Peripheral flow response to transient arterial forearm occlusion does not reflect myocardial perfusion reserve.

BACKGROUND: Ultrasonographic evaluation of systemic arterial function is widely available, and a close relation of endothelial function in the coronary and brachial arteries has been documented. It is unknown, however, whether a similar correlation exists for their 2 microcirculatory territories and thus whether assessment of the systemic microcirculation can be used similarly as a surrogate marker of myocardial perfusion. METHODS AND RESULTS: Twenty-three patients with documented coronary artery disease (CAD; 66+/-9 years old, 18 men), 16 patients with syndrome X (SX; 56+/-5 years old, 13 women), and 45 healthy control subjects (C; 34+/-9 years old, 22 men) were studied. Myocardial perfusion was measured at rest and after dipyridamole (0.56 mg. kg(-1). min(-1) over 4 minutes) by PET, and brachial artery blood flow was measured at rest and after transient forearm ischemia by standard Doppler ultrasound techniques. Dipyridamole increased myocardial perfusion in all groups (mL. g(-1). min(-1): CAD, 0.89+/-0.27 versus 1.62+/-0.67, P:<0.001; SX, 0.82+/-0.16 versus 1.67+/-0.49, P:<0.001; and C, 0.82+/-0.15 versus 2.32+/-0.64, P:<0.001). Postocclusion forearm flow increased similarly in all groups (CAD, 52+/-18 versus 174+/-77 mL/min, P:<0.001; SX, 49+/-29 versus 202+/-82 mL/min, P:<0.001; and C, 61+/-34 versus 229+/-108 mL/min, P:<0.001). No significant correlations were found between peripheral and myocardial microcirculatory beds for either resting flow, hyperemic flow, or flow reserve in any of the groups (r(2)<0.1, P:=NS). CONCLUSIONS: The peripheral perfusion responses to transient forearm ischemia do not correlate with dipyridamole-induced myocardial hyperemia. The lack of correlation indicates different mechanisms of microvascular activation or regulation and confirms that extrapolations between findings in the 2 vascular beds are not suitable.

IGF, type I IGF receptor and IGF-binding protein mRNA expression in kidney and liver of potassium-depleted and normal rats infused with IGF-I.

Dietary potassium (K) depletion is known to reduce body weight gain and organ growth, except for kidney which increases in weight. This renal hypertrophy is preceded by increased renal IGF-I levels. In the present study, we investigated IGF-I and -II, type I IGF receptor and IGF-binding protein (IGFBP) mRNA expression in liver and kidney of K-depleted and normal rats infused with vehicle or recombinant human IGF-I. Body weight gain was almost completely arrested in K-depleted rats without any stimulatory effect of IGF-I infusion. Both absolute and relative kidney weight (kidney weight/body weight) were significantly increased in K-depleted rats and this was further enhanced by IGF-I infusion. In contrast, relative liver weight was comparable in the different groups and unaffected by IGF-I infusion. IGF-I mRNA expression was significantly lower in kidney and liver of K-depleted animals whereas type I IGF receptor levels were unchanged. In contrast, in kidney, K depletion increased IGFBP-1 and -2 mRNA expression with no additional effect of IGF-I infusion. In liver of K-depleted animals, IGFBP-1 mRNA expression was increased whereas increased IGFBP-1 and -2 mRNA expression was observed when these animals were infused with IGF-I. These observations may point towards a differential mode of action of the IGFBPs. In kidney increased IGFBP-1 and -2 mRNA expression may enhance IGF-I bioavailability with subsequent kidney growth. In liver, with clearly detectable type I IGF receptor mRNA expression, increased IGFBP levels may protect from IGF-I-induced organ growth by decreasing IGF-I bioavailability.

Effects of adrenal steroids on the concentration of Na(+)-K+ pumps in rat skeletal muscle.

Since adrenal steroids have been shown to upregulate the concentration of Na(+)-K(+)-ATPase in cardiac muscle, similar effects could be expected in skeletal muscle. Following infusion of dexamethasone (0.02-0.1 mg/kg per day) for 7 days in 10-week-old rats, the total concentration of [3H]ouabain-binding sites rose by up to 22-42% in soleus, extensor digitorum longus, gastrocnemius and diaphragm muscle. Dexamethasone produced no or minute changes in the Na(+)-K+ contents of skeletal muscle. In contrast, infusion with aldosterone (0.02-0.5 mg/kg per day) for 7 days produced hypokalemia and a graded reduction in the K+ content of skeletal muscle, which was closely correlated to a downregulation of the [3H]ouabain-binding site concentration (r = 0.65-0.70; P < 0.001). The results indicate that in skeletal muscle high doses of glucocorticoids upregulate the concentration of Na(+)-K+ pumps whereas mineralocorticoids induce a downregulation, which is secondary to the concomitant K+ deficiency. Since adrenalectomy produced no significant change in [3H]ouabain-binding site concentration, basal levels of endogenous adrenal steroids seem to be of minor importance for the regulation of Na(+)-K+ pump concentration in skeletal muscle.

Growth hormone (GH) receptor and GH-binding protein deficiency in the growth failure of potassium-depleted rats.

Potassium (K+) deficiency is associated with growth retardation in both man and experimental animals. Growth hormone (GH) administration to such animals prevents, to some extent, weight loss and selective muscle atrophy, but does not affect tail and tibia length even with supraphysiological doses. The present study was undertaken to investigate the possible effect of K+ deficiency on the hepatic GH receptor and GH-binding protein (BP). Young female Wistar rats were maintained on K(+)-deficient fodder and distilled water, and compared with pair-fed and ad-libitum-fed control groups. After 15 days GH-BP and electrolytes were measured in sera, GH receptors were studied in liver membranes by 125I-labeled human GH binding and muscles were weighed and saved for electrolyte measurements. K(+)-deficient rats showed complete growth arrest compared with an intermediate weight gain of the pair-fed group. Serum K+ was very low, at 1.5 +/- 0.1 mmol/l, compared with the mean value of 5.3 mmol/l of control animals. Somatogenic and lactogenic receptors in liver membranes and serum GH-BP levels were significantly (P < 0.05) lower in K+ deficiency, as compared with their pair-fed controls. Liver GH receptors correlated significantly (P < 0.05) with serum GH-BP levels. The growth variables correlated positively with both hepatic somatogenic and lactogenic receptors and serum GH-BP levels, with correlation coefficients that were highest against serum GH-BP and lowest against liver lactogenic receptors. Serum and muscle K+ correlated significantly (P < 0.05) with both liver GH receptors and serum GH-BP, with correlation coefficients that were higher against serum GH-BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence that potassium deficiency induces growth retardation through reduced circulating levels of growth hormone and insulin-like growth factor I.

Growth retardation and impaired protein synthesis are major characteristics of potassium (K)-deficiency in animals and man. We have evaluated the effect of K-deficiency on growth, serum growth hormone (s-GH), insulin-like growth factor I (s-IGF-I), and insulin (s-insulin) in young rats. After 10 days on K-deficient fodder, 4 1/2-week-old rats showed a 54% reduction in serum potassium (s-K) and a weight gain that was reduced by 97%, compared with pair-fed controls. In addition, tail length, tibia length, and muscle weight of soleus in K-depleted animals were all significantly reduced compared with pair-fed controls. The growth retardation was accompanied by a 46% reduction in s-IGF-I, while s-insulin showed no decrease. K-repletion in animals depleted for 7 days showed complete normalization of s-K within 24 hours, in addition to a significant increase in both s-IGF-I and weight. In 4-week-old rats maintained on K-deficient fodder with variable K-content (1 to 260 mmol/kg) for 1 week, a strong correlation between the K-content of fodder and s-IGF-I could be established (r = .88, P less than .001), as well as between s-IGF-I and weight gain (r = .90, P less than .001). Furthermore, a stepwise reduction in basal s-GH was seen with the graded reduction of dietary K-content.(ABSTRACT TRUNCATED AT 250 WORDS)

[Magnesium and long-term diuretic therapy]. / Magnesium og langvarig diuretikabehandling.

Thiazides and loop diuretics, facilitate the loss of Mg and K resulting in increased excretion in the urine. Although serum-K and serum-Mg values in patients receiving long-term treatment for hypertension or incompensated heart disease usually are normal, muscle-Mg and muscle-K contents are reduced in around 50% of these patients. Mg deficiency increases K loss and K/Mg deficiencies are frequently observed simultaneously. K repletion is often difficult if the accompanying Mg deficiency is not corrected simultaneously. The K/Mg loss from the muscles is accompanied by reduced concentration of Na,K-pumps. These disturbances may produce muscle symptoms, increased sensitivity to digitalis, inhibition of growth and possibly arrhythmias. Evaluation of the K and Mg status during diuretic treatment should be preferentially based on tissue determinations. The muscle biopsy method is rapid, reliable and may reveal conditions of deficiency. In several cases, oral supplements of Mg have proved to be adequate to restore the normal K/Mg status.

[Complications caused by intrauterine contraceptive devices]. / Komplikationer ved kontraception med intrauterin spiral.

During the period 1981-1982, IUDs were introduced in 1,697 women in the Advisory Clinic for Contraception in the County of Arhus. The course in a period of six years after this was investigated retrospectively in view of the frequencies of complications. A total of 459 IUDs were either lost or had to be removed on account of haemorrhage/pain, infection or pregnancy. Where all types of complications were concerned, higher frequencies of complications were encountered in the younger age groups and in nulliparous women. The dependence of the frequency of complications on the age of the patients was most marked among women who had borne children previously. In the total population, 29% of the women had the IUD removed within a period of three years. In women under the age of 20 years, 45% were removed and, in women over the age of 35 years, only 18% were removed during the same period. The total pregnancy risk was 2.7/100 women after use for two years and 3.2/100 women after three years. In contrast to this, the risk in women under 20 years was 6.6/100 women and 10.8/100 women after use for two and three years, respectively. On account of a high frequency of infection, increased tendency to extrusion and poor effectivity, the use of IUDs in young nulliparous women is not recommended.

PIP: Between 1981-82, IUDs were introduced in 1697 women in the Advisory Clinic for Contraception in the County of Arhus. What followed over the next 6 years was a retrospective investigation of the complications which resulted. A total of 459 IUDs were either lost or has to be removed due to hemorrhage, pain, infection, or pregnancy. Where all types of complications were concerned, higher frequencies of complications occurred in those in younger age groups and among nulliparous women. The dependence of frequency of complications on the age of the patient was most marked among women who had had children previously. In the total population, 29% of the women had their IUDs removed within a period of 3 years. In women under age 20, 45% were removed and in women over 35, only 18% were removed during the same period. The total pregnancy risk was 2.7/100 women after 2 years of use and 3.2/100 women after 3 years of use. In contrast, the risk in women under age 20 was 6.6/100 women and 10.8/100 women after use between 2 and 3 years, respectively. Due to the high frequency of infection, increased tendency to extrusion, and poor efficacy, the use of IUDs in young, nulliparous women is not recommended. (author's modified)

[Non-invasive assessment of endothelial function]. / Ikkeinvasiv vurdering af endotelfunktionen.

Endothelial dysfunction is an early event in atherosclerosis preceding the formation of plaques. An important functional consequence of endothelial damage is reduced vasodilatory responses to a variety of pharmacological and physiological stimuli including reactive hyperaemia. Hitherto, endothelial function could only be assessed by invasive techniques, but a novel ultrasound based technique has recently been developed, which allows non-invasive evaluation of endothelial function in large systemic arteries such as the brachial artery. The technique is accurate, reproducible and able to differentiate between subjects with and without vascular dysfunction. Impaired endothelial function has been documented in young and adult individuals with various vascular risk factors including cigarette smoking, diabetes mellitus, hypercholesterolaemia, and homocystinuria. A good correlation has been found between both the presence of atherosclerotic lesions and endothelial function in the coronary arteries and the brachial artery. The method may help in identification of individuals with early vascular changes and thereby make risk factor modification possible at a very early stage of the atherosclerotic process. It may furthermore serve as a tool to monitor the impact of prevention and intervention on arterial damage.

[Increased concentration of Na,K-pumps in skeletal muscles of patients with chronic obstructive lung disease. Significance of magnesium depletion and treatment with glucocorticoids]. / Forøget koncentration af Na,K-pumper i tvaerstribet muskulatur hos patienter med kronisk obstruktiv lungesygdom. Betydning af magnesiumdepletering og behandling med glukokortikoider.

Patients with COLD may develop Mg depletion due to inadequate nutrition or treatment with diuretics and beta 2-agonists. In 36 consecutive COLD patients skeletal muscle concentrations of Mg and K were reduced by 22% and 14%, respectively, compared to 23 age- and sex-matched controls (p < 0.001). Patients receiving diuretics showed a further reduction of muscle Mg (-31%) and K (-27%) compared to controls. The mean concentration of Na,K pumps was increased by 31% (p < 0.001), while a more pronounced increase (+61%) was seen in 12 intensive care patients receiving high dosages of glucocorticoids. Thus muscle concentrations of Mg and K are reduced in COLD patients and are associated with an upregulation of the Na,K-pump concentration. It is plausible that this upregulation may be caused by glucocorticoid treatment. The clinical benefits of glucocorticoids may therefore in part be due to an increased activity and capacity of the Na,K-pump and thereby in a possible enhancement of muscle force.

[Balloon dilatation of congenital aortic stenosis]. / Ballondilatation af medfødt aortastenose.

We evaluated the catheterization results and follow-up echocardiographic data in all (n = 31) patients undergoing balloon dilatation for congenital aortic valve stenosis at Skejby University Hospital from May 1987 to October 1996. Patients were between three weeks and 35 years of age (median 12.1 years). Peak-to-peak systolic pressure gradient was reduced by 59%, from 74 +/- 17 to 30 +/- 20 mmHg (p < 0.0001). Balloon valvuloplasty was successful in 26 (84%) patients. At follow-up 38 +/- 33 months after balloon valvuloplasty, 19 of these 26 patients (73%) had a persistent reduction in gradient compared with that before valvuloplasty. In the seven patients who had been operated during the follow-up period, balloon valvuloplasty had delayed surgical intervention by 6-97 (median 38) months. Balloon valvuloplasty is an effective, low risk palliative procedure in patients with congenital aortic valve stenosis.

[Oral magnesium supplementation to patients receiving diuretics--normalization of magnesium, potassium and sodium, and potassium pumps in the skeletal muscles]. / Peroralt magnesiumtilskud til patienter i diuretisk behandling--normalisering of magnesium, kalium og natrium, kalium-pumper i tvoerstribet muskulatur.

In 76 consecutive patients who had received diuretics for 1-17 years for arterial hypertension or congestive heart failure, muscle concentrations of magnesium, potassium, and sodium-potassium pumps were significantly reduced compared to 31 age- and sex-matched controls. Thirty-six patients with muscle magnesium and/or potassium below the control level received oral magnesium hydroxide supplement for 2-12 weeks (N = 20) or 26 weeks (N = 16). After short term (2-12 weeks) magnesium supplementation muscle parameters were increased, but far from normalized. After magnesium supplementation for 26 weeks, the muscle concentrations of magnesium, potassium and sodium-potassium pumps were normalized in most cases. Oral magnesium supplementation may restore diuretic-induced disturbances in the concentrations of magnesium, potassium and sodium-potassium pumps in skeletal muscle. A supplemental period of at least six months seems required before complete normalization can be expected.

Effects of K+, Mg2+ deficiency and adrenal steroids on Na+, K(+)-pump concentration in skeletal muscle.

Animal studies have shown that deficiency of K+ is associated with a reduction in the concentration of Na+, K+ pumps in skeletal muscle, and that this reduction is closely correlated with the reduction in the muscle K+ concentration. Furthermore, animals deficient in Mg+ show a downregulation of the Na+, K(+)-pump concentration, but this seems to be secondary to the concomitant K+ deficiency, which often accompanies Mg2+ deficiency. Measurements on skeletal muscle biopsies from patients who had been in long-term treatment with diuretics showed that 55% had reduced concentrations of both K+ and Mg2+, and that this was associated with a reduction in the concentration of Na+, K+ pumps. Furthermore, the Na+, K(+)-pump concentration correlated significantly with both muscle K+ and Mg2+, suggesting that the downregulation of the Na+, K+ pumps was related to the loss of K+, as predicted from the animal experiments. In accordance with this, normalization of muscle K+ and Mg2+ in response to oral Mg2+ supplementation, resulted in a restoration of the Na+, K+ pumps. Apart from thyroid hormone, which is another major regulator for the Na+, K(+)-pump concentration, other hormones may be of importance. It is well known that adrenal steroids control the synthesis of Na+, K+ pumps in the kidney and heart. Recently, treatment with dexamethasone was found to increase the Na+, K(+)-pump concentration in rat skeletal muscle. The increase was found in EDL, soleus, gastrocnemius and diaphragm muscles, and amounted to 23-52%. In contrast, treatment with aldosterone induced a decrease in the Na+, K(+)-pump concentration, which was closely correlated to the reduced K+ content of the muscles. The results indicate that in skeletal muscle, high doses of glucocorticoids upregulate the concentration of Na+, K+ pumps, whereas mineralocorticoids induce a downregulation which is secondary to the concomitant K+ deficiency.

Magnesium and potassium deficiency. Its diagnosis, occurrence and treatment in diuretic therapy and its consequences for growth, protein synthesis and growth factors.

Thiazides and loop diuretics facilitate the loss of K and Mg through the kidneys leading to deficiencies that may require treatment with supplements. These losses may be overlooked, however, because serum concentrations may remain normal even when the muscle concentrations are appreciably reduced. In 76 patients who had received diuretics for 1-17 years, the mean concentrations of K, Mg and Na,K-pumps in skeletal muscle biopsies were significantly lower than in those from an age- and sexmatched control group, and muscle Mg and K concentrations were significantly correlated. The serum concentrations, however, were only below the control range in a few patients. The fact that Mg,K deficiencies may often be overlooked emphasises the need for data on the contents of skeletal muscle. A recently developed simple biopsy needle procedure permitted the detection of disorders of electrolytes during long-term diuretic treatment despite normal serum concentrations. With the same technique it was possible to detect repletion of the muscle electrolytes after a Mg supplementation period. Oral Mg supplementation could reestablish normal Mg as well as K status in patients in long-term diuretic therapy, provided that the supplementation was maintained for 6 months. Moreover, the normalization of muscle Mg and K was accompanied by a restoration of the concentration of Na,K-pumps measured as the [3H]ouabain binding site capacity in skeletal muscle. Mg and K contents were closely correlated in human muscle biopsies from patients on diuretic treatment, but also in rat muscle which had been moderately Mg depleted in vivo or in vitro. In isolated soleus muscle, which had been moderately Mg-depleted in vitro, reduction in cellular K could not be ascribed to reduced Na,K-pump mediated K-influx. The reduced K content might rather be related to increased K efflux from the muscles. In rats, insufficient dietary supplies of K, Mg and Zn were characterized by inhibition of growth and protein synthesis. These effects could not readily be related to the loss of these elements from muscle tissue, but rather should be seen as a response to a general deficiency. The most marked evidence of deficiency was seen in the serum levels, which pointed to the serum concentration as a possible mediator for the regulation of tissue growth. IGF-I is a low molecular weight peptide possessing growth promoting properties in many tissues probably as an interplay of both autocrine/paracrine and endocrine actions. In both animals and man insufficient supplies of energy and protein are accompanied by growth retardation and a decrease in serum IGF-I.(ABSTRACT TRUNCATED AT 400 WORDS)

Characterization of bumetanide-sensitive Na+ and K+ transport in rat skeletal muscle.

In isolated rat soleus muscle an average of 23% of the total 22Na influx was found to be suppressible by bumetanide (K0.5 = 0.1 mM) and furosemide (K0.5 = 1 mM), whereas the influx and efflux of 42K were not affected. In extensor digitorum longus muscle, around 25% of the total 22Na influx was suppressible by bumetanide (1 mM). In the presence of ouabain, both diuretics decreased net intracellular accumulation of Na+, but caused no change in K+ content. In extensor digitorum longus (but not in soleus), bumetanide-suppressible 22Na influx was stimulated by increasing extracellular osmolarity with the bumetanide having no effect on 42K influx. Bumetanide-suppressible Na+ influx was almost abolished in Cl(-)-free buffer, but was unaffected by the omission of K+. In rat soleus, the inhibitory effects of bumetanide, amiloride and tetrodotoxin on 22Na influx were found to be additive. The results indicate that a NaCl cotransport system is present in both fast- and slow-twitch skeletal muscles, and may participate in volume regulation. Due to the large pool of muscle cells, activation of NaKCl2 cotransport is likely to entail the hazards of hypokalemia. The advantage of exerting volume control via NaCl cotransport is that this risk can be avoided.

Micronutrients, minerals and growth control.

(1) Dietary deficiencies of Zn, Mg and K lead to a rapid drop in serum concentrations, with no change (Zn) or a slow decline (Mg and K) in the concentrations in skeletal muscle. (2) These deficiencies all lead to inhibition of growth and protein synthesis in muscle. (3) The inhibition of protein synthesis is faster in onset than the loss of Zn, Mg and K from muscle and therefore unlikely to result from cellular mineral deficiency. (4) The deficiencies are likely to be detected by the early drop in serum concentration, but the mechanism is unknown. (5) Possible mediators of growth inhibition are anorexia, GH and IGF-I. (6) Early detection of mineral deficiencies allows the organism to minimize wasteful protein synthesis and the formation of functionally inadequate tissues.

Effects of magnesium and zinc deficiencies on growth and protein synthesis in skeletal muscle and the heart.

The effects of magnesium or zinc deficiency on growth, tissue contents of Mg or Zn and protein synthesis have been compared in 4-13-week-old rats. When maintained on Mg-deficient fodder (1.6 mmol/kg) or Zn-deficient fodder (27 mumol/kg) rats showed a reduced weight gain, whereas repletion caused increased growth rates. Pair-feeding experiments showed that this could not be attributed to reduced energy intake only. In rats maintained on Mg-deficient fodder for 14 d [3H] leucine incorporation into skeletal muscle and the heart was reduced by 24-38% compared with pair-fed controls (P less than 0.001-0.002). The incorporation of [3H]phenylalanine was reduced by 19-31%. Tissue Mg contents, however, were only reduced by 6-7% (not significant). The pair-fed rats showed no reduction in the [3H]leucine incorporation compared with ad lib.-fed animals. In rats maintained on Zn-deficient fodder for 15 d [3H]leucine incorporation into skeletal and heart muscle was reduced by 57-64% compared with pair-fed controls. The pair-fed rats showed no reduction in the [3H]leucine incorporation compared with ad lib. fed animals. In the Zn-deficient animals the content of Zn was not reduced in the skeletal muscles, whereas there was a small (15%) but significant loss of Zn in the heart. In another experiment, Zn depletion for 17 d caused a reduction in [3H]leucine incorporation of 35-41%. After 5 d of Zn repletion this defect was restored, and the [3H]leucine incorporation was above control level in the skeletal muscles. It is concluded that the intact organism is very sensitive to dietary Mg or Zn deficiency, and that the reduced growth and protein synthesis cannot easily be attributed to the reduction of tissue Mg or Zn content per se. This points to the existence of other control mechanisms mediating down-regulation of growth and protein synthesis in response to reduced dietary supplies and the ensuing drop in the plasma concentrations of Mg and Zn.

86Rb is not a reliable tracer for potassium in skeletal muscle.

For technical reasons, 86Rb is frequently preferred to 42K as a tracer for K+. Systematic comparisons of the two isotopes, however, are rarely done. In this paper we compare the transport of 42K and 86Rb in rat and mouse soleus muscle and in rat erythrocytes. Ouabain-suppressible K+ uptake in rat soleus was the same whether measured with 42K or 86Rb, both when stimulated by insulin, salbutamol and calcitonin-gene-related peptide (CGRP), and when inhibited by graded concentrations of ouabain. Control experiments with rat erythrocytes, where Na(+)-K(+)-Cl- co-transport has earlier been demonstrated, showed closely similar inhibitory effects of bumetanide on 42K and 86Rb uptake. In contrast, bumetanide produced no significant change in 42K uptake of rat and mouse soleus muscle, but clearly inhibited 86Rb uptake at concentrations down to 10(-7) M (P < 0.001). Whereas the addition of 150 mM NaCl had no effect on 42K uptake in rat soleus, 86Rb uptake, and in particular the bumetanide-suppressible component, was markedly increased by this addition. The inhibitory effect of bumetanide on 86Rb uptake gives rise to the false impression that skeletal muscle contains a NaKCl2 co-transport system. Efflux studies showed that the fractional loss of 42K from rat soleus muscle is 2.3 times larger than that of 86Rb. Salbutamol and CGRP increased 86Rb efflux, but inhibited 42K efflux. This implies that for studies of K+ efflux and bumetanide-sensitive K+ transport, 86Rb is not even an acceptable tracer for the detection of qualitative changes. Control experiments with 42K are essential in any characterization of unknown K+ transport processes.

Effects of IGF-I infusion on growth and muscle Na(+)-K+ pump concentration in K(+)-deficient rats.

K(+)-deficient rats and control rats were infused for 14 days with vehicle: acetic acid (AcA) or recombinant human insulin-like growth factor-I (IGF-I, 240 micrograms/day) by osmotic minipumps. IGF-I treatment of K(+)-deficient rats did not result in overall growth of carcass or muscles but in marked selective growth of adrenals (+42%) and spleen (+66%). In control rats, IGF-I induced increased body and muscle weight, tibia length, and thymus weight. K+ deficiency was associated with reduced serum IGF-I but unchanged thyroid status. IGF-I treatment of the K(+)-deficient rats restored serum IGF-I and decreased total 3,5,3'-triiodothyronine. In AcA-treated K(+)-deficient rats [3H]ouabain binding site concentration decreased by 63 and 43% in soleus and extensor digitorum longus (EDL) muscle, respectively, compared with the AcA-treated controls. IGF-I had no effect on the [3H]ouabain binding site concentration in the control group, but in K(+)-deficient rats a significant lowering of 26% was observed in EDL. K+ deficiency causes relative organ-specific resistance to the growth-promoting effects of IGF-I, comparable to the effects seen in protein-restricted rats. Reduced circulating IGF-I is not the only cause of the downregulation of Na(+)-K+ pumps in K+ deficiency, and IGF-I treatment of control animals in vivo has no stimulatory effect on the synthesis of Na(+)-K+ pumps.