Increased AT₁ receptors in adrenal gland of AT₂ receptor gene-disrupted mice

Angiotensin II (Ang II) AT₂ receptor-gene disrupted mice have increased systemic blood pressure and response to exogenous Angiotensin II. To clarify the mechanism of these changes, we studied adrenal AT₁ receptor expression and mRNA by receptor autoradiography and in situ hybridization in female AT₂ receptor-gene disrupted mice (agtr 2-/-) and wild-type controls (agtr 2+/+). We found high expression of AT₁ receptor binding and mRNA in adrenal zona glomerulosa of female wild-type mice. AT₂ receptors and mRNA were highly expressed in adrenal medulla of wild-type mice, but were not detected in zona glomerulosa. There was no AT₂ receptor binding or mRNA in adrenal glands of AT₂ receptor-gene disrupted mice. In these animals, AT₁ receptor binding and mRNA were increased in adrenal zona glomerulosa and AT₁ receptor mRNA was increased in the adrenal medulla when compared with wild-type animals. The present data support the hypothesis of an interaction or cross talk between AT₂ and AT₁ receptors in adrenal gland. The significant increase in AT₁ receptor expression in the absence of AT₂ receptor transcription may be partially responsible for the increased blood pressure and for the enhanced response to exogenously administered Angiotensin II in this model. Published by Elsevier Science B.V.