Nuclear angiotensin II type 2 (AT2) receptors are functionally linked to nitric oxide production in the ovine kidney cortex, as demonstrated by increased NO production with ANG II that was abolished by the AT2 antagonist PD123319.
Nuclear AT2 receptors in the sheep kidney are functionally linked to nitric oxide production, supporting the existence of a functional intracellular renin-angiotensin system.
p-value: p=<0.05
Expression of nuclear angiotensin II type 1 (AT(1)) receptors in rat kidney provides further support for the concept of an intracellular renin-angiotensin system. Thus we examined the cellular distribution of renal ANG II receptors in sheep to determine the existence and functional roles of intracellular ANG receptors in higher order species. Receptor binding was performed using the nonselective ANG II antagonist (125)I-Sar(1),Thr(8)-ANG II ((125)I-sarthran) with the AT(1) antagonist losartan (LOS) or the AT(2) antagonist PD123319 (PD) in isolated nuclei (NUC) and plasma membrane (PM) fractions obtained by differential centrifugation or density gradient separation. In both fetal and adult sheep kidney, PD competed for the majority of cortical NUC (> or =70%) and PM (> or =80%) sites while LOS competition predominated in medullary NUC (> or =75%) and PM (> or =70%). Immunodetection with an AT(2) antibody revealed a single approximately 42-kDa band in both NUC and PM extracts, suggesting a mature molecular form of the NUC receptor. Autoradiography for receptor subtypes localized AT(2) in the tubulointerstitium, AT(1) in the medulla and vasa recta, and both AT(1) and AT(2) in glomeruli. Loading of NUC with the fluorescent nitric oxide (NO) detector DAF showed increased NO production with ANG II (1 nM), which was abolished by PD and N-nitro-l-arginine methyl ester, but not LOS. Our studies demonstrate ANG II receptor subtypes are differentially expressed in ovine kidney, while nuclear AT(2) receptors are functionally linked to NO production. These findings provide further evidence of a functional intracellular renin-angiotensin system within the kidney, which may represent a therapeutic target for the regulation of blood pressure.
Gwathmey et al. (Thu,) conducted a other in Normal physiology (animal model) (n=20). Angiotensin II (ANG II) and receptor antagonists (losartan, PD123319) vs. Control (buffer alone) was evaluated on Nitric oxide (NO) production in isolated cortical nuclei (p=<0.05). Nuclear angiotensin II type 2 (AT2) receptors are functionally linked to nitric oxide production in the ovine kidney cortex, as demonstrated by increased NO production with ANG II that was abolished by the AT2 antagonist PD123319.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: