Disabled-2 is expressed in adrenal zona glomerulosa and is involved in aldosterone secretion.

The differentiation of the adrenal cortex into functionally specific zones is probably due to differential temporal gene expression during fetal growth, development, and adulthood. In our search for adrenal zona glomerulosa-specific genes, we found that Disabled-2 (Dab2) is expressed in the zona glomerulosa of the rat adrenal gland using a combination of laser capture microdissection, mRNA amplification, cDNA microarray hybridization, and real-time RT-PCR. Dab2 is an alternative spliced mitogen-regulated phosphoprotein with features of an adaptor protein and functions in signal transduction, endocytosis, and tissue morphogenesis during embryonic development. We performed further studies to analyze adrenal Dab2 localization, regulation, and role in aldosterone secretion. We found that Dab2 is expressed in the zona glomerulosa and zona intermedia of the rat adrenal cortex. Low-salt diet treatment increased Dab2-long isoform expression at the mRNA and protein level in the rat adrenal gland, whereas high-salt diet treatment did not cause any significant modification. Angiotensin II infusion caused a transient increase in both Dab2 isoform mRNAs in the rat adrenal gland. Dab2 overexpression in H295R human adrenocortical cells caused an increase in aldosterone synthase expression and up-regulated aldosterone secretion under angiotensin II-stimulated conditions. In conclusion, Dab2 is an adrenal gland zona glomerulosa- and intermedia-expressed gene that is regulated by aldosterone secretagogues such as low-salt diet or angiotensin II and is involved in aldosterone synthase expression and aldosterone secretion. Dab2 may therefore be a modulator of aldosterone secretion and be involved in mineralocorticoid secretion abnormalities.

Effects of dietary modification in dogs with early chronic valvular disease.

BACKGROUND: The potential benefits of nutritional modification in early canine cardiac disease are not known. HYPOTHESIS: We hypothesized that echocardiographic, neuroendocrine, and nutritional variables will differ between dogs with asymptomatic chronic valvular disease (CVD) and healthy controls, and that a moderately reduced sodium diet enriched with antioxidants, n-3 fatty acids, taurine, carnitine, and arginine will alter these variables in dogs with CVD. METHODS: Echocardiography was performed and blood was collected. After baseline comparison with healthy controls, all dogs with CVD were fed a low-sodium run-in diet for 4 weeks, reevaluated, and then randomized to receive either the cardiac diet or a placebo diet for 4 weeks. RESULTS: At baseline, dogs with CVD (n = 29) had significantly lower circulating sodium, chloride, arginine, and methionine concentrations and higher plasma concentrations of atrial natriuretic peptide compared to healthy controls. In dogs with CVD, plasma aldosterone concentration and heart rate increased significantly after 4 weeks of eating the run-in diet. The cardiac diet group (n = 14) had larger increases in levels of cholesterol (P = .001), triglycerides (P = .02), eicosapentaenoic acid (P < .001), docosahexaenoic acid (P < .001), total omega-3 fatty acids (P < .001), vitamin C (P = 0.04), alpha-tocopherol (P < .001), and gamma-tocopherol (P < .001) compared to the placebo diet group (n = 15). The cardiac diet group also had larger reductions in maximal left-atrial dimension (P = .003), left-ventricular internal dimension in diastole (P = .03), and weight-based maximal left-atrial dimension (P = .03). CONCLUSIONS AND CLINICAL IMPORTANCE: Observed changes in both blood variables and echocardiographic measurements warrant additional studies on dietary modifications in dogs with early CVD.

Ebstein's anomaly in a beagle dog.

An intact male beagle dog aged 1 year was referred because of shortness of breath, exercise intolerance and cardiac murmur. Based on the results from electrocardiography, thoracic radiography and echocardiography, the dog was diagnosed as Ebstein's anomaly. Although the orally administered digoxin, vasodilators and diuretics partially improved congestive signs, the dog became to be refractory and died 20 months after the diagnosis. Necropsy confirmed malformation and apical displacement of the basal attachment of tricuspid valve leaflets.

Additive effects of a sodium chloride restricted diet and furosemide administration in healthy dogs.

OBJECTIVE: To determine the effects of a low or high sodium (Na) diet with or without furosemide administration on plasma electrolyte concentrations and the renin-angiotensin-aldosterone system in healthy dogs. ANIMALS: 20 healthy adult dogs. PROCEDURE: Dogs were randomly allotted to 4 groups of 5 dogs each as follows: dogs fed a low Na diet (0.08% Na and 0.8% chloride [CI] on a dry matter [DM] basis); dogs fed a low Na diet with added NaCl (1.0% Na and 2.2% Cl on a DM basis); dogs fed a low Na diet and treated with furosemide (2 mg/kg of body weight, PO, q 12 h); and dogs fed a low Na diet with added NaCl and treated with furosemide. Plasma electrolyte concentrations were measured on days 0, 21, and 35. Plasma renin activity and aldosterone concentration were analyzed by use of radioimmunoassays on days 0, 21, 35, and 53. RESULTS: Furosemide treatment significantly decreased plasma Cl concentration and significantly increased plasma renin activity and aldosterone concentration. Dogs fed a low Na diet had significantly higher plasma renin activities and plasma aldosterone concentrations. A significant interaction between a low Na diet and furosemide administration resulted in the lowest plasma Cl concentrations, highest plasma renin activities, and highest plasma aldosterone concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy dogs, feeding a low Na diet and administering furosemide resulted in an additive effect on plasma Cl concentration, renin activity, and aldosterone concentration, which may be an important consideration for treating dogs with cardiac disease.

Effect of short-term treatment with bumetanide, quinapril and low-sodium diet on dogs with moderate congestive heart failure.

OBJECTIVE: To evaluate the effect of bumetanide, quinapril and a low-sodium diet on clinical response tolerance and side-effects on dogs with moderate congestive heart failure. DESIGN: A prospective clinical study, using 32 client-owned dogs with naturally occurring disease. PROCEDURE: Thirty-two dogs diagnosed with congestive heart failure (International Small Animal Cardiac Health Council stage II) due to mitral valve disease were included. During 4 weeks, patients received 0.5 mg/kg quinapril (Ectren, Menarini), 0.1 mg/kg bumetanide (Fordiuran, Boehringer Ingelheim) and a low sodium diet (CNM-CV, Purina) was fed. All dogs were examined weekly and results were treated statistically. RESULTS: The treatment was safe, effective and well-tolerated and no major side-effects were observed. There were no significant changes in measured haematological and biochemical variables, including serum electrolyte concentrations and urinary fractional excretion of electrolytes. CONCLUSION: This study suggests that the combined treatment with bumetanide, quinapril and low-sodium diet for controlling moderate CHF due to mitral insufficiency in dogs is simple, easy-to-administer and effective in controlling clinical signs and prompting improvement even after short-term treatment.

Clinical, echocardiographic, and neurohormonal effects of a sodium-restricted diet in dogs with heart failure.

The use of low-sodium diets in dogs with heart failure is common practice, but randomized, double-blind studies have not been conducted to examine the benefits or problems with this approach. The purpose of this study was to determine the effects of a low-sodium diet on clinical, echocardiographic, and neurohormonal parameters in dogs with heart failure. Dogs with stable chronic heart failure were fed exclusively a low-sodium (LS) and a moderate-sodium (MS) diet for 4 weeks each in a randomized, double-blind, crossover design. At days 0, 28, and 56, echocardiography and thoracic radiography were performed, and blood was analyzed for electrolytes and neurohormones. Fourteen dogs completed the study (9 with chronic valvular disease and 5 with dilated cardiomyopathy). Electrolyte abnormalities were common during the study, and serum sodium and chloride concentrations decreased significantly on the LS diet. Neurohormones did not change significantly between diet groups. Maximum left atrial (P = .05) and standard left atrial (P = .09) size decreased on the LS diet. For dogs with chronic valvular disease, vertebral heart score (P = .05), left ventricular internal dimension in diastole (P = .006) and systole (P = .02), standard left atrial dimension (P = .03), maximum left atrial dimension (P = .02), end-diastolic volume index (P = .02), and end-systolic volume index (P = .04) decreased significantly on the LS diet compared to the MS diet. Although analysis of these data suggests some benefits of a low-sodium diet, future studies with improved study design are needed to further evaluate the advantages and disadvantages of sodium restriction in dogs with heart failure.

Dietary management of feline chronic renal failure: where are we now? In what direction are we headed?

Dietary modification is of primary importance in managing cats with chronic renal failure. Diets designed for cats with chronic renal failure are typically formulated to be pH neutral and contain reduced quantities of protein, phosphorus and sodium and an increased quantity of potassium. These changes in diet formulation are designed to ameliorate clinical signs of renal failure by adapting dietary intakes to meet the limited ability of failing kidneys to adapt to the normal range of dietary intakes. Important recent clinical trials support the therapeutic value of dietary therapy in cats with chronic renal failure.

Sodium economy in white-tailed deer (Odocoileus virginianus).

Sodium is considered the mineral most limiting to growth and reproduction of mammalian herbivores worldwide. Notwithstanding the large database on physiological adaptations to low sodium intake, information on maintenance sodium requirements and sodium dynamics of mammals is depauperate. We measured sodium intake and output in adult, nonreproductive white-tailed deer (n = 15) over four seasons to estimate daily requirements for sodium on a seasonal and an annual basis. Dietary sodium content was based on best available predictions of sodium requirements. With regression techniques, we estimated metabolic fecal excretion and endogenous urinary losses of sodium. Average daily sodium requirement, defined as the minimum sodium intake at which intake equaled excretion, was estimated to be 3.27 mg kg-1 body mass d-1. Seasonal estimates did not vary. We propose that sodium requirements for maintenance in mammalian herbivores scale to body mass at an exponent that is similar to that for metabolic rate and forage intake (0.71-0.75). Development of an allometric relationship between sodium need and body mass would permit stronger inference regarding the role of sodium in population regulation, foraging decisions, or distribution and movements of mammalian herbivores.

Effects of certain vasoactive agents on the long-term pattern of blood pressure, heart rate, and motor activity in cats.

OBJECTIVE: To determine whether a diurnal pattern exists in cardiovascular variables and motor activity, and whether pharmacologic agents that decrease (angiotensin converting enzyme inhibitor) or increase (N omega-nitro-L-arginine methyl ester [L-NAME]) blood pressure alter the pattern. ANIMALS: 6 clinically normal cats. PROCEDURE: Radiotelemetric implants were used to measure systemic arterial pressure, heart rate, and motor activity in conscious cats maintained in cages. Measurements were obtained during absence of treatment (control), treatment with dietary salt restriction plus an inhibitor of angiotensin converting enzyme (2.5 mg of lisinopril, PO, daily) and treatment with an inhibitor of nitric oxide production (0.1% L-NAME in the drinking water). RESULTS: A diurnal pattern in arterial pressure and motor activity was observed, with highest values obtained during presence of laboratory personnel. Mean values of arterial pressure obtained during light hours varied from those obtained during darkness (P < 0.05), but by < 3 mm of Hg. Dietary sodium restriction did not have an appreciable effect on arterial pressure, but the combined administration of a low sodium diet plus lisinopril decreased (P < 0.05) measured indices of arterial pressure. Administration of L-NAME increased arterial pressure (P < 0.05) and altered its diurnal pattern. CONCLUSIONS: Although a diurnal pattern of arterial pressure was observed, variations were mostly associated with presence of human beings. Administration of L-NAME, but not lisinopril, altered this diurnal pattern. CLINICAL RELEVANCE: Factors that modify arterial pressure may alter the diurnal pattern of cardiovascular variables. In measuring arterial pressure in cats, the effects of human contact may artifactually increase such variables.

Cambios histoquímicos en la mucosa gástrica de ratas por el consumo de dietas hipersódicas durante el desarrollo / Histochemical changes in rats' gastric mucosa induced by the intake of high salt diets during postnatal development

La barrera de la mucosa gástrica es el principal mecanismo de protección para el estómago; sin embargo, existen elementos dietéticos irritantes consumidos a diario que pueden llegar a dañar dicha barrera, tal es el caso del cloruro de sodio o sal común. El presente estudio muestra que el consumo crónico de dietas hipersódicas durante el desarrollo posnatal de la rata Wistar, altera el tipo y distribución de mucopolisacáridos de la mucosa gástrica, presentando mucinas predominantemente de tipo intestinal (ácida), este cambio se puede considerar como una variable importante para el diagnóstico de diversas alteraciones gástricas

The use of diets containing high levels of zinc for controlling early growth in female broiler chicks.

A study was carried out with White Rock female chicks to evaluate the possibility of using dietary Zn supplied as ZnO, to control feed intake and weight gain during the period of 1 to 3 wk of age. The levels of supplemental Zn tested were 0, 0.25, 0.50, and 1.0% (Experiment 1); 0, 0.65, 0.75, and 0.85% (Experiment 2); 0.7 and 0.8% (Experiment 3). The effect of Zn supplementation was compared with that of a low sodium chloride diet (L-NaCl-D) and of severe feed restriction (SFR), which was calculated to supply energy only for maintenance (Experiments 1 and 3, respectively). The compensatory growth of the chicks from 3 to 4 wk of age was also evaluated. Feed intake and weight gain were negatively proportional to the levels of dietary Zn supplementation and there were significant (P < 0.02 and P < 0.01, in Experiments 1 and 2, respectively) negative correlations between supplemental dietary Zn levels and relative weight gains (values observed in the unsupplemented diet = 100%). The effects of L-NaCl-D and SFR on decreasing weight gain were calculated, according to the equations obtained in Experiments 1 and 2 to be equivalent to these of 0.58 to 0.65% and 0.78 to 0.87% Zn supplementation, respectively. Relative weight gain and feed efficiency of the chicks from 3 to 4 wk of age, after withdrawal of the growth-depressing factors, were positively related to the degree of growth depression during 1 to 3 wk of age; however, the intensity of recovery from a similar degree of growth depression induced by L-NaCl-D, SFR, or dietary Zn was least in the last mentioned treatment. It is concluded that dietary Zn supplementation can be used as an efficient tool for controlling early growth of young broiler breeder chicks.

Effects of mild mitral valve insufficiency, sodium intake, and place of blood sampling on the renin-angiotensin system in dogs.

In 23 Cavalier King Charles Spaniels, 12 with mild mitral valve insufficiency (MVI) and 11 controls, the activity of the renin-angiotensin system (RAS) was assessed by measuring the plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in 5 different settings. The dogs were sampled at the clinic before the trial and thereafter at home and at the clinic; during both a period on control diet and a period on low sodium diet. The dogs with mild MVI had the highest median PRA and PAC in all 5 settings. An analysis of variance accordingly showed that dogs with mild MVI had significantly higher PRA (p < 0.0001) and PAC (p = 0.03) than controls, and that the sodium intake and place of blood sampling did not significantly affect this finding. The sodium intake had highly significant effects on PRA and PAC, and the place of blood sampling had no significant effects on PRA and PAC. The activity of angiotensin-converting enzyme in serum was lower in dogs with mild MVI than in controls (p = 0.0002). The plasma levels of endothelin-1, atrial natriuretic peptide, and arginine vasopressin, 3 peptides of pathophysiologic importance in congestive heart failure, were not significantly changed by the disease. The early activation of the RAS in dogs with MVI suggests that the valvular disease process itself might be the cause of the activation, but confirmation of this requires further studies.

Effects of a low sodium diet with a high potassium content on plasma endothelin-1, atrial natriuretic peptide and arginine vasopressin in normal dogs.

Eight clinically healthy male beagle dogs received a low sodium diet for 5 weeks. Before and after this period the dogs received a control diet for 3 weeks. Both diets provided the dogs with approximately 6.8 mmol K+/kg/day. Neither introducing nor withdrawing the low sodium diet changed the plasma concentrations of endothelin-1 (ET-1), atrial natriuretic peptide (ANP) and arginine vasopressin (AVP). Pooled data from the control periods were not different from the low sodium period for either ET-1 (2.31 pg/ml and 2.09 pg/ml, P = 0.21), ANP (42.51 pg/ml and 38.99 pg/ml, P = 0.44) or AVP (4.14 pg/ml and 4.16 pg/ml, P = 0.91). It was concluded that ET-1, ANP and AVP in normal dogs are unaffected by a 6-fold change in sodium intake in the presence of a high potassium intake.

Some effects of a low sodium diet high in potassium on the renin-angiotensin system and plasma electrolyte concentrations in normal dogs.

Eight normal male Beagle dogs received 0.7 mmol Na+/kg/day for 5 weeks and 4.0 mmol Na+/kg/day in one 3 week control period preceding and another similar period following the low sodium period. The dogs received 6.8 mmol K+/kg/day throughout the study. The median plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were higher in the low sodium period than in the following control period (0.67 versus 0.28 ng/ml/h, p < 0.0001) and (204 versus 31 pg/ml, p < 0.0001). PRA and PAC quickly stabilized on a new steady level in response to altered intake of sodium chloride. The angiotensin-converting enzyme (ACE) activity was not changed by the altered intake of sodium chloride. The plasma concentrations of sodium and chloride were increased during the low sodium period. This could be due to an indirect effect of the high potassium intake of the dogs. Potassium leads to an increased secretion of aldosterone and thereby to an increased retention of sodium and chloride in the kidney. The possible implications of a high potassium content in a low sodium diet are discussed.

Efficacy of digoxin for treatment of cats with dilated cardiomyopathy.

The role of digoxin in treatment of cats with dilated cardiomyopathy and other forms of myocardial failure is unclear. We evaluated the chronotropic and inotropic effects of digoxin by comparing baseline, noninvasive indices of cardiac performance with those obtained after 9 +/- 1.3 (mean +/- SEM) days of digoxin treatment in 6 cats with heart failure attributable to dilated cardiomyopathy. Two-dimensionally directed, M-mode echocardiography and electrocardiography were used to determine left ventricular shortening fraction, preejection period (PEP), ejection time (LVET), PEP to LVET ratio, velocity of circumferential fiber shortening, electromechanical systole, heart rate, and PR interval. Treatment consisted of administration of furosemide (mean dosage, 2.4 mg/kg of body weight/day), digoxin in tablet form (approximately 0.01 mg/kg, q 48 h), aspirin (80 mg, q 48 h), and a commercial low-salt diet. In addition, 2 cats were administered short-term, low-dose fluids IV, and 2 were given taurine supplementation at rates of 500 and 1,000 mg/day. Other off-loading or inotropic agents were not administered. Therapeutic or toxic serum digoxin concentration was achieved in all cats. Significant (P less than 0.05) improvement was detected in mean values for shortening fraction, PEP, PEP to LVET ratio, and velocity of circumferential fiber shortening. Mean electromechanical systole and LVET did not change significantly. Improvement, as assessed by indices of cardiac function, was documented in 4 of the 6 cats treated with digoxin, including the 2 cats given taurine supplementation. In the cats given taurine, positive inotropic effect was observed prior to the time when taurine-induced improvement in ventricular function is detectable.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathophysiologic response of the juxtaglomerular apparatus to dietary sodium restriction in the dog.

Pathophysiologic changes in the juxtaglomerular apparatus (JGA) of the dog were induced by 10 days of dietary sodium restriction (less than 1 mEq of Na+/day). Plasma renin activity increased 12-fold and plasma aldosterone values increased 60-fold, whereas urinary sodium excretion decreased precipitously. Urinary potassium excretion remained within normal values throughout the period of sodium restriction. The JGA cell counts, determined by light microscopy, were significantly (P = less than 0.05) increased after 2 days of sodium restriction and remained increased through day 10. Adrenal gland weights and the cross-sectional width of the zona glomerulosa were not altered. Ultrastructurally, JGA cells showed progressive hypertrophy and hyperplasia. The Golgi apparatus became more prominent. The endoplasmic reticulum increased, as did the number of ribosomes. Cytoplasmic secretory granules increased in number and size from day 2 through day 6. On days 8 and 10, fewer and smaller secretory granules were encountered, even though plasma renin and aldosterone values continued to increase. In the dog maintained in a balanced sodium state, little renin is stored in cytoplasmic granules of the juxtaglomerular cells. Short-term stimulation results in increased plasma renin values and increased production and storage of renin in JGA cells. Continued stimulation results in depletion of cytoplasmic stores, although plasma renin content continues to rise, suggesting that renin is produced and secreted directly during more prolonged stimulation.