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ETB Receptor Signaling Through NOS1 Regulates Na and NOX Excretion Following an Acute Salt Load
Author(s) -
Cruthirds Danielle L,
Pollock David M,
Pollock Jennifer S
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1328-d
ET B receptor deficient ( sl/sl ) rats lack a functional ET B signaling pathway in non‐neuronal cells. Our laboratory has shown that sl/sl rats have attenuated NOS1 activity in the renal inner medulla suggesting that the endothelin receptor system regulates NOS activity. Experiments were designed to test the hypothesis that the endothelin B (ET B ) receptor activates NO production via NO synthase1 (NOS1) facilitating excretion of an acute salt load. Following a 2‐day baseline period, rats (n=6) received a salt challenge of 460 μEq Na. Wild‐type (+/+) rats excreted 74 + 1% of the Na load (442 + 7 μEq Na) within the first 12 hrs post‐challenge, while sl/sl rats excreted only 7 + 1% (42 + 4 μEq Na) in the first 12 hrs, p<.0001. NOS1 inhibition with 7‐NI (50 mg/kg) blunted excretion of the Na load in +/+ rats with only 4 + 0.4% (22 + 2 μEq Na vs. 442 + 7 μEq Na, p<.0001), excreted in the first 12 hrs post‐challenge, while 7‐NI treatment did not have any further attenuation of Na excretion in sl/sl rats. NO X excretion in +/+ rats increased from baseline following the salt load (36 + 4 mmoles/12 hrs, p<.003) while 7‐NI treatment attenuated this increase (7 + 2 mmoles/12 hrs). Compared to +/+ rats, NO X excretion in sl/sl rats was blunted following the salt load (17 + 2 mmoles/12 hrs, p<.05). Treatment of sl/sl rats with 7‐NI had no further effect on NO X excretion. In conclusion, these results provide in vivo evidence for ET B receptor activation facilitating the excretion of an acute salt load by activation of NOS1 and NO production.