Juxtaglomerular cell complex in the regulation of renal salt excretion

Luminal NaCl concentration at the macula densa (MD) has the two established effects of regulating glomerular arteriolar resistance and renin secretion. Tubuloglomerular feedback (TGF), the inverse relationship between MD NaCl concentration and glomerular filtration rate (GFR), stabilizes distal salt delivery and thereby NaCl excretion in response to random perturbations unrelated to changes in body salt balance. Control of vasomotor tone by TGF is exerted primarily by NaCl transport-dependent changes in local adenosine concentrations. During long-lasting perturbations of MD NaCl concentration, control of renin secretion becomes the dominant function of the MD. The potentially maladaptive effect of TGF under chronic conditions is prevented by TGF adaptations, permitting adjustments in GFR to occur. TGF adaptation is mechanistically coupled to the end point targeted by chronic deviations in MD NaCl, the rate of local and systemic angiotensin II generation. MD control of renin secretion is the result of the coordinated action of local mediators that include nitric oxide synthase (NOS) and cyclooxygenase (COX) products. Thus vascular smooth muscle cell activation during high MD transport and granular cell activation during low MD transport is achieved by different extracellular mediators. The coordinated regulation of NOS I and COX-2 expression in MD cells and of renin expression in granular cells suggests that control of juxtaglomerular regulation of gene transcription or mRNA metabolism may be another consequence of a chronic alteration in MD NaCl concentration.