Altered reactivity of tubuloglomerular feedback.

The efficiency of coupling between salt delivery to the sensing site in the macula densa and the glomerular vascular effector response is altered by changes in extracellular fluid volume, in the amount of dietary protein, and many other conditions, including growth and maturation, and the development of hypertension in Okamoto-Aoki and Milan strains of genetically hypertensive rats. Examination of feedback-mediated responses by perfusion of Henle's loop reveals a tendency for multiple changes in characteristics of feedback curves for SNGFR and SFP. In general, inhibition of TGF activity is evidenced by a smaller maximum glomerular response, reduced reactivity, and a shift in the inflection point to a higher flow rate. The opposite responses are frequently noted during exaggerated TGF activity. It is not known at present whether one or more mechanisms are involved in mediating or modulating the functional correlates of these characteristics. Insight into these functional correlates may be provided by selective, graded inhibition and stimulation of the sensing and effector elements in the feedback loop. Investigations of potential extrarenal mechanisms of resetting indicate that atrial natriuretic factor and an unidentified factor present in the proximal tubular fluid may play a role under certain circumstances. In addition to the renin-angiotensin and arachidonic acid-prostanoid systems, the kallikrein-kinin system appears to modulate TGF activity. A large body of evidence indicates TGF activity is inversely correlated with renal interstitial pressure. Whether this correlation reflects causality or a phenomenological association awaits further investigation.