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. 2014 Sep 1;307(5):F533-8.
doi: 10.1152/ajprenal.00283.2014. Epub 2014 Jul 2.

Mechanism of impaired afferent arteriole myogenic response in Dahl salt-sensitive rats: role of 20-HETE

YiLin Ren  1 , Martin A D'Ambrosio  1 , Jeffrey L Garvin  2 , Edward L Peterson  3 , Oscar A Carretero  4
Affiliations

Mechanism of impaired afferent arteriole myogenic response in Dahl salt-sensitive rats: role of 20-HETE

YiLin Ren et al. Am J Physiol Renal Physiol. .

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(-6) M) 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(-6) M). 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.

Keywords: 20-HETE; ATP; afferent arteriole; myogenic response; salt-sensitive hypertension.

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Figures

Fig. 1.
Fig. 1.
Afferent arteriole (Af-Art) response to a stepwise increase in perfusion pressure in Dahl salt-sensitive (SS) and Dahl salt-resistant (SR) rats. When Af-Art pressure was increased from 60 to 140 mmHg, diameter decreased only in Dahl SR but not in Dahl SS rats (**P < 0.01 Dahl SS vs. Dahl SR).
Fig. 2.
Fig. 2.
A: effect of 20-HEDE on the myogenic response in Dahl SR Af-Arts. 20-HEDE significantly blocked pressure-induced constriction (*P < 0.05, **P < 0.01, ***P < 0.001 control vs. 20-HEDE). B: effect of 20-HEDE on the myogenic response in Sprague-Dawley (SD) rat. 20-HEDE significantly blocked pressure-induced constriction (**P < 0.01, ***P < 0.001 control vs. 20-HEDE). C: effect of 20-HEDE on the myogenic response in Dahl SS Af-Arts. 20-HEDE has no effect on Af-Art diameter.
Fig. 3.
Fig. 3.
A: effect of a subconstrictor concentration of exogenous 20-HETE on the myogenic response in Dahl SS rats. Addition of 20-HETE enhanced pressure-induced constriction (**P < 0.01 control vs. 20-HETE). B: effect of a subconstrictor concentration of exogenous norepinephrine (NE) on the myogenic response in Dahl SS rats. Unlike 20-HETE, addition of NE has no effect on pressure-induced constriction.
Fig. 4.
Fig. 4.
Effect of exogenous ATP on Af-Art constriction. Addition of 10−6 M ATP constricted Af-Arts more in Dahl SR than in Dahl SS rats (***P < 0.001 Dahl SS vs. Dahl SR).
Fig. 5.
Fig. 5.
A: effect of 20-HEDE on ATP-induced Af-Art constriction in Dahl SR rats. 20-HEDE significantly blocked ATP-induced Af-Art constriction (**P < 0.01 control vs. 20-HEDE). B: time control of ATP-induced Af-Art constriction in Dahl SR rats. C: effect of 20-HEDE on ATP-induced Af-Art constriction in Dahl SS rats. 20-HEDE has no effect on ATP-induced Af-Art constriction. D: time control of ATP-induced Af-Art constriction in Dahl SS rats.
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