Evidence for increased renal norepinephrine overflow during sodium restriction in humans.

Abstract

To investigate the differentiated pattern of efferent sympathetic nerve activity by means of analyzing norepinephrine kinetics in response to sodium restriction, cardiorenal sympathetic activity during rest and mental stress was studied in 12 subjects (33.3 +/- 2.6 years old, SEM) exposed to a low and a normal sodium diet; 5-40 mmol and 160-200 mmol/24 hours, respectively (crossover design). Organ norepinephrine release was calculated from organ plasma flow, arteriovenous plasma concentration gradient across the organ and the organ's fractional extraction of radiolabeled norepinephrine. Body weight and urinary sodium/24 hr fell significantly and urinary potassium/24 hr and both supine and standing blood pressure remained unchanged. Total norepinephrine release to plasma and norepinephrine plasma clearance were similar in both phases (approximately 460 ng/min and 1.90 l/min, respectively). A 138% increase in renal norepinephrine overflow was observed during sodium restriction (from 112 to 267 ng/min, p less than 0.025), which was due to elevated renal vein norepinephrine (434 versus 290 pg/ml, p less than 0.01) because renal plasma flow and renal norepinephrine extraction were unaltered. Similarly, sodium restriction caused a 168% elevation of renal renin secretion (p less than 0.05). Resting cardiac norepinephrine spillover and cardiac norepinephrine reuptake were unchanged between the two salt phases. Total and cardiac norepinephrine release, supine blood pressure, and heart rate increased to about the same extent in response to mental testing regardless of salt phase. In conclusion, sodium restriction induced a differential and physiological increase in resting renal sympathetic nervous activity, leaving cardiac norepinephrine overflow unchanged. Cardiac norepinephrine uptake was normal, which further supports the concept of a true increase of efferent renal nerve activity.

Short- and Long-Term Neuroadrenergic Effects of Moderate Dietary Sodium Restriction in Essential Hypertension

“…Visceral districts are presumably involved because in our patients sodium restriction also increased plasma epinephrine, although less sustainedly than plasma norepinephrine, and a drastic reduction in sodium intake has been reported to cause in man an increase in renal norepinephrine spillover. 4 Whether the heart is also involved is impossible to conclude from our data, because, although sodium restriction is not accompanied by tachycardia, resting HR is a very insensitive marker of adrenergic drive. 32 Second, at variance from the baroreceptorsympathetic reflex, the moderate reduction in sodium intake used in the present study was not accompanied by any initial or later impairment of the baroreceptor-HR reflex.…”

“…[1][2][3][4][5][6] Evidence has also been provided that under this circumstance there can be an impairment in the baroreceptor modulation of vagal and sympathetic cardiovascular outflow, 6 -8 leading to a 2-fold conclusion. First, in hypertension, a marked reduction in dietary sodium content additionally enhances the sympathetic hyperactivity characterizing several patients with a high BP state, 5,9 -12 thereby aggravating its undesirable cardiovascular, metabolic, and hemorheologic effects.…”

Increased norepinephrine spillover into the jugular veins in essential hypertension.

“…This dose of desipramine has been previously determined to produce near maximal neuronal norepinephrine uptake blockade 23 while avoiding side effects such as nausea, which are sometimes seen with higher doses. Arterial and internal jugular venous blood samples were collected at rest and within 30 minutes of completing the infusion in these nine subjects for determination of brain and whole body norepinephrine spillover rates.…”

Sympathetic Nervous Activation in Essential Hypertension

“…This was surprising given the contrary effect on sympathetic tone seen with sodium depletion produced by either a diuretic 8 or dietary sodium restriction. 11 Brain mineralocorticoid receptors mediating excitation of central nervous system sympathetic outflow have been described 12 ; the effect of antagonizing these (lowered sympathetic tone) must have overridden any sympathetic stimulation from sodium depletion. Perhaps this sympathetic inhibition contributed to the blood pressure reduction being greater with spironolactone than hydrochlorothiazide in the study by Wray and Supiano.…”

“…Perhaps this sympathetic inhibition contributed to the blood pressure reduction being greater with spironolactone than hydrochlorothiazide in the study by Wray and Supiano. 10 The sympathetic activation from sodium depletion, which preferentially involves the renal sympathetic outflow, 11 is adaptive, promoting a counterbalancing renal retention of sodium. 6 Of the differing methods used for investigating the sympathetic nervous system in clinical research, each have strengths and weaknesses.…”