On the renal basis for essential hypertension: nephron heterogeneity with discordant renin secretion and sodium excretion causing a hypertensive vasoconstriction-volume relationship.
We propose herein that there are two functionally abnormal nephron populations in essential hypertension: (1) a group of ischemic nephrons with impaired sodium excretion which chronically hypersecrete renin. Numerically, these ischemic nephrons comprise a minor subgroup since most patients with essential hypertension exhibit no overt evidence of renal insufficiency. (2) In reaction to this, a more numerous group of normal nephrons appears in adaptive hypernatriuresis. They have an increased distal sodium supply and consequently, a chronically suppressed renin secretion. One difference between patients with renovascular hypertension and those with essential hypertension is the intermingling of these two populations of nephrons. In our hypothesis, the adapting hyperfiltering normal nephrons accomplish the hypernatriuresis in response to saline infusion, that is characteristic of all essential hypertension. However, the unsuppressed secretion of renin, that arises from the ischemic nephron population attenuates this compensatory natriuresis in the following ways: (1) by inappropriately acting on the hyperfiltering nephrons to enhance proximal tubular sodium reabsorption; (2) by activating TGF-mediated afferent constriction in these nephrons, and (3) simultaneously, the reactive secretion of renin from ischemic nephrons is diluted by non-participation of the adapting hypernatriuretic nephrons so that plasma renin settles at a level which is insufficient to fully compensate GFR in the ischemic nephrons. These adaptive responses provide a basis for the observation that the inhibition of renin activity with converting enzyme inhibitors in essential hypertension increases renal blood flow and sodium excretion. They also explain why converting enzyme inhibitors can effectively reduce blood pressure, even when renin levels are not absolutely elevated, since any circulating renin imposed upon the adapting hypernatriuretic nephrons inappropriately impairs their sodium excretion. In addition, the theory explains why basal renin secretion is either not suppressed or inadequately suppressed in patients with essential hypertension. As a result, whole kidney homeostatic function is compromised because individual nephrons are responding to their individual stimuli to fulfil their individual need, rather than acting in concert with other nephrons. The net effect of this uncoordinated response is to shift total renal function so that systemic arterial hypertension is sustained by abnormal sodium retention for the inappropriately high plasma renin level, or vice versa.(ABSTRACT TRUNCATED AT 400 WORDS)
Sealey
J E
JE
Cardiovascular Center, New York Hospital-Cornell Medical Center, New York, New York 10021.
Blumenfeld
J D
JD
Bell
G M
GM
Pecker
M S
MS
Sommers
S C
SC
Laragh
J H
JH
D006706:Homeostasis; D006801:Humans; D006973:Hypertension / Q000209:etiology*; D006978:Hypertension, Renovascular / Q000209:etiology; D008962:Models, Theoretical; D009318:Natriuresis; D009399:Nephrons / Q000503:physiopathology*; D011311:Pressoreceptors / Q000502:physiology; D012078:Renal Artery Obstruction / Q000150:complications; D012079:Renal Circulation; D012083:Renin / Q000378:metabolism*
D012083:Renin