Luminal flow regulates NO and O2 along the nephron

PD Cabral, JL Garvin - American Journal of Physiology …, 2011 - journals.physiology.org
American Journal of Physiology-Renal Physiology, 2011journals.physiology.org
Urinary flow is not constant but in fact highly variable, altering the mechanical forces (shear
stress, stretch, and pressure) exerted on the epithelial cells of the nephron as well as solute
delivery. Nitric oxide (NO) and superoxide (O2−) play important roles in various processes
within the kidney. Reductions in NO and increases in O2− lead to abnormal NaCl and water
absorption and hypertension. In the last few years, luminal flow has been shown to be a
regulator of NO and O2− production along the nephron. Increases in luminal flow enhance …
Urinary flow is not constant but in fact highly variable, altering the mechanical forces (shear stress, stretch, and pressure) exerted on the epithelial cells of the nephron as well as solute delivery. Nitric oxide (NO) and superoxide (O2) play important roles in various processes within the kidney. Reductions in NO and increases in O2 lead to abnormal NaCl and water absorption and hypertension. In the last few years, luminal flow has been shown to be a regulator of NO and O2 production along the nephron. Increases in luminal flow enhance fluid, Na, and bicarbonate transport in the proximal tubule. However, we know of no reports directly addressing flow regulation of NO and O2 in this segment. In the thick ascending limb, flow-stimulated NO and O2 formation has been extensively studied. Luminal flow stimulates NO production by nitric oxide synthase type 3 and its translocation to the apical membrane in medullary thick ascending limbs. These effects are mediated by flow-induced shear stress. In contrast, flow-induced stretch and NaCl delivery stimulate O2 production by NADPH oxidase in this segment. The interaction between flow-induced NO and O2 is complex and involves more than one simply scavenging the other. Flow-induced NO prevents flow from increasing O2 production via cGMP-dependent protein kinase in thick ascending limbs. In macula densa cells, shear stress increases NO production and this requires that the primary cilia be intact. The role of luminal flow in NO and O2 production in the distal tubule is not known. In cultured inner medullary collecting duct cells, shear stress enhances nitrite accumulation, a measure of NO production. Although much progress has been made on this subject in the last few years, there are still many unanswered questions.
American Physiological Society