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Impaired renal NCC function and expression: a mechanism driving norepinephrine evoked salt‐sensitive hypertension? (857.6)
Author(s) -
Walsh Kathryn,
Wainford Richard
Publication year - 2014
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.28.1_supplement.857.6
Subject(s) - hexamethonium , natriuresis , endocrinology , medicine , hydrochlorothiazide , chemistry , saline , norepinephrine , diuresis , renal function , blood pressure , stimulation , dopamine
Aim: These studies test the hypothesis that impaired renal NCC regulation is a mechanism underlying the development of norepinephrine (NE) evoked salt‐sensitive hypertension in Sprague‐Dawley (SD) rats. Methods: SD rats receiving a s.c. saline vehicle, NE (600ng/min), DMSO/saline vehicle (50:50), or hydrochlorothiazide (HCTZ 4mg/kg/d) and NE infusion were fed a 0.4% (NS) or high 8% NaCl (HS) diet for 14 days. On day 14, MAP, MAP response to i.v. hexamethonium (30mg/kg) and peak natriuresis to i.v. HCTZ (2mg/kg) infusion was assessed and NCC immunoblotting was performed on kidney cortex tissue. Results: NE significantly increased MAP and vascular sympathetic tone. HS exacerbated NE induced hypertension, induced up‐regulation of NCC protein levels and prevented dietary sodium stimulated reduction in HCTZ evoked natriuresis. HCTZ + NE co‐infusion abolished the salt‐sensitive component of NE induced hypertension.s.c. saline vehicle s.c. NE s.c. DMSO/saline s.c. NE + HCTZNS HS NS HS HS HS MAP (mmHg) 124±2 124±1 151±3Ï• 171±4*≠134±4 152±3≠ψτ Peak ΔMAP to hexamethonium (mmHg) ‐61±4 ‐66±3 ‐77±6Ï• ‐81±8≠‐57±4.5 ‐69±3Ï„ Peak ΔUNaV to HCTZ (μeq/min) 8.7±0.3 7.2±0.7* 11.1±1.1 Ï• 10.8±0.4≠6.3±1.3 0.4±0.2 ≠ψτ NCC expression(ODU/mm 2 normalized to GAPDH) TBD TBD 0.15±0.02 0.27±0.06* n.d. n.d.*p<0.05 vs respective NS gp; ϕp<0.05 vs vehicle NS gp; ≠p<0.05 vs vehicle HS gp; ψp<0.05 vs DSMO vehicle; τp<0.05 vs NE + HS gp; n=4‐6/gp. Conclusion: These findings reveal that the combination of high salt intake and excess NE evokes the development of salt‐sensitive hypertension which consequently results in impaired NCC function and increased protein expression. These results contrast the established down‐regulation of NCC expression and circulating NE levels observed during high salt‐intake in salt‐resistant rat phenotypes and provides a new insight into the mechanisms underlying the influence of sympathoexcitation on the kidney in hypertension. Grant Funding Source : R01HL107330 & K02HL112718A1