ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2015
Shear stress blunts tubuloglomerular feedback partially mediated by primary cilia and nitric oxide at the macula densa.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 21 citations in OpenAlex.
- A new view of macula densa cell microanatomy.American journal of physiology. Renal physiology · 2021Article
- Sensing of tubular flow and renal electrolyte transport.Nature reviews. Nephrology · 2020Review
- NaHCOHypertension (Dallas, Tex. : 1979) · 2019Article
- Macula Densa SGLT1-NOS1-Tubuloglomerular Feedback Pathway, a New Mechanism for Glomerular Hyperfiltration during Hyperglycemia.Journal of the American Society of Nephrology : JASN · 2019Article
- Activation of the cannabinoid receptor 2 increases renal perfusion.Physiological genomics · 2019Article
- Nitric oxide mediates anomalous tubuloglomerular feedback in rats fed high-NaCl diet after subtotal nephrectomy.American journal of physiology. Renal physiology · 2019Article
- Thick Ascending Limb Sodium Transport in the Pathogenesis of Hypertension.Physiological reviews · 2019Review
- Role of the Primary Cilia on the Macula Densa and Thick Ascending Limbs in Regulation of Sodium Excretion and Hemodynamics.Hypertension (Dallas, Tex. : 1979) · 2017Article
- Effects of Reactive Oxygen Species on Tubular Transport along the Nephron.Antioxidants (Basel, Switzerland) · 2017Review
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The present study tested whether primary cilia on macula densa serve as a flow sensor to enhance nitric oxide synthase 1 (NOS1) activity and inhibit tubuloglomerular feedback (TGF). Isolated perfused macula densa was loaded with calcein red and 4,5-diaminofluorescein diacetate to monitor cell volume and nitric oxide (NO) generation. An increase in tubular flow rate from 0 to 40 nl/min enhanced NO production by 40.0 ± 1.2%. The flow-induced NO generation was blocked by an inhibitor of NOS1 but not by inhibition of the Na/K/2Cl cotransporter or the removal of electrolytes from the perfusate. NO generation increased from 174.8 ± 21 to 276.1 ± 24 units/min in cultured MMDD1 cells when shear stress was increased from 0.5 to 5.0 dynes/cm(2). The shear stress-induced NO generation was abolished in MMDD1 cells in which the cilia were disrupted using a siRNA to ift88. Increasing the NaCl concentration of the tubular perfusate from 10 to 80 mM NaCl in the isolated perfused juxtaglomerular preparation reduced the diameter of the afferent arteriole by 3.8 ± 0.1 μm. This response was significantly blunted to 2.5 ± 0.2 μm when dextran was added to the perfusate to increase the viscosity and shear stress. Inhibition of NOS1 blocked the effect of dextran on TGF response. In vitro, the effects of raising perfusate viscosity with dextran on tubular hydraulic pressure were minimized by reducing the outflow resistance to avoid stretching of tubular cells. These results suggest that shear stress stimulates primary cilia on the macula densa to enhance NO generation and inhibit TGF responsiveness.
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