On the renal basis for essential XXXX : nephron heterogeneity with discordant @entity916 secretion and @entity1372 excretion causing a hypertensive vasoconstriction-volume relationship.

@entity1 @entity101 @entity4295 @entity63 @entity73 @entity1372 @entity2792 @entity177 @entity916
We propose herein that there are two functionally abnormal nephron populations in essential @entity101 : (1) a group of @entity63 @entity4295 with impaired @entity1372 excretion which chronically hypersecrete @entity916 . Numerically, these @entity63 @entity4295 comprise a minor subgroup since most @entity1 with essential @entity101 exhibit no overt evidence of @entity177 . (2) In reaction to this, a more numerous group of normal @entity4295 appears in adaptive hypernatriuresis. They have an increased distal @entity1372 supply and consequently, a chronically suppressed @entity916 secretion. One difference between @entity1 with @entity2792 and those with essential @entity101 is the intermingling of these two populations of @entity4295 . In our hypothesis, the adapting hyperfiltering normal @entity4295 accomplish the hypernatriuresis in response to saline infusion, that is characteristic of all essential @entity101 . However, the unsuppressed secretion of @entity916 , that arises from the @entity63 nephron population attenuates this compensatory natriuresis in the following ways: (1) by inappropriately acting on the hyperfiltering @entity4295 to enhance proximal tubular @entity1372 reabsorption; (2) by activating TGF-mediated afferent constriction in these @entity4295 , and (3) simultaneously, the reactive secretion of @entity916 from @entity63 @entity4295 is diluted by non-participation of the adapting hypernatriuretic @entity4295 so that plasma @entity916 settles at a level which is insufficient to fully compensate GFR in the @entity63 @entity4295 . These adaptive responses provide a basis for the observation that the inhibition of @entity916 activity with converting enzyme inhibitors in essential @entity101 increases renal blood flow and @entity1372 excretion. They also explain why converting enzyme inhibitors can effectively reduce blood pressure, even when @entity916 levels are not absolutely elevated, since any circulating @entity916 imposed upon the adapting @entity73 their @entity1372 excretion. In addition, the theory explains why basal @entity916 secretion is either not suppressed or inadequately suppressed in @entity1 with essential @entity101 . As a result, whole kidney homeostatic function is compromised because individual @entity4295 are responding to their individual stimuli to fulfil their individual need, rather than acting in concert with other @entity4295 . The net effect of this uncoordinated response is to shift total renal function so that systemic arterial @entity101 is sustained by abnormal @entity1372 retention for the inappropriately high plasma @entity916 level, or vice versa.(ABSTRACT TRUNCATED AT 400 WORDS)
