Vascular response to angiotensin II is exaggerated through an upregulationof AT1 receptor in AT2 knockout mice

Blood pressure is elevated and presser response to angiotensin II (Ang II) is exaggerated in AT2 null mice. The purpose of the present study was to el ucidate the mechanism for the increased responsiveness to Ang II in the mic e. The contraction of aortic strips generated by Ang II was significantly g reater in the AT2 gene-deleted mice than the control, which was completely abolished by AT1 antagonist losartan, The aortic content of AT1 receptor wa s significantly increased (P < 0.05, n = 5) in the AT2 null mice (212 +/- 5 8.2 fmol/mg protein) compared with the control (98.2 +/- 55.9 fmol/mg prote in). While both AT1 and AT2 mRNAs were expressed in the aorta of the contro l mice, only AT1 mRNA was expressed in the AT2 knockout mice. The expressio n 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 demons trated that the increased vascular reactivity to Ang II in AT2 knockout mic e is at least partly due to an increased vascular AT1 receptor expression a nd suggested that AT2 counteracts AT1-mediated vascular action of Ang II th rough downregulation of AT1 receptor by a crosstalk between these receptors by some as yet unknown mechanisms. (C) 1999 Academic Press.