiopathology
Wound Healing drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0194-911X
- Volume :
- 24
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Hypertension (Dallas, Tex. : 1979)
- Publication Type :
- Academic Journal
- Accession number :
- 7995623
- Full Text :
- https://doi.org/10.1161/01.hyp.24.6.671