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Sex differences in angiotensin II-induced hypertension and kidney injury: role of AT1a receptors in the proximal tubule of the kidney.
- Source :
- Clinical Science; Aug2021, Vol. 135 Issue 15, p1825-1843, 19p
- Publication Year :
- 2021
-
Abstract
- In the present study, we tested the hypothesis that there are significant sex differences in angiotensin II (Ang II)-induced hypertension and kidney injury using male and female wildtype (WT) and proximal tubule-specific AT1a receptor knockout mice (PT-Agtr1a-/-). Twelve groups (n=8-12 per group) of adult male and female WT and PT-Agtr1a-/- mice were infused with a pressor dose of Ang II via osmotic minipump for 2 weeks (1.5 mg/kg/day, i.p.) and simultaneously treated with or without losartan (20 mg/kg/day, p.o.) to determine the respective roles of AT1a receptors in the proximal tubules versus systemic tissues. Basal systolic, diastolic, and mean arterial pressure were approximately 13+- 3 mmHg lower (P<0.01), while basal 24-h urinary Na+, K+, and Cl- excretion were significantly higher in both male and female PT-Agtr1a-/- mice than WT controls (P<0.01) without significant sex differences between different strains. Both male and female WT and PT-Agtr1a-/- mice developed hypertension (P<0.01), and the magnitudes of the pressor responses to Ang II were similar between male and female WT and PT-Agtr1a-/- mice (n.s.). Likewise, Ang II-induced hypertension was significantly attenuated in both male and female PT-Agtr1a-/- mice (P<0.01). Furthermore, losartan attenuated the hypertensive responses to Ang II to similar extents in both male and female WT and PT-Agtr1a-/- mice. Finally, Ang II-induced kidney injury was attenuated in PT-Agtr1a-/- mice (P<0.01). In conclusion, the present study demonstrates that deletion of AT1a receptors in the proximal tubules of the kidney attenuates Ang II-induced hypertension and kidney injury without revealing significant sex differences. [ABSTRACT FROM AUTHOR]
- Subjects :
- PROXIMAL kidney tubules
HYPERTENSION
KIDNEY injuries
ANGIOTENSINS
ANGIOTENSIN II
Subjects
Details
- Language :
- English
- ISSN :
- 01435221
- Volume :
- 135
- Issue :
- 15
- Database :
- Complementary Index
- Journal :
- Clinical Science
- Publication Type :
- Academic Journal
- Accession number :
- 151848823
- Full Text :
- https://doi.org/10.1042/CS20201574