Chronic blockade of AT2-subtype receptors prevents the effect of angiotensin II on the rat vascular structure.
Angiotensin II (Ang II) is both a vasoactive and a potent growth-promoting factor for vascular smooth muscle cells. Little is known about the in vivo contribution of AT1 and AT2 receptor activation to the biological action of Ang II. Therefore, we investigated the effect of AT1 or AT2 subtype receptor chronic blockade by losartan or PD123319 on the vascular hypertrophy in rats with Ang II-induced hypertension. Normotensive rats received for 3 wk subcutaneous infusions of Ang II (120 ng/kg per min), or Ang II + PD 123319 (30 mg/kg per d), or Ang II + losartan (10 mg/kg per d) or PD 123319 alone, and were compared with control animals. In normotensive animals, chronic blockade of AT2 receptors did not affect the plasma level of angiotensin II and the vascular reactivity to angiotensin II mediated by the AT1 receptor. Chronic blockade of AT1I in rats receiving Ang II resulted in normal arterial pressure, but it induced significant aortic hypertrophy and fibrosis. Chronic blockade of AT2 receptors in Ang II-induced hypertensive rats had no effect on arterial pressure, but antagonized the effect of Ang II on arterial hypertrophy and fibrosis, suggesting that in vivo vasotrophic effects of Ang II are at least partially mediated via AT2 subtype receptors.
Levy
B I
BI
Institut National de la Santé et de la Recherche Médicale, Unit 141, Université Denis Diderot, Paris, France.
Benessiano
J
J
Henrion
D
D
Caputo
L
L
Heymes
C
C
Duriez
M
M
Poitevin
P
P
Samuel
J L
JL
D000804:Angiotensin II / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003094:Collagen / Q000032:analysis; D004549:Elastin / Q000032:analysis; D005355:Fibrosis; D006973:Hypertension / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D006984:Hypertrophy; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007263:Infusions, Parenteral; D019808:Losartan; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology*; D010656:Phenylephrine / Q000494:pharmacology; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D010656:Phenylephrine; D003094:Collagen; D004549:Elastin; D019808:Losartan