Evidence of abnormalities in corticosteroid secretion leading to volume-dependent hypertension in Milan rats.

We examined corticosteroid secretory patterns and their relation to altered salt and water metabolism in Milan hypertensive and normotensive rats. Hypertensive rats had significantly higher blood pressures, exchangeable sodium (hypertensive, 41.2 +/- 0.3 mmol.kg-1; normotensive, 38.4 +/- 0.03 mmol.kg-1, P < .001), plasma volume (hypertensive, 5.39 +/- 0.12 mL.100 g-1; normotensive, 4.84 +/- 0.10 mL.100 g-1, P < .001), and plasma concentrations of atrial natriuretic peptide (hypertensive, 38.8 +/- 4.0 pg.mL-1, normotensive, 22.4 +/- 3.1 pg.mL-1, P < .02). These features coincide with those of mineralocorticoid-induced hypertension. Adrenal venous secretory rates (picomoles per minute) of corticosterone (hypertensive, 1696 +/- 202; normotensive, 873 +/- 139), 18-hydroxycorticosterone (hypertensive, 49.7 +/- 8.3; normotensive, 25.7 +/- 3.3), and aldosterone (hypertensive, 1.16 +/- 0.17; normotensive, 0.52 +/- 0.08) were higher in the hypertensive than the normotensive strain, but that of 11-deoxycorticosterone (DOC) (hypertensive, 94.4 +/- 14.9; normotensive, 114.3 +/- 33.9) was similar in the two strains. The corticosterone-DOC, 18-hydroxycorticosterone-DOC, and aldosterone-DOC ratios were higher in the hypertensive than the normotensive strain (P < .02), but the 18-hydroxycorticosterone-corticosterone and aldosterone-18-hydroxycorticosterone ratios were not. These results indicate increased activity of the "late" aldosterone biosynthetic pathway in the hypertensive compared with the normotensive strain caused by an increased conversion rate of DOC to corticosterone. The comparison of corticosterone secretion between the two strains indicates that 11 beta-hydroxylase rather than aldosterone synthase activity is more active in the hypertensive than the normotensive rats.

Effects of dexamethasone on body fluid and electrolyte composition of rats.

Low-dose infusions of dexamethasone (2 micrograms/day for 2 and 4 weeks) increased systolic blood pressure and decreased body weight gain in male rats. Total body sodium, calcium and magnesium were increased by dexamethasone treatment; potassium was unaffected. These changes have been evaluated bearing in mind that glucocorticoids have profound catabolic effects. Relative to pretreatment values, dexamethasone decreased exchangeable body sodium for the first two weeks of treatment although values were not significantly different from vehicle-treated controls. Hematocrit, plasma cholesterol and transaminase activities were increased by dexamethasone; white cell numbers and plasma volumes were decreased; plasma Na+, K+ and Ca2+, red cell numbers, extracellular fluid volume, and glomerular filtration rate were not significantly affected. It is concluded that glucocorticoids cause plasma volume to contract, possibly as a result of glucocorticoid-induced natriuresis. Any effects of dexamethasone on whole-body ionic composition are obscured by simultaneous changes of intermediary metabolism.

Effect of metoprolol on serial measurements of exchangeable sodium, blood pressure, renin and pulse rate in spontaneously hypertensive rats.

The cardioselective beta-blocker metoprolol was mixed with the diet (6 mg metoprolol/g food) and given to 9 spontaneously hypertensive rats (SHR) for four weeks, while 9 other SHR were given the plain diet only and served as controls. All rats were also given 0.5% drinking saline labeled with isotope 22Na (37 kBq/1) to drink. Measurements of total exchangeable sodium, blood pressure, pulse rate and weight were performed before and repeatedly during treatment. Plasma renin activity was measured at the end of the study. Before treatment exchangeable sodium, blood pressure, pulse rate and weight were no different between the groups. Metoprolol reduced the pulse rate and prevented the usual blood pressure increase in SHR. Both groups gained weight similarly. Exchangeable sodium increased similarly in both groups along with the weight increase. Plasma renin activity was not significantly different in the two groups. Thus, chronic metoprolol treatment of SHR reduced blood pressure and pulse rate in SHR but did not lower plasma renin or cause measurable sodium or fluid retention.

Acinetobacter calcoaceticus foot infection secondary to high-pressure injection injury: a case report.

Injection injuries are surgical emergencies occurring most often in the hand and frequently associated with widespread tissue necrosis and infection. This report presents a case of high-pressure injection injury of the foot associated with extensor hallucis longus laceration and infection with Acinetobacter calcoaceticus variant anitratus. This injury occurred with a high-pressure "water-blaster" tool used to remove paint from pavement. Similar injuries in the foot have not been reported. A. calcoaceticus is a widely distributed normal flora of low virulence, often waterborne, which is rarely found in orthopaedic infections in young healthy patients. Clinical features of high-pressure injection injuries, principles of treatment, and the characteristics of A. calcoaceticus are reviewed.

Dietary sodium deprivation raises blood pressure in the rat but does not produce irreversible hyperaldosteronism.

It is reported that dietary deprivation of sodium in young rats produces changes of sodium balance and aldosterone excretion which persist when normal sodium intake is restored. To test this further, sodium intake was reduced 10-fold in rats. In the first experiment sodium intake was reduced for 5 weeks in rats aged 3 weeks. Systolic blood pressure, heart rate and plasma renin concentration increased and growth rate was reduced. Sodium intake was then increased for 10 weeks. Blood pressure, heart rate and plasma renin concentration fell and growth rate increased but body weight did not regain control values. As compared with controls, plasma concentrations of aldosterone and corticosterone did not increase after the 10-week period. Thus, sodium depletion did not produce an irreversible change in aldosterone but it did raise arterial pressure. Further experiments confirmed the pressor effect in young and adult rats. Blood pressure was measured in the tail in these experiments but the increase in pressure was not a technical artifact as measurements made in the tail correlated well with measurements made simultaneously by intra-arterial catheter. Catheters were inserted under general anaesthetic for this comparison of pressure and rats previously deprived of sodium showed a significantly higher mortality rate due to the anaesthesia and surgery involved. Thus, a 10-fold reduction of dietary sodium raises blood pressure in young and adult rats and it may increase mortality from a minor surgical procedure. It does not produce irreversible changes in aldosterone.

Effect of nitrendipine on blood pressure, plasma renin, and exchangeable sodium in DOC-salt hypertension in the rat.

Desoxycorticosterone-salt (DOC-salt) hypertension in the rat can be prevented by administration of nitrendipine. We have studied the effect of nitrendipine on exchangeable body sodium (NaE) in this model. Eighteen male Sprague-Dawley rats had a left nephrectomy and after 14 days received subcutaneous injections of deoxycorticosterone (Percorten, CIBA) 12.5 mg three times weekly for 4 weeks and were given 22Na-labeled 1% saline plus 0.2% KCl to drink. They were fed a sodium-free diet. NaE, systolic blood pressure, and body weight were measured weekly. The animals were divided into two groups of nine, one group being given subcutaneous nitrendipine 5 mg/kg twice daily, while the control group was given vehicle only. Blood samples from conscious animals were drawn at the start and at the end of the study for measurement of plasma renin concentration (PRC) and haematocrit, and at the end for atrial natriuretic peptide (ANP) measurement. Twenty-four hour urine was collected at the end of the study from eight rats of each group, and urine and blood samples were taken for biochemical analysis. In the control rats, blood pressure rose from an initial mean of 140.6 +/- 1.7 (SEM) mm Hg to 187.2 +/- 6.5 (p less than 0.001) at week 4. In the nitrendipine-treated rats, blood pressure fell from 143.9 +/- 2 at week 0 to 127.2 +/- 3.3 mm Hg at week 4 (p less than 0.001). However, body weight rose similarly in both groups and there was no difference in NaE between the groups throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of polyethylene glycol by gavage on electrolyte and water excretion in the rat.

The effects of polyethylene glycol (PEG) 200 administered by gavage on electrolyte and water excretion were investigated in the rat. PEG 200 led, in intact rats, to dose-related increased drinking and to diuresis. In the first 2 h after PEG 200 administration, water consumption in intact rats exceeded urine output. PEG 200 enhanced the excretion of both sodium and potassium, but the sodium excretion was proportionately greater, resulting in an elevation of the urinary sodium/potassium ratio. Bilateral nephrectomy was not accompanied by increased drinking in PEG 200-treated rats, although raised serum osmolality was seen. Thus, given by gavage, PEG 200 is not an inert vehicle for drug administration.

Characteristics of antisera to antigenic forms of 1,25-dihydroxycholecalciferol.

Antisera to 1,25-dihydroxycholecalciferol were raised to 1,25-dihydroxycholecalciferol 25-hemisuccinate-bovine serum albumin, 1,25-dihydroxycholecalciferol 3-hemisuccinate-bovine serum albumin, 1,25-dihydroxycholecalciferol 3-hemisuccinate-porcine thyroglobulin and (5Z,7E)-(1S,3R)-1,3 dihydroxy-9,10-seco-24,25, 26,27-tetrakisnor-5,7,10(19)-cholestatrien-23-oic acid porcine thyroglobulin in rabbits. The antisera cross-reacted with a wide spectrum of vitamin D metabolites but their affinity was highest for 1,25-dihydroxycholecalciferol and some differentiated between ergo- and cholecalciferol metabolites. The presence of vitamin D binding protein and the pH of incubation markedly affected the sensitivity and specificity of antisera. A number of antisera were capable of measuring the normal plasma concentrations of vitamin D metabolites and their different affinities could be used for the measurement of 1,25-dihydroxyergocalciferol and 1,25-dihydroxycholecalciferol in plasma. None however were specific enough for the direct measurement of the metabolites in plasma. Immunisation increased the plasma concentration of endogenous 1,25-dihydroxyergo- and cholecalciferol in the animals.

Effect of chlorothiazide on serial measurements of exchangeable sodium and blood pressure in spontaneously hypertensive rats.

Chlorothiazide (100 mg/kg body weight) was given by gavage daily to spontaneously hypertensive rats for 4 weeks. Another group of spontaneously hypertensive rats was given only tap water and served as control. Measurements of total exchangeable sodium, blood pressure and weight were performed for 2 weeks before and for 4 weeks during treatment. Before treatment, exchangeable sodium, blood pressure and weight were similar in the two groups of rats. Chlorothiazide significantly attenuated the blood pressure increase in spontaneously hypertensive rats, the effect being most marked during the first 2 1/2 weeks of treatment and less thereafter. Rats in the chlorothiazide-treated group gained weight more slowly than did those of the control group. Exchangeable sodium, expressed as mmol/kg body weight, did not differ significantly between the two groups at any stage. When exchangeable sodium was expressed as mmol/rat, there was a more gradual rise in the chlorothiazide-treated animals, in accordance with their slower gain in weight. There was no temporal association between the antihypertensive effect of chlorothiazide and changes in exchangeable sodium. Thus whereas chlorothiazide treatment of spontaneously hypertensive rats slows the increase of both weight and exchangeable sodium, other mechanisms are apparently responsible for the antihypertensive action of the drug.

Early effects of ethinyloestradiol and norethisterone treatment in post-menopausal women on bone resorption and calcium regulating hormones.

The early effects of sex steroid therapy were assessed in 28 normal post-menopausal women, 18 treated with ethinyloestradiol and 10 with norethisterone. There was a reduction in the fasting urinary excretion of both calcium and hydroxyproline with both treatments, indicating reduced bone resorption. This was apparent after 1 week of therapy but became more marked after 3 weeks. These changes were not accompanied by any changes in plasma levels of calcitonin or parathyroid hormone. Patients receiving ethinyloestradiol showed a marked increase in plasma 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentration but this was explicable entirely in terms of increased plasma levels of vitamin D binding protein. There was no change in the free plasma level of 1,25(OH)2D. Patients treated with norethisterone showed no increase in plasma concentrations of 1,25(OH)2D. We conclude that both ethinyloestradiol and norethisterone have a rapid and similar effect in reducing bone resorption. This is not mediated via the plasma levels of the calcium regulating hormones.

Exchangeable sodium in DOC-salt and post-DOC-salt hypertension in rats.

Eighteen male Sprague-Dawley rats were fed a sodium-free diet and given NaCl (154 mmol/l) labelled with 22Na (37 Bq/l [1 microCi/l]) to drink. Following equilibration, each had a unilateral nephrectomy; 10 days later the animals started a series of 10 injections of deoxycorticosterone (12.5 mg twice-weekly for 5 weeks). Thereafter the animals were split into two groups, one to continue with DOC injections and diet as previously (DOC-salt), the other to stop DOC injections and continue a sodium-free diet and labelled saline of lower concentration (89 mmol/l) (post-DOC). During the period of DOC injections to both groups, blood pressure and exchangeable sodium rose significantly and were significantly correlated. In the post-DOC group, hypertension persisted and was not significantly different from that in the DOC-salt group. However, in the post-DOC-salt group, exchangeable sodium fell to levels similar to those found in uninephrectomized control animals of similar age which had never been given DOC or a high salt intake and had never been hypertensive. Thus an expanded sodium space does not contribute to maintenance of hypertension in the post-DOC-salt model.

Effect of hydralazine on serial measurements of exchangeable sodium and blood pressure in spontaneously hypertensive rats.

Hydralazine was dissolved in 0.5% drinking saline (40 mg/1000 ml) labelled with isotope 22Na and given to spontaneously hypertensive rats for four weeks. Another group of rats were given isotope labelled saline only and served as control. Measurements of total exchangeable sodium, blood pressure, pulse rate and weight were performed before and repeatedly during treatment. Before treatment exchangeable sodium, blood pressure, pulse rate, and weight were no different between the groups. The antihypertensive effect of hydralazine was marked and maintained throughout the experiment. No significant changes were found in pulse rate. Both groups gained weight similarly. Exchangeable sodium increased at the same rate in both groups along with the weight increase. Thus, chronic hydralazine treatment effectively reduces blood pressure in spontaneously hypertensive rats without causing measurable sodium or fluid retention.

Exchangeable sodium in Goldblatt one-kidney one-clip hypertension in the rat.

Exchangeable sodium (NaE), plasma active renin concentration and blood pressure were measured in rats with a sole remaining kidney before and after the development of hypertension induced by clipping of the single renal artery and again after unclipping. Control observations were made in sham-clipped and sham-unclipped uninephrectomized rats. Renal artery clipping caused hypertension and expansion of NaE, the latter being sustained throughout the 6 weeks during which the renal artery was constricted. Hypertension in the clipped rats was progressive over 6 weeks, whereas the expansion of NaE was not; thus the two measurements were not significantly correlated. Two rats which remained normotensive after clipping did not show expansion of NaE. Plasma active renin was elevated in comparison with the sham-clipped controls on the day after clipping, but not thereafter. Unclipping in hypertensive rats was followed by a return of NaE and blood pressure to control values. Both the sustained expansion of NaE and the transient rise in active renin probably contribute to the development of hypertension in this model, but neither alone nor together do they provide a full satisfactory explanation.

Exchangeable sodium measured serially in DOC-salt, post-DOC-salt, and Goldblatt hypertension in the rat.

A method for serial estimation of exchangeable sodium (NaE) levels in rats was developed and validated. The method can detect differences of 0.5 mmol per rat. The NaE level was found to have a constant relationship to the total body sodium content. Changes in the NaE level were found not to be a necessary accompaniment of two-kidney, one-clip hypertension. The NaE level was increased throughout 6 weeks of one-kidney, one-clip hypertension and reverted to control values with relief of hypertension after unclipping. The NaE level increased during the development of deoxycorticosterone (DOC)-salt hypertension but subsequently decreased during post-DOC-salt hypertension, although blood pressure remained elevated. Thus an increased NaE level was not necessary for the persistence of post-DOC hypertension.

Calcium malabsorption in the elderly: the effect of treatment with oral 25-hydroxyvitamin D3.

Calcium malabsorption is common in the elderly and may contribute to the development of age-related bone loss. To investigate its cause, we have measured radio-calcium absorption, plasma 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone in forty-eight elderly women with a normal plasma creatinine. Calcium malabsorption was associated with low 25-hydroxyvitamin D concentrations and was corrected by increasing these into the normal range by treatment with oral 25-hydroxyvitamin D3. Treatment also increased 1,25-dihydroxyvitamin D, and decreased parathyroid hormone concentrations. Before treatment, plasma parathyroid hormone was related to plasma creatinine but not to 25-hydroxyvitamin D, and the change in absorption on treatment correlated inversely with plasma creatinine. 51Cr EDTA clearance was measured in sixteen elderly women and confirmed that renal impairment was common even with a plasma creatinine in the normal range. Our results suggest that calcium malabsorption in the elderly is predominantly due to vitamin D deficiency; renal impairment is also common and contributes to the malabsorption by increasing the requirements for vitamin D.

The measurement of exchangeable sodium and total body sodium in rats in vivo compared with chemical analysis postmortem.

Measurements of body sodium content in rats were made in vivo by either neutron activation analysis or the use of the radioisotope, 22Na. The results were compared with estimates of TBNa of the carcases. Neutron activation analysis provided an accurate measure of total body sodium content. NaE, measured with 22Na, was consistently and quantitatively lower than total body sodium content. Each of these methods may be useful in the study of body sodium content in small animals during growth and during the evolution of experimental hypertension.

Exchangeable sodium in rats with Goldblatt two-kidney one-clip hypertension.

1. Exchangeable sodium (NaE) was measured serially in rats given a sodium-free diet to eat with sodium chloride solution (85 mmol/l) containing 22Na to drink. 2. After 15 days, nine rats had a left renal artery clip applied; nine had a sham operation. 3. There was no significant difference in NaE between the two groups during the 6 week period after clipping, at the end of which blood pressure was 189 +/- 8 mmHg (mean +/- SEM) in the clipped group and 150 +/- 2 mmHg in the sham-operated group (P less than 0.001). 4. When the clips were removed blood pressure in the hypertensive group fell to 144 +/- 4 mmHg. 5. On the first day after removal of the clip NaE was significantly lower in the clipped group than in the sham-operated group, but there were no significant differences thereafter. 6. Total body sodium (TBNa), measured at death, was consistently higher than NaE by a mean of 1.25 +/- 0.08 mmol, in hypertensive and control rats alike. 7. We conclude that changes in sodium balance are not a necessary accompaniment of of the development of hypertension in this two-kidney one-clip rat model.

Diurnal variations of plasma prolactin in growing sheep under two lighting régimes and the effect of pinealectomy.

The role of the pineal gland in mediating the stimulatory effect of long daylength on blood levels of prolactin was investigated in 24 growing castrated sheep. Eight were pinealectomized, eight were sham-pinealectomized and eight remained as unoperated control animals. After a preliminary period with 12 h light : 12 h darkness (12L : 12D) pairs of similar sheep were allocated to photoperiods of 16L : 8D or 8L : 16D for 15 weeks. Each animal was individually fed at the same level as its partner exposed to the other daylength. Blood samples were taken weekly by jugular venepuncture. On two occasions, once in the preliminary period (12L : 12D) and again 41 days after the start of the subsequent photoperiods, samples were taken through indwelling jugular catheters at frequent intervals for 24 h. The plasma samples were assayed for prolactin by radioimmunoassay and concentrations were higher in samples taken by jugular puncture. There was a consistent positive effect of daylength on plasma prolactin in sheep with pineal glands that did not occur in pinealectomized sheep. In contrast, pinealectomy did not block the marked rise in prolactin that occurred at dusk. It appears that the effect of the photoperiod on levels of plasma prolactin throughout the day and night is not mediated by the same mechanism as that which controls the surge of prolactin at dusk in the sheep.