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Mechanism of impaired afferent arteriole myogenic response in Dahl salt-sensitive rats: role of 20-HETE
- Source :
- American Journal of Physiology - Renal Physiology; September 2014, Vol. 307 Issue: 5 pF533-F538, 6p
- Publication Year :
- 2014
-
Abstract
- The afferent arteriole (Af-Art) controls glomerular capillary pressure, an important determinant of glomerular injury. Af-Art myogenic response is mediated by ATP, and ATP signaling is in turn mediated by 20-HETE. Dahl salt-sensitive rats (Dahl SS) have decreased renal 20-HETE production. We hypothesized that Dahl SS have an impaired myogenic response and constrictor response to ATP, due to decreased 20-HETE. Af-Arts from Dahl SS or Dahl salt-resistant rats (Dahl SR) were microdissected and perfused. When myogenic response was induced by increasing Af-Art perfusion pressure from 60 to 140 mmHg, luminal Af-Art diameter decreased in Dahl SR but not in Dahl SS (−3.1 ± 0.8 vs. 0.5 ± 0.8 μm, P< 0.01). The 20-HETE antagonist 20-HEDE (10−6M) blocked the myogenic response in Dahl SR but had no effect in Dahl SS. Addition of a subconstrictor concentration of 20-HETE (but not a subconstrictor concentration of norepinephrine) restored the myogenic response in Dahl SS. We then perfused Af-Arts at 60 mmHg and tested the effects of the ATP analog α,β-methylene-ATP (10−6M). Maximum ATP-induced constriction was attenuated in Dahl SS compared with Dahl SR (1.5 ± 0.5 vs. 7.4 ± 0.8 μm, P< 0.001). 20-HEDE attenuated ATP-induced Af-Art constriction in Dahl SR but not in Dahl SS, and consequently, ATP-induced constriction was no longer different between strains. In conclusion, Dahl SS have an impaired myogenic response and ATP-induced Af-Art constriction due to a decrease in Af-Art 20-HETE. The impaired myogenic responses may contribute to the nephrosclerosis that develops in Dahl SS.
Details
- Language :
- English
- ISSN :
- 1931857x and 15221466
- Volume :
- 307
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- American Journal of Physiology - Renal Physiology
- Publication Type :
- Periodical
- Accession number :
- ejs33674727
- Full Text :
- https://doi.org/10.1152/ajprenal.00283.2014