Vascular response to angiotensin II is exaggerated through an upregulation of AT1 receptor in AT2 knockout mice.
Blood pressure is elevated and pressor response to angiotensin II (Ang II) is exaggerated in AT2 null mice. The purpose of the present study was to elucidate the mechanism for the increased responsiveness to Ang II in the mice. The contraction of aortic strips generated by Ang II was significantly greater in the AT2 gene-deleted mice than the control, which was completely abolished by AT1 antagonist losartan. The aortic content of AT1 receptor was significantly increased (P < 0.05, n = 5) in the AT2 null mice (212 +/- 58.2 fmol/mg protein) compared with the control (98.2 +/- 55.9 fmol/mg protein). While both AT1 and AT2 mRNAs were expressed in the aorta of the control mice, only AT1 mRNA was expressed in the AT2 knockout mice. The expression of AT1 mRNA in the AT2 knockout mice was significantly higher (1.5-fold, P < 0.05, n = 5) than that in the control. The present study clearly demonstrated that the increased vascular reactivity to Ang II in AT2 knockout mice is at least partly due to an increased vascular AT1 receptor expression and suggested that AT2 counteracts AT1-mediated vascular action of Ang II through downregulation of AT1 receptor by a crosstalk between these receptors by some as yet unknown mechanisms.
Tanaka
M
M
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, 8-1 Kawadacho, Tokyo, Shinjuku-ku, 162-8666, Japan.
Tsuchida
S
S
Imai
T
T
Fujii
N
N
Miyazaki
H
H
Ichiki
T
T
Naruse
M
M
Inagami
T
T
D000450:Aldosterone / Q000097:blood; D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001483:Base Sequence; D001667:Binding, Competitive; D017931:DNA Primers; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D011485:Protein Binding; D011945:Receptors, Angiotensin / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000450:Aldosterone; D000803:Angiotensin I