Sympathetic nervous system and age-dependent salt hypertension in Brattleboro rats.

The effects of early sympathectomy on the development of salt hypertension were studied in prepubertal and adult rats with hereditary diabetes insipidus (DI). Early guanethidine administration caused a pronounced and long-term destruction of sympathetic nervous system (SNS) in Brattleboro rats in which blood pressure (BP) was significantly decreased until the age of 22 weeks. This SNS impairment did not abolish the age-dependent BP response of salt-loaded rats that was still greater in young than in adult sympathectomized DI rats. BP of young uninephrectomized DI rats was higher in the late than in the early phase of salt hypertension development. The early sympathectomy lowered BP and increased mortality in all groups of saline drinking DI rats except young uninephrectomized animals in which hypertensive response was attenuated but not prevented. It could be suggested that 1) increased BP response of young rats to high salt intake occurs even in animals with attenuated principal pressor systems, 2) the effects of early sympathectomy on the development of salt hypertension depend on the actual hemodynamic pattern, and 3) moderate BP increase might be a part of homeostatic mechanisms defending the organism threatened by chronic salt overload.

Effects of unilateral nephrectomy during early pregnancy.

Litter data and kidney growth parameters in Wistar rats uninephrectomized (UNX) or sham-operated (SO) on the 5th-7th day of gestation, and in unoperated controls (C) were investigated at 1 day and at 6 wk postpartum. Gestation period, litter size, sex ratio of pups, and pup weight at birth did not differ among the groups. At 6 wk, pups from UNX mothers displayed retarded growth. Compensatory kidney growth following UNX in pregnant rats was predictable for wet weight, but dry weight compensation was transient and limited.

Atrial natriuretic factor in taurine-treated normal and cardiomyopathic hamsters.

Diuretic and natriuretic activities of atrial extracts from BIO 14.6 (cardiomyopathic) and F1B (normal) hamsters at 180 days of age were measured by rat bioassay. Both activities were lower in BIO 14.6 extracts. Because of the reported protective action of taurine in the cardiomyopathic hamster, we tested the effect of 0.1 M taurine drinking upon the activity of atrial extracts. Urine flow and Na+ excretion were increased in both BIO 14.6 and F1B; however, comparatively larger increases in BIO 14.6 taurine drinkers abolished strain differences that were observed in water drinkers. Taurine drinking BIO 14.6 hamsters exhibited an increased plasma sodium concentration. Drinking of 0.6% NaCl also produced an elevated plasma sodium concentration in BIO 14.6. Extracts from hamsters with increased salt intake had diuretic and natriuretic activities that were not different from those of water drinkers. These findings confirm that ANF activity is deficient in BIO 14.6 hamsters, and this suggests a role for taurine in its production, release, and/or activation.

Comparison of soft tissue calcium levels throughout the life spans of normal and myopathic hamsters.

Comparisons of calcium levels in heart, skeletal muscle, brain, liver and plasma were made throughout the life spans of normal and genetically myopathic hamsters. A large calcium accumulation occurred in, and was restricted to, myopathic tissues (heart and skeletal muscle). Calcium elevation in myopathic tissues corresponded to documented lesion appearance, and persisted throughout the remainder of the life span. Calcium buildup in heart and skeletal muscle, as a central feature of the myopathic process, does not reflect a general failure of calcium homeostasis; nonmyopathic tissues are unaffected. Calcium increased moderately in some normal tissues late in life.

Endogenous vasopressin and the weaning period in Brattleboro rats.

Vasopressin, which is important for behavior and brain development, begins to influence osmoregulation with the onset of weaning. We studied the role of vasopressin in the development of feeding behavior since its mechanisms might be essential for the age determination of the suckling and weaning periods. Radionuclide methods were employed to follow maternal milk, solid food and water consumption in developing Brattleboro rats. The appearance of solid food intake and the spontaneous extinction of maternal milk intake indicated the onset and the end of weaning. The absence of endogenous vasopressin did not influence the onset and/or the duration of the weaning period. Both vasopressin-deficient homozygous Brattleboro rats and their heterozygous littermates (with preserved vasopressin synthesis) began to consume solid food and water at the age of 16 days and their intake of maternal milk was terminated about the 27th day of age. Thus, the maturation of feeding behavior in the suckling and weaning periods is vasopressin-independent.

Kidney growth and collagen content in rat pups from uninephrectomized mothers.

The effect of uninephrectomy (UNX) or sham-operation (SO) in pregnant rats at the 5th-7th day of gestation upon pup kidney development was studied. In newborns, kidney wet weight was low in pups of the SO and UNX groups, kidney/body weight was low in UNX only; collagen was highest in UNX. At 6 weeks, wet weight was least in UNX; dry weight was low and %H2O high in SO and UNX; collagen/dry weight was high in SO and UNX. Maternal surgery (SO or UNX) appears to impose a non specific development deficit upon pups, although kidney collagen growth is sustained; no specific renotropic activity was evident in pups of the UNX groups.

Taurine and ethanol-induced sleeping time in mice: route and time course effects.

Taurine was given to mice: (i) intracerebroventricularly (i.c.v.) 20 min prior to 4.5 g/kg of ethanol intraperitoneally (i.p.); (ii) i.p. 10 min-5 days prior to ethanol; or (iii) orally (p.o.) as drinking fluid for 30 days prior to ethanol. Ethanol-induced sleeping time was increased by i.c.v. taurine and also by i.p. taurine when the pretreatment interval was 4-5 days. The long i.p. pretreatment time probably reflects the slow uptake of taurine by the brain. Sleeping time was decreased by p.o. taurine and by i.p. taurine when the pretreatment interval was 10-20 min. The mechanism of this attenuation remains unclear.

Age-dependent differences in the effect of atrial natriuretic factor.

Replacement of drinking water by 1.8% NaCl solution produces a severe hypernatremia in prepubertal rats and only a moderate elevation of the plasma sodium concentration (pNa) in adults. Hypernatremia in prepubertal rats was reduced by infusion of blood from adult rats, whereas blood from young rats was without this effect. The aim of this study was to find out if the natriuretic factor containing atrial extracts from prepubertal (AEP) and adult (AEA) rats also differ in their ability to reduce hypernatremia in prepubertal rats. A decrease of pNa was observed 10 min after the administration of AEA (delta = -5.43 mmol/l). AEP failed to show this effect (delta = +0.92 mmol/l). No significant effect of AEA on pNa was observed in adult rats with moderate hypernatremia (delta = -1.88 mmol/l). Natriuretic and diuretic effects of AEP were also significantly lower than those of AEA if they were tested in prepubertal recipients, whereas no difference in activities of AEP and AEA was found in adult recipients. Possible mechanisms of the hypernatremia suppressing activity of AEA, causes of the differences in activities between AEA and AEP, and consequences of the low AEP activity for prepubertal rats are discussed.

Compensatory kidney collagen growth vs. age in uni-nephrectomized rats.

Kidney collagen content, wet and dry weights, were measured in male Wistar rats unilaterally nephrectomized (NX) at ages ranging from 3-52 weeks. The compensatory responses in the contralateral kidney were assessed at eight (NX + 8) and 16 (NX + 16) weeks post-operatively; the (NX) values were compared with those from sham-operated controls at the same age and post-operative time. Both (NX) and sham (S) values were contrasted to the normal kidney growth parameters of unoperated control (C) rats. Kidney wet weight in the (NX) group was greater than that in either (S) or (C) and the major part of the compensatory growth occurred in the (NX + 8) period. In younger rats (12 weeks at NX), the dry weight response was like that of net weight, but in older animals the dry weight compensation had a generally slower onset. The compensatory growth of collagen in younger (NX) rats was greater than that seen in (S), and (S) was the same as (C). In older rats, (NX) and (S) collagen were not different, but both were much higher than (C). The finding that older animals, unlike young ones, increase their kidney collagen in response to surgery, with or without a loss of renal tissue, points to a nonspecific stimulus for collagen growth and suggests that, in older rats, the turnover equilibrium of collagen is shifted toward synthesis under such conditions.

[The osmoregulating function of the kidney and activity of the loop of Henle in water rats, gerbils and Brattleboro rats]. / Osmoreguliruiushchaia funktsiia pochki i deiatel'nost' petel' Genle u vodianykh krys, peschanok i krys Brattleboro.

The concentration index U-P Osm in dehydration was 7.9 in gerbil, 2.7 in water rats and 1.7 in the Brattleboro homozygote rats. The sodium content in the kidney medullar substance of the animals under study correlated with the ability for creation of the high concentration gradient U-P Osm. The sodium excretion for 100 ml of filtrate, in maximal suppression with furosemide of the Cl- ions reabsorption in the large ascending parti of Henle's loop, was practically the same in all the rodents under study. This suggests that not only the amount of reabsorbed sodium but also the morpho-functional organization of the kidney medullar substance aiding to retainment of sodium, maintain the creation of high osmotic gradient.

Age-dependent salt hypertension in Brattleboro rats: a hemodynamic analysis.

The hemodynamic effects of 0.6% saline, consumed either from youth (4th week of age) or from adulthood (12th week of age), were studied in unanesthetized, unoperated, and uninephrectomized homozygous female Brattleboro rats. Long-term saline drinking induced a general decrease of blood pressure in unoperated rats which was more pronounced in rats drinking it from youth. The relation of low systemic resistance and high cardiac output (observed at the age of 10-15 weeks) to the high mortality of these rats was discussed. Two phases were recognized in the development of salt hypertension in uninephrectomized rats drinking saline from youth. The increased systemic resistance played a major role during the early phase (13-15 weeks), while changes of body fluids as well as altered arterial compliance contributed to the elevation of systolic blood pressure in the late phase of salt hypertension (20-30 weeks of age). In uninephrectomized rats drinking saline from adulthood, the late blood pressure response was only slightly attenuated in comparison with uninephrectomized rats drinking saline from youth. The absence of increased arterial rigidity in the former group was the only major hemodynamic difference between these two groups of uninephrectomized rats aged 20-30 weeks.

Hypertension in Brattleboro rats and the injurious influence of salt in youth.

The effect of long-term intake of 0.6% NaCl solution on survival of Brattleboro rats, both homozygous for diabetes insipidus (DI) and heterozygous (non-DI), was investigated. Studies included whether the survival of animals could be influenced a) by the age at which the high salt intake started (either from prepuberty, i.e. from the 4th week, or after sexual maturation, i.e. from the 12th week of age); b) by uninephrectomy (UNX) which elicited hypertension in DI rats drinking saline from youth. All non-DI and those DI rats that drank saline only from adulthood, survived for the whole duration of the experimental, i.e. 14 weeks. Only 43% of animals survived in the group of DI rats drinking saline from youth. This high mortality was reduced by UNX carried out either simultaneously or 8 weeks after the onset of saline drinking. DI rats consumed several times more saline than non-DI rats. Nevertheless, the consumption was greater in the low-mortality than in the high-mortality group. Salt intake was moderately lowered by UNX. Plasma Na+ concentration was higher in rats of the high-mortality group and it was not affected by UNX. In DI rats plasma volume was greater than in non-DI rats and its values in the low-mortality group exceeded those ones of the high-mortality group. It was decreased by UNX in the low-mortality group but this was not true for the high-mortality group. It is concluded that high mortality in DI rats consuming saline from prepuberty is abolished by the intervention producing hypertension. The role of hypertension in a protection against the toxic effects of salt is discussed.

The effect of vanadate on the electrogenic Na+/K+ pump, intracellular Na+ concentration and electrophysiological characteristics of mouse skeletal muscle fibre.

The present study reports a discrepancy between the effects of vanadate on the membrane Na+-K+-ATPase and the Na+/K+ pump of the skeletal muscle. Vanadate in concentration 4 X 10(-6) mol/l which is necessary to block the enzyme Na+-K+-ATPase activity of membrane fractions failed to inhibit the electrogenic Na+/K+ pump of intact muscle cells. The effect of vanadate on the electrophysiological parameters of the muscle fibre membrane required much higher vanadate levels, but again, Na+/K+ pump was still active. Vanadate in concentrations 4 X 10(-4) and 4 X 10(-5) mol/l depolarized the membrane potential and decreased the membrane resistance [apparently in consequence of enhanced passive membrane permeability for Na+ ions]. Action potentials and the electrical excitability of the muscle fibre membrane were reduced by these vanadate concentrations.

A specific enzyme is not necessary for vanadate-induced oxidation of NADH.

It has recently been found that ortho- or metavanadate can effectively block (Na+ + K+)ATPase and that it loses its blocking potency when reduced to the vanadyl (VO2+) ion. The question arose whether vanadate could be involved (reduced) in an NAD-linked enzymatic redox system of the cell. Here we have studied the effect of vanadate on malate dehydrogenase (MDH, EC1.1.1.37) catalysed oxidation of NADH during the formation of malate from oxalacetate in vitro. The MDH reaction was accelerated by vanadate, but we found thatr vanadate does not require the presence of any specific enzyme or substrate to mediate NADH oxidation.