Tubular control of renin synthesis and secretion.
The intratubular composition of fluid at the tubulovascular contact site of the juxtaglomerular apparatus serves as regulatory input for secretion and synthesis of renin. Experimental evidence, mostly from in vitro perfused preparations, indicates an inverse relation between luminal NaCl concentration and renin secretion. The cellular transduction mechanism is initiated by concentration-dependent NaCl uptake through the Na-K-2Cl cotransporter (NKCC2) with activation of NKCC2 causing inhibition and deactivation of NKCC2 causing stimulation of renin release. Changes in NKCC2 activity are coupled to alterations in the generation of paracrine factors that interact with granular cells. Among these factors, generation of PGE2 in a COX-2-dependent fashion appears to play a dominant role in the stimulatory arm of tubular control of renin release. [NaCl] is a determinant of local PG release over an appropriate concentration range, and blockade of COX-2 activity interferes with the NaCl dependency of renin secretion. The complex array of local paracrine controls also includes nNOS-mediated synthesis of nitric oxide, with NO playing the role of a modifier of the intracellular signaling pathway. A role of adenosine may be particularly important when [NaCl] is increased, and at least some of the available evidence is consistent with an important suppressive effect of adenosine at higher salt concentrations.
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10, Rm 4D50, NIDDK, NIH, 10 Center Drive MSC 1370, Bethesda, MD 20892, USA. jurgens@intra.niddk.nih.gov
Jurgen
J
Schnermann
Josephine P
JP
Briggs
D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006801:Humans; D007606:Juxtaglomerular Apparatus / Q000378:metabolism; D007684:Kidney Tubules / Q000033:anatomy & histology / Q000378:metabolism* / Q000502:physiology; D011453:Prostaglandins / Q000378:metabolism; D012083:Renin / Q000096:biosynthesis* / Q000378:metabolism; D012084:Renin-Angiotensin System; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism
D011453:Prostaglandins; D028021:Sodium-Potassium-Chloride Symporters; D051546:Cyclooxygenase 2; D012083:Renin