THE EFFECT OF EPINEPHRINE (USP), l-EPINEPHRINE, AND l-NOREPINEPHRINE ON GLOMERULAR FILTRATION RATE, RENAL PLASMA FLOW, AND THE URINARY EXCRETION OF SODIUM, POTASSIUM, AND WATER IN NORMAL MAN 12

There are marked hourly variations in the urinary output of sodium, chloride, and potassium in normal subjects. Some of these are clearly related to intake and others are produced by major physiologic adaptations, as changing from the supine to the erect position. However, considerable variations occur from day to day and hour to hour in the fasting supine subject. The purpose of this paper is to report the variations in excretion of Na, Cl, and K in normal subjects at rest and during motionless standing and compare them with the changes produced by cortisone and desoxycorticosterone glucoside (DCG), and after adrenal stimulation by corticotropin (ACTH). METHODSSodium and potassium in urine were measured by the flame photometer (1). Urinary chloride was measured by the silver iodate method (2).Normal healthy college students were used. For three days before the experiments, the subjects were on a low-sodium diet (less than 0.5 Gm. NaCI) and were given 3 Gm. of NaCl orally every three hours. This was a daily intake of 24.5 Gm. NaCl or 422 mEq. We hoped that this high intake of NaCl would inhibit the mechanism normally causing retention of NaCl and thus allow ACTH, cortisone and DCG to have maximum action on salt excretion.Except for water, ad lib., and 3 Gm. of NaCi every three hours, subjects were fasted for 12 hours before the experiment. In most instances, they slept in the laboratory on the night before the experiment. designed to measure the effect of ACTH, cortisone, DCG and tilting on the excretion of Na, Cl, and K. The excretion rates during the first and second hours were compared with the excretion rates for the first and second hours of the control group to be certain that comparable factors were acting during all sets of experiments. Two hours after the experiment started, ACTH, DCG and cortisone were given. In determining whether significant changes had occurred after the use of drugs, comparable hours were compared with those from the control series. RESULTSFasted subjects in bed without medication. Twelve experiments were run on five subjects. The hourly excretion (not recorded here) of Na, K, and Cl from 6:00 a.m. to 12:00 noon varied up and down from day to day and hour to hour in both the same and different subjects. There was no detectable correlation between the initial hourly excretion rate and the ratios Na/Cl, K/Cl, and K/Na. Over the six hours of the experiment, in spite of wide hourly variations, the quantities of Na, K, and Cl excreted progressively increased.The Na/Cl ratio showed little change. The K/Na and K/Cl ratios rose slightly in the first four hours as K excretion increased and then fell back toward the initial values as Na and Cl excretion continued to rise (data not recorded).Intravenous ACTH. Seven experiments were run on four subjects. ACTH (Wilson) was given intravenously in three minutes in doses of 20 units at 8:00 a.m. In the first two hours before ACTH, Na excretion was somewhat less than in the fasted group (p < .05). The excretion of K, Cl, and Na/Cl, K/Cl, and K/Na r...

Section: Resultsmentioning

confidence: 99%

Electrolyte Excretion After Single Doses of Acth, Cortisone, Desoxycorticosterone Glucoside, and Motionless Standing 123

Holland¹,

Stead²

1954

“…The possibility was also examined that changes in autonomic neural tone from arterial baroreceptors is responsible for suppression of ADH release with intravenous norepinephrine. In sham-operated animals intravenous norepinephrine diminished Uosm from 1,034 to 205 mosmol/kg H20 (P < 0.001) whereas in animals with denervated arterial baroreceptors intravenous norepinephrine was not associated with a significant alteration in Uosm (1,233 to 1,232 mosmol/kg) H20. These different effects on urinary osmolality occurred in the absence of differences in plasma osmolality and volume status.…”

mentioning

confidence: 86%

“…The effect of intravenous norepinephrine to increase renal water excretion has been well documented in both humans (1)(2)(3) and animals (4,5). Recent experimental evidence has demonstrated that this effect of norepinephrine is primarily related to its alpha adrenergic-stimulating properties (4,5).…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Suppression of Vasopressin during Alpha-Adrenergic Stimulation with Norepinephrine

Berl¹,

Cadnapaphornchai²,

Harbottle³

et al. 1974

A B S T R A C T Recent studies have demonstrated that the water diuresis associated with intravenous infusion of norepinephrine is mediated primarly by suppression of antidiuretic hormone (ADH) release. To investigate whether the increase in cerebral perfusion pressure with intravenous norepinephrine (0.5 jg/kg/min) is directly responsible for suppression of ADH release, the carotid circulation of dogs was pump-perfused bilaterally to selectively increase cerebral perfusion pressure. In six experiments cerebral perfusion pressure was increased from a mean of 125 to 151 mm Hg and then returned to 120 mm Hg. This maneuver was not associated with a reversible increase in renal water excretion. The possibility was also examined that norepinephrine exerts a direct central effect to suppress ADH release. In 12 experiments norepinephrine was infused into the carotid artery in a subpressor dose (0.12 ,tg/kg/min) estimated to equal the amount of the catecholamine reaching the cerebral circulation with intravenous norepinephrine. The urinary osmolality (Uosm) was not significantly altered with intracarotid norepinephrine (932 to 959 mosmol/kg H20. The possibility was also examined that changes in autonomic neural tone from arterial baroreceptors is responsible for suppression of ADH release with intravenous norepinephrine. In sham-operated animals intravenous norepinephrine diminished Uosm from 1,034 to 205 mosmol/kg H20 (P < 0.001) whereas in animals with denervated arterial baroreceptors intravenous norepinephrine was not associated with a significant alteration in Uosm (1,233 to 1,232 mosmol/kg) H20. These different effects on urinary osmolality occurred in the absence of differences in plasma osmolality and volume status. The results therefore indicate that norepinephrine primarily suppresses ADH release by altering autonomic baroreceptor tone rather than by a diReceived for publication 9 July 1973 and in revised form 29 August 1973. rect central or pressor effect of the catecholamine. This same mechanism may be the primary pathway for other nonosmotic influences on ADH release. INTRODUCTIONThe effect of intravenous norepinephrine to increase renal water excretion has been well documented in both humans (1-3) and animals (4, 5). Recent experimental evidence has demonstrated that this effect of norepinephrine is primarily related to its alpha adrenergic-stimulating properties (4,5). Moreover, studies from our laboratory have shown that this effect of norepinephrine on -renal water excretion is mediated primarily by suppression of vasopressin release rather than a direct effect

“…Sodium, potassium, and chloride excretion into urine and renal blood flow decrease (1,2). These effects are mediated by E stimulation of a,, a2, f1, and f2 receptors present in renal tissue (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Rat renal epinephrine synthesis.

Kennedy¹,

Elayan²

1989

Rats that underwent adrenal demedullation had a 93% decrease in plasma epinephrine (E) levels, but did not decrease their renal E. Even further treatment with 6-hydroxydopamine and reserpine failed to lower renal E levels. Similarly, urine E levels failed to decrease after adrenal demedullation and renal denervation. There is a renal E-synthesizing enzyme that differs from adrenal phenylethanolamine-N-methyltransferase (PNMT) in that it is only weakly inhibited by SKF 29661 and can synthesize epinine from dopamine, while adrenal PNMT does so poorly. When an adrenalectomized rat received intravenous IH]methionine, its urine contained radioactivity that appeared to be [HIE, with small amounts of[3Hepinine. However, after [Hjmethionine was infused in the renal artery, the major product in urine appeared to be I3Hjepinine, with a small amount of 13H]E. Adrenal demedullation induced renal E synthesis, but denervation returned the rate of renal E synthesis to control values. The combination of adrenal demedullation, 6-hydroxydopamine, and reserpine treatments increased renal E-forming activity to 350% of control.We conclude that appreciable portions of renal and urinary E are synthesized in the kidney by an enzyme distinct from PNMT. The enzyme is induced by some treatments that lower E and NE levels.