Abstract-The angiotensin II type 2 (AT 2 ) receptor is present in rat kidney; however, its function is not well understood.The purpose of this study was to evaluate the role of the AT 2 receptor in blood pressure (BP) regulation. The effects of selective inhibition of the renal AT 2 receptor with phosphorothioated antisense oligodeoxynucleotide (AS-ODN) were examined in conscious uninephrectomized rats. Oligodeoxynucleotides (AS-ODN or scrambled [S-ODN]) were infused directly into the renal interstitial space by using an osmotic pump at 1 L/h for 7 days. Texas red-labeled AS-ODN was distributed in renal tubules in the infused but not the contralateral kidney of normal rats. Continuous renal interstitial infusion of the AS-ODN, but not S-ODN, caused a significant (PϽ0.01) increase in BP 1 to 5 days after the initiation of the infusion. AS-ODN-treated rats experienced an increase in systolic BP from 109Ϯ4 to 130Ϯ4 mm Hg (nϭ8, PϽ0.01), whereas S-ODN-treated (nϭ8) and vehicle-treated (nϭ8) rats did not show any significant change in BP. On day 5 of the oligodeoxynucleotide infusion, AS-ODN-treated rats exhibited a greater pressor response to systemic angiotensin II infusion (30 ng/kg per hour) than did S-ODN-treated rats (PϽ0.01). Renal interstitial fluid cGMP decreased from 11.9Ϯ0.8 to 3.6Ϯ0.5 pmol/mL (PϽ0.001), and bradykinin decreased from 0.05Ϯ0.05 to 0.18Ϯ0.03 ng/mL (PϽ0.001) in response to AS-ODN, but they were not significantly changed in response to S-ODN. Key Words: blood pressure Ⅲ receptors, angiotensin II Ⅲ hypertension, experimental Ⅲ kidney Ⅲ rats A ngiotensin II (Ang II) is a vasoactive peptide that plays an important role in blood pressure (BP) regulation. Ang II exerts its physiological effects by interacting with 1 of 2 major Ang II receptors, AT 1 or AT 2 . The cDNAs that encode the AT 1 and AT 2 receptors have been cloned, and their cell-signaling pathways have been defined. Ang II has equal affinity for AT 1 and AT 2 receptors. The 2 receptors share a sequence homology of Ϸ34%, and their cDNAs are 91% identical in their nucleotide sequences within their coding regions but only 60% identical in their untranslated regions. Each receptor subtype has distinctive functional properties and cell-signaling mechanisms. 1 The vast majority of the known functions of Ang II result from its interaction with the AT 1 receptor, which mediates renal afferent and efferent arteriolar vasoconstriction, decreases glomerular filtration rate and renal plasma flow, and stimulates sodium and fluid reabsorption in the proximal tubules as well as cell growth and differentiation. [2][3][4][5] The AT 1 receptor has been localized to the brain, peripheral blood vessels, adrenal gland, heart, and kidney. 1,5 Relatively little is known about the AT 2 receptor compared with the AT 1 receptor. 6 AT 2 receptor mRNA has been localized to the rat adrenal gland, heart, and brain, and the receptor protein has been identified by immunohistochemistry and Western blot in rat kidney and heart. 7-11 AT 2 receptor expression is also known...
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