Increased AT(1) receptors in adrenal gland of AT(2) receptor gene-disrupted mice.
Angiotensin II (Ang II) AT(2) 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 AT(1) receptor expression and mRNA by receptor autoradiography and in situ hybridization in female AT(2) receptor-gene disrupted mice (agtr 2-/-) and wild-type controls (agtr 2+/+). We found high expression of AT(1) receptor binding and mRNA in adrenal zona glomerulosa of female wild-type mice. AT(2) receptors and mRNA were highly expressed in adrenal medulla of wild-type mice, but were not detected in zona glomerulosa. There was no AT(2) receptor binding or mRNA in adrenal glands of AT(2) receptor-gene disrupted mice. In these animals, AT(1) receptor binding and mRNA were increased in adrenal zona glomerulosa and AT(1) 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 AT(2) and AT(1) receptors in adrenal gland. The significant increase in AT(1) receptor expression in the absence of AT(2) receptor transcription may be partially responsible for the increased blood pressure and for the enhanced response to exogenously administered Angiotensin II in this model.
Saavedra
J M
JM
Section on Pharmacology, National Institute of Mental Health, 10 Center Drive MSC 1514, Building 10, Room 2D-57, Bethesda, MD 20892, USA. Saavedrj@irp.nimh.nih.gov
Armando
I
I
Terrón
J A
JA
Falcón-Neri
A
A
Jöhren
O
O
Häuser
W
W
Inagami
T
T
D000313:Adrenal Medulla / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D007093:Imidazoles / Q000494:pharmacology; D017403:In Situ Hybridization; D019808:Losartan / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism*
D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan