Natriuresis induced by mild hypernatremia in humans.

Andersen LJ, Andersen JL, Pump B, Bie P. Source

Department of Medical Physiology, Panum Institute, University of Copenhagen, DK2200 Copenhagen, Denmark.

Abstract
The hypothesis that increases in plasma sodium induce natriuresis independently of changes in body fluid volume was tested in six slightly dehydrated seated subjects on controlled sodium intake (150 mmol/day). NaCl (3.85 mmol/kg) was infused intravenously over 90 min as isotonic (Iso) or as hypertonic saline (Hyper, 855 mmol/l). After Hyper, plasma sodium increased by 3% (142.0 +/- 0.6 to 146.2 +/- 0.5 mmol/l). During Iso a small decrease occurred (142.3 +/- 0.6 to 140.3 +/- 0.7 mmol/l). Iso increased estimates of plasma volume significantly more than Hyper. However, renal sodium excretion increased significantly more with Hyper (291 +/- 25 vs. 199 +/- 24 micromol/min). This excess was not mediated by arterial pressure, which actually decreased slightly. Creatinine clearance did not change measurably. Plasma renin activity, ANG II, and aldosterone decreased very similarly in Iso and Hyper. Plasma atrial natriuretic peptide remained unchanged, whereas plasma vasopressin increased with Hyper (1.4 +/- 0.4 to 3.1 +/0.5 pg/ml) and decreased (1.3 +/- 0.4 to 0.6 +/- 0.1 pg/ml) after Iso. In conclusion, the natriuretic response to Hyper was 50% larger than to Iso, indicating that renal sodium excretion may be determined partly by plasma sodium concentration. The mechanism is uncertain but appears independent of changes in blood pressure, glomerular filtration rate, the renin system, and atrial natriuretic peptide.
PMID: 12010758 [PubMed - indexed for MEDLINE]

Studies on the Mechanism of Hypernatriuresis in Essential Hypertension in Relation to Measurements of Plasma Renin Concentration, Body Fluid Compartments and Renal Function
M. A. D. H. Schalekamp, X. H. Krauss, M. P. A. Schalekamp Kuyken, G. Kolsters and W. H. Birkenhger Department of Internal Medicine, Zuiderziekenhuis, Rotterdam

Correspondence: Dr W. H. Birkenhger, Zuiderziekenhuis, Groeneveld 15, Rotterdam, Netherlands.

1. In twenty-two patients representing different stages of benign essential hypertension, hyperosmotic saline was administered intravenously. Determinations of intra-arterial pressure, renal plasma flow, glomerular filtration rate and plasma renin concentration were carried out before and, in the majority, also during and after saline infusion. Changes in cardiac output were followed in ten patients. Plasma volume and extracellular volume were determined in the control period only, although haemodilution was assessed by haematocrit readings. 2. Excess of sodium excretion showed a wide range and was related to the patient's age, as well as to a set of parameters reflecting intrarenal pressure patterns; hypernatriuresis consistently occurred in older patients, in whom renal vascular resistance and nitration fraction were elevated and plasma renin was suppressed. It could not be clarified whether hypernatriuresis together with renin suppression were determined by intrarenal pressure relationships or by an independent age-related factor in the hypertensive patient. 3. Excess of sodium excretion was not related to increments in arterial pressure, cardiac output, renal blood flow or glomerular filtration rate. 4. Plasma renin concentration failed to show consistent changes after hyperosmotic saline infusion. 5. It is concluded that natriuresis is not mediated by changes in the activity of the renin-angiotensin system. Hypernatriuresis appears to be a feature of progressive benign hypertension.

On the renal basis for essential hypertension: nephron heterogeneity with discordant renin secretion and sodium excretion causing a hypertensive vasoconstriction-volume relationship.
Sealey JE, Blumenfeld JD, Bell GM, Pecker MS, Sommers SC, Laragh JH. Source
Cardiovascular Center, New York Hospital-Cornell Medical Center, New York, New York 10021.

Abstract
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)