Renal medullary endothelin-1 is decreased in Dahl salt-sensitive rats

May 27, 2011American journal of physiology. Regulatory, integrative and comparative physiology

Lower levels of a blood vessel signaling molecule in the kidney's inner region of salt-sensitive rats

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Abstract

Dahl salt-resistant rats on a high-salt diet had a six-fold higher urinary endothelin excretion compared to their low sodium intake counterparts.

Dahl salt-sensitive rats showed only a twofold increase in urinary endothelin levels in response to a high sodium intake.
Medullary endothelin concentration was significantly lower in Dahl salt-sensitive rats on a high sodium diet compared to Dahl salt-resistant rats.
Dahl salt-sensitive rats exhibited a significant reduction in medullary ET(B) receptor expression while on a high sodium diet.
Chronic infusion of endothelin-1 into the renal medulla reduced hypertension in Dahl salt-sensitive rats.
A decrease in medullary production of endothelin-1 in Dahl salt-sensitive rats may contribute to the development of salt-sensitive hypertension.

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Although it is well established that the renal endothelin (ET-1) system plays an important role in regulating sodium excretion and blood pressure through activation of renal medullary ET(B) receptors, the role of this system in Dahl salt-sensitive (DS) hypertension is unclear. The purpose of this study was to determine whether the DS rat has abnormalities in the renal medullary endothelin system when maintained on a high sodium intake. The data indicate that Dahl salt-resistant rats (DR) on a high-salt diet had a six-fold higher urinary endothelin excretion than in the DR rats with low Na(+) intake (17.8 ± 4 pg/day vs. 112 ± 44 pg/day). In sharp contrast, urinary endothelin levels increased only twofold in DS rats in response to a high Na(+) intake (13 ± 2 pg/day vs. 29.8 ± 5.5 pg/day). Medullary endothelin concentration in DS rats on a high-Na(+) diet was also significantly lower than DR rats on a high-Na(+) diet (31 ± 2.8 pg/mg vs. 70.9 ± 5 pg/mg). Furthermore, DS rats had a significant reduction in medullary ET(B) receptor expression compared with DR rats while on a high-Na(+) diet. Finally, chronic infusion of ET-1 directly into the renal medulla blunted Dahl salt-sensitive hypertension. These data indicate that a decrease in medullary production of ET-1 in the DS rat could play an important role in the development of salt-sensitive hypertension observed in the DS rat.

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Renal medullary endothelin-1 is decreased in Dahl salt-sensitive rats

Abstract

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