期刊
HYPERTENSION
卷 51, 期 2, 页码 460-465出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.107.103242
关键词
angiotensin; sodium; natriuresis; angiotensin III; AT(2) receptor; AT(1) receptor
资金
- NIDDK NIH HHS [T32 DK-07646] Funding Source: Medline
In the kidney, angiotensin II (Ang II) is metabolized to angiotensin III (Ang III) by aminopeptidase A (APA). In turn, Ang III is metabolized to angiotensin IV by aminopeptidase N (APN). Renal interstitial (RI) infusion of Ang III, but not Ang II, results in angiotensin type-2 receptor (AT(2)R)-mediated natriuresis. This response is augmented by coinfusion of PC-18, a specific inhibitor of APN. The present study addresses the hypotheses that Ang II conversion to Ang III is critical for the natriuretic response. Sprague-Dawley rats received systemic angiotensin type-1 receptor (AT(1)R) blockade with candesartan (CAND; 0.01 mg/kg/min) for 24 hours before and during the experiment. After a control period, rats received either RI infusion of Ang II or Ang II + PC-18. The contralateral kidney received a RI infusion of vehicle in all rats. Mean arterial pressure (MAP) was monitored, and urinary sodium excretion rate (UNaV) was calculated separately from experimental and control kidneys for each period. In contrast to Ang II-infused kidneys, UNaV from Ang II + PC-18-infused kidneys increased from a baseline of 0.03+/-0.01 to 0.09+/-0.02 mu mol/min (P<0.05). MAP was unchanged by either infusion. RI addition of PD-123319, an AT(2)R antagonist, inhibited the natriuretic response. Furthermore, RI addition of EC-33, a selective APA inhibitor, abolished the natriuretic response to Ang II + PC-18. These data demonstrate that RI addition of PC-18 to Ang II enables natriuresis mediated by the AT(2)R, and that conversion of Ang II to Ang III is critical for this response.
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