Increased AT(1) receptor expression and mRNA in kidney glomeruli of AT(2) receptor gene-disrupted mice.
The proposed feedback between angiotensin II AT(2) and AT(1) receptors prompted us to study AT(1) receptor expression in kidneys of male AT(2) receptor-gene disrupted mice (agtr2 -/y). In wild-type (agtr2 +/y) mice, AT(1) receptor binding and mRNA is abundant in glomeruli, and AT(1) receptor binding is also high in the inner stripe of the outer medulla. AT(2) receptors are scarce, primarily associated to cortical vascular structures. In agtr2 -/y mice, AT(1) receptor binding and mRNA were increased in the kidney glomeruli, and AT(1) receptor binding was higher in the rest of the cortex and outer stripe of the outer medulla, but not in its inner stripe, indicating different cellular regulation. Although AT(2) receptor expression is very low in male agtr 2 +/y mice, their gene disruption alters AT(1) receptor expression. AT(1) upregulation alone may explain the AT(2) gene-disrupted mice phenotype such as increased blood pressure, higher sensitivity to angiotensin II, and altered renal function. The indirect AT(1)/AT(2) receptor feedback could have clinical significance because AT(1) antagonists are widely used in medical practice.
Saavedra
J M
JM
Section on Pharmacology, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Saavedrj@irp.nimh.nih.gov
Häuser
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W
Ciuffo
G
G
Egidy
G
G
Hoe
K L
KL
Jöhren
O
O
Sembonmatsu
T
T
Inagami
T
T
Armando
I
I
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure / Q000187:drug effects; D003433:Crosses, Genetic; D005246:Feedback; D005838:Genotype; D007093:Imidazoles / Q000494:pharmacology; D007672:Kidney Cortex / Q000098:blood supply / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism*; D007679:Kidney Medulla / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009928:Organ Specificity; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology*; D014158:Transcription, Genetic
D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan