Abstract 033: Identification of s Primary Renal AT 2 Receptor Defect in Spontaneously Hypertensive Rats (SHR)
| Autor: | Weijian Shao, John J Gildea, Brandon A. Kemp, L. G. Navar, Robert M. Carey, Nancy L. Howell, Susanna R. Keller |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
medicine.medical_specialty
Kidney business.industry Sodium Angiotensin III chemistry.chemical_element Angiotensin II Natriuresis Endocrinology medicine.anatomical_structure chemistry Internal medicine Renin–angiotensin system cardiovascular system Internal Medicine medicine business Receptor Endogenous agonist |
| Zdroj: | Hypertension. 72 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hyp.72.suppl_1.033 |
| Popis: | Angiotensin III (Ang III) [des-aspartyl 1 -Ang II] is the predominant endogenous agonist for angiotensin type-2 receptor (AT 2 R)-induced natriuresis in rats. Hypertensive 12 wk-old SHR lack natriuretic responses to Ang III, and renal interstitial (RI) Ang III administration induces natriuresis in 4 wk-old Wistar-Kyoto rats (WKY), but not in 4 wk-old pre-hypertensive SHR. The defect in natriuresis could be explained by the concurrent observation that in WKY, but not SHR, Ang III induced AT 2 R translocation to renal proximal tubule apical plasma membranes and internalization/inactivation of Na + -transporters Na + - H + exchanger-3 (NHE-3) and Na + /K + ATPase (NKA). These findings suggest an Ang III/AT 2 R signaling defect in pre-hypertensive SHR. The present study sought to determine the cause of the defect: (1) accelerated intrarenal Ang III metabolism or (2) a primary AT 2 R (or post-receptor) signaling defect. Selective AT 2 R agonist Compound-21 (C-21) was infused interstitially [20, 40 and 60 ng/kg/min, each dose for 30 min] into experimental (left) kidneys of 4 wk-old WKY and SHR (N=7) pretreated for 24h with systemic infusion of Ang type-1 receptor (AT 1 R) antagonist candesartan (0.01 mg/kg/min by osmotic minipump); vehicle was infused into control (right) kidneys. Pre-infusion urinary Na + excretion (U Na V) was 0.022 ± 0.004 μmol/min in WKY and 0.024 ± 0.005 μmol/min in SHR (P=NS). In WKY, C-21 dose-dependently increased U Na V from 0.022 ± 0.004 to 0.058 ± 0.017, 0.078 ± 0.014 and 0.079 ± 0.079 μmol/min (P=0.01 from pre-infusion and time control kidneys). In contrast, SHR did not increase U Na V in response to C-21 [highest U Na V 0.033 ± 0.007 μmol/min (P=NS from pre-infusion and time control kidneys)]. Mean arterial pressure (MAP) was 64.6 ± 1.80 mmHg in WKY and 76.4 ± 2.2 mmHg (P2 R defect as responsible for increased Na + reabsorption in SHR. |
| Databáze: | OpenAIRE |
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