In:
Physiology, American Physiological Society, Vol. 38, No. S1 ( 2023-05)
Abstract:
We previously reported that global deletion of angiotensin II (Ang II) AT 1a receptors significantly lowered basal blood pressure and impaired urine concentration in mice. As we also demonstrated that renomedullary interstitial cells (RMICs) of the kidney expressed a high level of AT 1 (AT 1a ) receptors, we hypothesized that AT 1a receptors in RMICs may play an important physiological role in maintaining basal blood pressure and urine concentration homeostasis. To test the hypothesis, we generated a novel mouse model with deletion of AT 1a receptors selectively in the RMICs of the kidney medulla using inducible Tenascin-C-CreER2/Agtr1a f/f recombination approach (RMIC- Agtr1a -/- ) in the present study. Adult male wildtype (WT) and RMIC- Agtr1a -/- mice (n=10-18 per group) were phenotyped under basal conditions and treated with or without a slow pressor dose of Ang II infusion via an osmotic minipump (~500 μg/kg/day, i.p.) for 2 weeks to determine the roles of AT 1a receptors in RMICs in maintaining basal blood pressure and urine concentration homeostasis and in the development of Ang II-induced hypertension. Under basal conditions, telemetry systolic blood pressure was significantly lower in adult male RMIC- Agtr1a -/- than WT mice (WT: 122 ± 4 mmHg vs. RMIC-Agtr1a-/-: 102 ± 3 mmHg, P 〈 0.01). This hypotensive phenotype in RMIC- Agtr1a -/- mice was associated with significant decreases in 24 h urine output (WT: 1.56 ± 0.15 mL/24 h vs. RMIC- Agtr1a -/- : 0.98 ± 0.13 mL/24 h, P 〈 0.01), urinary sodium (WT: 207.9 ± 7.3 μmol/24 h vs. RMIC- Agtr1a -/- : 145.2 ± 5.4 μmol/24 h, P 〈 0.01), and potassium excretion (WT: 221.0 ± 6.7 μmol/24 h vs. RMIC-Agtr1a-/-: 160.8 ± 10.6 μmol/24 h, P 〈 0.01), respectively. Moreover, urine osmolality was markedly decreased in RMIC- Agtr1a -/- mice even though 24 h urine output was lowered (WT: 1724 ± 335 mOsm/Kg H 2 O vs. RMIC- Agtr1a -/- : 1128 ± 102 mOsm/Kg H 2 O, P 〈 0.01). In response to Ang II infusion, telemetry systolic blood pressure increased to 148 ± 5 mmHg in WT mice, but it increased only to 129 ± 8 mmHg in RMIC- Agtr1a -/- mice ( P 〈 0.01). Furthermore, Ang II infusion for 2 weeks failed to alter urine osmolality in RMIC- Agtr1a -/- mice (1226 ± 110 mOsm/Kg H 2 O, n.s.). In conclusion, we demonstrated for the 1st time that AT 1a receptors in RMICs of the kidney medulla play a key role in physiologically maintaining basal blood pressure homeostasis and urine concentration, as well as in the development of Ang II-induced hypertension. R01DK123144, R01DK067299, R01DK102429 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Type of Medium:
Online Resource
ISSN:
1548-9213
,
1548-9221
DOI:
10.1152/physiol.2023.38.S1.5730096
Language:
English
Publisher:
American Physiological Society
Publication Date:
2023
detail.hit.zdb_id:
3115360-4
detail.hit.zdb_id:
2005759-3
SSG:
12
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