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Activation of Na+/H+ exchanger (NHE) in the macula densa (MD) enhances tubuloglomerular feedback (TGF) in spontaneously hypertensive rats (SHR)
Author(s) -
Fu Yiling,
Lu Yan,
Ge Ying,
Juncos Luis A,
Liu Ruisheng
Publication year - 2012
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.26.1_supplement.875.12
Subject(s) - macula densa , tubuloglomerular feedback , chemistry , endocrinology , sodium–hydrogen antiporter , medicine , superoxide , amiloride , perfusion , renin–angiotensin system , renal function , sodium , biochemistry , blood pressure , enzyme , organic chemistry
NHE stimulates both NO and superoxide production in the MD. We hypothesize activation of NHE enhances NO generation by MD and suppresses TGF in vivo , however, which is impaired in SHR contributing to enhanced TGF response. TGF was determined by measuring maximum changes of stop‐flow pressure, ΔPsf, while increasing tubular perfusion from 0 to 40 nl/min with micropuncture in the absence and presence of a selective NHE inhibitor, 5‐(N,N‐Dimethyl) amiloride (DMA, 10 −4 M,) in the tubular perfusate in 8–9 wk old WKY and SHR. NHE inhibition augmented TGF in WKY (ΔPsf 9.69±0.56 v.s. 12.53±0.57 mmHg, vehicle v.s. DMA, p<0.01), while showed no effect in SHR (10.94 ±1.01 v.s. 11.89±1.03 mmHg). In the presence of L‐NMA (10 −3 M, a NOS inhibitor), NHE inhibition with DMA further enhanced TGF in WKY (12.83±2.04 v.s. 16.63±1.85 mmHg, L‐NMA v.s. L‐NMA plus DMA, p=0.01), while it blunted TGF in SHR (12.45±1.07 v.s. 9.97±0.64 mmHg, p=0.01). In isolated microperfused rabbit juxtaglomerular apparatus, the net NO generation by the MD increased by 287.1% ± 22.1 when switching perfusion solution from 10mM to 80 mM NaCl in the presence of tempol (10 −4 M) to scavenger superoxide, while it increased only 32.3% ± 1.9 when we repeated the switch and blocked NHE with DMA (p<0.01). We conclude that activation of NHE blunts TGF via increasing NO generation by the MD, while this mechanism is impaired in SHR, probably due to the reduced NO bioavailability.