The subtype 2 angiotensin receptor regulates renal prostaglandin F2 alpha formation in conscious rats.
The angiotensin AT1 receptor mediates renal prostaglandin (PG) E2 production through stimulation of phospholipase A2. Blockade of the AT2 receptor potentiates the angiotensin II-induced increase in PGE2 levels. In the kidney, PGE2 is converted to PGF2 alpha mainly by the enzyme PGE 9-ketoreductase. We hypothesized that the conversion of PGE2 to PGF2 alpha is inhibited by AT2 receptor blockade, resulting in the observed increase in PGE2 levels. Using a microdialysis technique, we monitored changes in renal interstitial fluid PGE2 and PGF2 alpha in response to 5 days of sodium depletion alone or a combination of sodium depletion and intravenous infusion of the AT1 receptor blocker losartan or the AT2 receptor blocker PD-123319 in conscious rats. We utilized the PGF2 alpha-to-PGE2 ratio as an indirect measure of the rate of renal PGF2 alpha formation. Sodium depletion increased PGE2, PGF2 alpha, and the PGF2 alpha-to-PGE2 ratio. During sodium depletion, losartan decreased PGE2 and PGF2 alpha and did not change the PGF2 alpha-to-PGE2 ratio. In contrast, PD-123319 increased PGE2, decreased PGF2 alpha, and decreased the PGF2 alpha-to-PGE2 ratio. These data demonstrate that activation of the renin-angiotensin system during sodium depletion physiologically increases renal conversion of PGE2 to PGF2 alpha. The increase in renal production of PGF2 alpha is mediated through stimulation of the angiotensin AT2 receptor.
Siragy
H M
HM
Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Carey
R M
RM
D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004039:Diet, Sodium-Restricted; D015237:Dinoprost / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D005110:Extracellular Space / Q000502:physiology; D005260:Female; D006706:Homeostasis; D007093:Imidazoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D019808:Losartan; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology*; D012982:Sodium, Dietary; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D012982:Sodium, Dietary; D013777:Tetrazoles; D000804:Angiotensin II; D015237:Dinoprost; D019808:Losartan; D015232:Dinoprostone