Differential roles of AT1 and AT2 receptor subtypes in vascular trophic and phenotypic changes in response to stimulation with angiotensin II.
The aim of this study was to investigate the roles of angiotensin II (Ang II) receptor subtypes 1 (AT1) and 2 (AT2) in producing vascular wall hypertrophy and qualitative changes in smooth muscle cell gene expression. Wistar rats were treated for 23 days with osmotic minipumps containing solvent and either Ang II (120 ng.kg-1.min-1) or PD123319 (30 mg.kg-1.d-1), an AT2 receptor antagonist. In addition, rats receiving solvent and either Ang II or PD123319 were given losartan, an AT1 receptor antagonist, in the drinking water (10 mg.kg-1.d-1). Vascular wall hypertrophy and smooth muscle phenotype were characterized by morphometric analysis combined with immunohistochemistry. Ang II-induced hypertension was associated with the development of medial hypertrophy of the aorta and coronary arteries accompanied by reversion of vascular smooth muscle cells (VSMCs) toward an immature phenotype, as shown by the expression of cellular fibronectin and nonmuscle myosin. Losartan treatment, which restored normal arterial pressure, prevented all these changes. PD123319 treatment, which had no effect on blood pressure, prevented only vascular hypertrophy, with no effect on VSMC phenotype. Administration of only losartan to normal rats reproduced the Ang II-induced vascular hypertrophy, with no effect on VSMC phenotype. Taken together, these results suggest that (1) the trophic effect of Ang II on VSMCs is mediated via AT2 receptor subtypes and (2) changes in VSMC phenotypes are triggered mainly through AT1 receptor subtypes.
Sabri
A
A
U127 INSERM, Université D. Diderot, Paris, France.
Levy
B I
BI
Poitevin
P
P
Caputo
L
L
Faggin
E
E
Marotte
F
F
Rappaport
L
L
Samuel
J L
JL
D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology* / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D006984:Hypertrophy; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000502:physiology; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000502:physiology*; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology
D011945:Receptors, Angiotensin; D000804:Angiotensin II