A preclinical pharmacokinetic and pharmacodynamic approach to determine a dose of spironolactone for treatment of congestive heart failure in dog

Guyonnet, J., Elliott, J., Kaltsatos, V. A preclinical pharmacokinetic and pharmacodynamic approach to determine a dose of spironolactone for treatment of congestive heart failure in dog. J. vet. Pharmacol. Therap. 33 , 260–267. Fifteen Beagle dogs were used to describe the anti‐aldosterone effect of spironolactone (0, 0.8, 2 and 8 mg/kg) in a hyperaldosteronism model. The magnitude of the aldosterone response observed in this model was very similar to the one described in a dog with congestive heart failure (CHF). Each dog was allocated to a treatment group according to a 5 × 5 Latin square crossover design for five periods with a washout period of 7 days between each period. A maximal possible effect (E_max) model was employed to determine the basic pharmacodynamic parameters of spironolactone, measured by high‐performance liquid chromatography, in antagonizing the renal effects of aldosterone. The change in urinary sodium/potassium ratio in response to a single dose of aldosterone was calculated. The inhibition of this response by oral spironolactone administration was assessed. Aldosterone alone decreased sodium excretion by approximately 35% and urinary potassium concentrations increased by 25%, whereas the urine volume decreased, as expected. The effect of aldosterone on the Na⁺/K⁺ ratio was completely reversed (88% inhibition) at a dose of 2 mg spironolactone/kg, while at the dose of 0.8 mg/kg, partial reversal was seen (27.5% inhibition). Urine flow rate was not significantly modified by either aldosterone treatment or aldosterone with spironolactone. The dose of spironolactone required to inhibit the action of aldosterone by 50% (ED₅₀) was estimated to be 1.08 ± 0.28 mg/kg. The E_max was a ratio of 1.089 ± 0.085, close to the observed value in negative control group (1.00 ± 0.18). The proposed spironolactone dose using this E_max model was 2 mg/kg b.w. once daily for the management.     

Genetic-diet interactions in the Hyperkalemic Periodic Paralysis syndrome in Quarter Horses fed varying amounts of potassium: I. Potassium and sodium balance, packed cell volume and plasma potassium and sodium concentrations

Six broodmares that were genetically tested to be heterozygous (H/N) and six broodmares that were tested to be homozygous negative (N/N) for Equine Hyperkalemic Periodic Paralysis (HYPP), that were descendents of the same stallion, were used in a replicated 3×3 Latin square experiment to determine the genetic-diet relationships in the HYPP syndrome.¹ The mares were fed rations consisting of 65% pelleted concentrate and 35% Coastal Bermuda grass hay that provided 1.1 (diet A), 1.9 (diet B) and 2.9% (diet C) potassium. The experimental periods were 14 days long, resulting in 28 meals per period. At meals 1 and 27, blood samples were taken every 30 minutes for 12 hours and every 10 minutes from 2 to 5 hours post-feeding. Total urine and fecal collections were made on the last 4 days of each period.Water, feed and fecal samples were analyzed for sodium and potassium content. Blood was analyzed for packed cell volume (PCV) and plasma potassium (K⁺) and sodium (Na⁺) concentrations.Apparent absorption of potassium was 99.8% across all diets, and potassium was excreted principally in the urine. More potassium was retained when the horses were fed diet B than diets A or C. Apparent absorption of sodium was 99.6% with no difference by diet. Neither potassium nor sodium balances were affected by HYPP status.There was no post-prandial pattern of plasma K⁺ concentration seen when the horses were fed the low potassium diet. When fed the higher potassium diets, they had greater plasma K⁺ values and exhibited a post-prandial peak at 2 to 5 hours after feeding. This peak occurred in all of the horses, meaning that plasma K⁺ cannot be used as a diagnostic aid for the presence of the HYPP mutation. By meal 27, some adaptation had occurred resulting in lower plasma K⁺ values when the horses were fed the higher potassium diets. The horses had increased plasma K⁺ concentrations throughout the post-prandial period while fed diet B compared to diet A, agreeing with the positive potassium balance seen in this experiment. The HYPP H/N horses had lower plasma Na⁺ concentrations in the early post-prandial hours and continuously greater PCV values than the HYPP N/N horses.     

Potassium concentration in equine red blood cells: Normal values and correlation with potassium levels in plasma

The concentration of potassium in plasma and in red blood cells was determined in 948 horses. The coefficient of correlation between the two parameters was low. In 436 of these horses, which were clinically healthy, the red blood cell potassium (RBCK⁺) levels did not fit within a normal distribution curve, but a bimodal distribution was observed with a section point at 90 mmol/litre. In 90 per cent of these normal horses, mean RBCK⁺ content was 97.5 mmol/litre. In the remaining 10 per cent, mean RBCK⁺ concentration was 93.8 mmol/litre. A subdivision into a ‘low potassium group’ and a ‘high potassium group’ was made. In 10 out of 15 horses in the ‘low potassium group’, bimonthly sampling over a period of one year showed that RBCK⁺ content remained low. In the remaining five horses an increase was observed.     

Plasma renin activities, angiotensin II concentrations, atrial natriuretic peptide concentrations and cardiopulmonary function values in dogs with severe heartworm disease

Relationships among plasma renin activities (PRA), plasma angiotensin II (ATII) concentrations, atrial natriuretic peptide (ANP) concentrations and cardiopulmonary function values were examined in dogs with ascitic pulmonary heartworm disease and acute- and chronic-vena caval syndrome (CS). PRA, plasma ATII concentration and plasma ANP concentration tended to be higher or were significantly higher in dogs with ascites, acute- and chronic-CS. PRA correlated significantly with plasma ATII concentration, WBC count, ALP activity, plasma concentrations of urea nitrogen, creatinine, sodium, potassium, and chloride, right ventricular endodiastolic pressure and right atrial pressure. Plasma ATII concentration correlated significantly with WBC count, plasma concentrations of urea nitrogen, sodium, and potassium, right ventricular endodiastolic pressure and right atrial pressure. Plasma ANP concentration did not correlate with PRA or ATII concentration, but correlated significantly only with pulmonary arterial pressure.     

Association of hyponatremia and hyperglycemia with outcome in dogs with congestive heart failure

Objective: To evaluate plasma sodium and glucose concentrations in dogs with congestive heart failure (CHF) prior to treatment and evaluate the differences between survivors and non‐survivors. Design: Retrospective study. Animals: Fifty‐nine dogs with CHF prior to receiving cardiac medication. Interventions: None. Measurements and main results: The mean plasma sodium concentration in dogs with CHF was below the reference range (144–156 mmol/L) and significantly lower (P=0.009) in non‐survivors (141±6 mmol/L) compared with survivors (147±4 mmol/L). The mean plasma glucose concentration was above the reference range (76–117 mg/dL) and significantly higher (P=0.004) in non‐survivors (128±52 mg/dL) compared with survivors (100±13 mg/dL). Forty‐four percent of non‐survivors had concurrent low plasma sodium and high plasma glucose concentrations, whereas no survivors had both abnormalities (P<0.0001). Conclusions: Lower plasma sodium and higher plasma glucose are associated with a worse outcome in dogs with CHF.     

Failure of loop diuretics to induce nursing sickness in mink at weaning.

Nursing sickness in mink is thought to be precipitated by inadequate salt intake, whether this is due to inadequate salt levels in the diet or inadequate total dietary intake. To test this hypothesis, lactating females raising large litters were given 2 daily intramuscular injections of the loop diuretic furosemide (Lasix, 4 + 4 mg/kg/day) for 2.5 d during the normal weaning period 6 wk after parturition or served as untreated controls. Following the same protocol, barren mink (i.e. unsuccessfully mated females) were treated similarly. Dams were carefully inspected for clinical signs of nursing sickness during and after the treatment. Urinary osmolality and concentrations of sodium, potassium, chloride, creatinine and carbamide (urea) were measured prior to treatment (day 1) and on day 3, immediately before and 4 h after the final diuretic treatment. Plasma concentrations of aldosterone and cortisol were determined by radioimmunassay 4 h after the last injection with furosemide on day 3. Biochemical changes in urine (a low osmolality, low concentrations of carbamide and creatinine, and extremely low sodium concentrations) and in plasma (aldosteronism) similar to those found in nursing sickness were elicited in the nursing dams. Nevertheless, none of the dams developed overt clinical signs of nursing sickness. It is concluded that the biochemical signs of volume and salt depletion associated with nursing sickness are sequelae rather than etiological factors of this disorder.     

Activation of the Renin-Angiotensin System in Dogs With Asymptomatic and Mildly Symptomatic Mitral Valvular Insufficiency

The renin-angiotensin system has important pathophysiologic implications in the development of congestive heart failure. The activity of the renin-angiotensin system early in the course of heart disease and heart failure in dogs was evaluated by measuring the plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in 18 Cavalier King Charles Spaniels with asymptomatic or mildly symptomatic mitral valvular insufficiency, and in 18 healthy Cavalier King Charles Spaniels. All dogs were unmedicated and had no other diseases. The PRA was high in the dogs with mitral valvular insufficiency (median 3.44 ng/mL/h, interquartile interval 2.59 to 8.66 ng/mL/h) compared with the controls (median 2.51 ng/mL/h, interquartile interval 1.44 to 3.58 ng/mL/h). The PAC was also higher in the dogs with mitral insufficiency (median 53 pg/mL, interquartile interval 33 to 138 pg/mL) than in the control group (median 27 pg/mL, interquartile interval 11.5 to 54 pg/mL). However, there was considerable overlap between the 2 groups in both PRA and PAC. It was concluded from these data that there is early activation of the renin-angiotensin system in some Cavalier King Charles Spaniels with mitral valvular insufficiency. Further prospective studies are needed to determine if early intervention with angiotensin-converting enzyme inhibitors will be valuable in this group of patients.     

Changes in renin‐angiotensin‐aldosterone system during cardiac remodeling after mitral valvuloplasty in dogs

BackgroundInformation regarding changes in renin‐angiotensin‐aldosterone system (RAAS) during cardiac remodeling after mitral valvuloplasty (MVP) in dogs remains lacking.Hypothesis/ObjectivesTo assess the longitudinal effects of MVP on circulating RAAS activity.AnimalsEight client‐owned dogs receiving MVP for myxomatous mitral valve disease (MMVD).MethodsThis is a cohort study. Plasma renin activity (PRA), angiotensin II (AT2), aldosterone (PAC), blood urea nitrogen (BUN), and creatinine concentrations, were measured in these dogs before (baseline) and at 3 consecutive monthly follow‐ups (Post‐1M, Post‐2M, Post‐3M). Echocardiography was concomitantly used to assess the process of cardiac recovery after MVP.ResultsThe echocardiography revealed a significant decrease in LVIDDN, LA/Ao, FS, E velocity, E/A, E′ sep, S′ lat, E′ lat, and A′ lat after MVP compared with baseline (P < .05). There was a significant reduction in the PRA (2.45, 3.05, 2.74 vs 8.8 ng/mL/h; P = .002), AT2 (466, 315, 235 vs 1200 pg/mL; P = .009), and PAC (39.88, 47, 54.62 vs 179.5 pg/mL; P = .01), respectively at Post‐1M, Post‐2M, Post‐3M compared to the baseline. Additionally, BUN and creatinine concentrations decreased from Post‐1M. The RAAS variables showed significant, weak to moderate, relationship with selected echocardiographic variables.Conclusions and Clinical ImportanceMitral valvuloplasty contributes to decreased RAAS activity in MMVD dogs, which paralleled the process of cardiac reverse remodeling up to Post‐3M. This information facilitates formulating strategies to optimize clinical outcomes for dogs after MVP.     

Effects of three infusion fluids with different sodium chloride contents on steady‐state serum concentrations of bromide in dogs

Potassium bromide overdose (bromism) in the management of canine epilepsy has been known. However, a protocol to reduce bromide concentrations rapidly has not been previously established. The effects of three infusion fluids with different chloride contents on the steady‐state serum concentrations of bromide in beagles were determined. After stabilization of the serum bromide concentrations, seven dogs were infused with saline (Na⁺ 154 mmol/L; Cl^? 154 mmol/L), lactated Ringer's (Na⁺ 131 mmol/L; Cl^? 110 mmol/L), or maintenance solutions (Na⁺ 35 mmol/L; Cl^? 35 mmol/L) at a rate of 2 or 10 ml kg^?1 hr^?1 for 5 hr. Serum and urine were collected hourly, and the bromide concentrations were measured. When saline and lactated Ringer's solutions were infused at a rate of 10 ml kg^?1 hr^?1 for 5 hr, serum bromide concentrations were decreased by 14.24% and urine bromide concentrations by 17.63%, respectively. Of all compositions of infusion fluids, only sodium and chloride contents were associated with the decreased serum concentrations and the increased renal clearance of bromide. In summary, saline and lactated Ringer's solutions reduced serum bromide concentrations in a sodium chloride‐dependent manner in dogs were found when infused at 10 ml kg^?1 hr^?1 for 5 hr.     

Investigation of the role of aldosterone in hypertension associated with spontaneous pituitary-dependent hyperadrenocorticism in dogs

The aim of this study was to evaluate the role of aldosterone as an initiating and/or perpetuating factor in hypertension associated with pituitary-dependent hyperadrenocorticism (PDH) in dogs. Thirteen dogs with PDH and 11 healthy control dogs were used. In all dogs, arterial blood pressure and plasma sodium, potassium, basal aldosterone, post-ACTH aldosterone, basal cortisol and post-ACTH cortisol concentrations were measured. The tests were repeated 10 days and three months after the beginning of o,p'-DDD treatment in PDH dogs. In untreated PDH dogs, plasma aldosterone was significantly decreased, whereas cortisol, sodium and arterial blood pressure were significantly increased compared to healthy dogs. Hypertension remained in most treated PDH dogs despite normalisation of cortisol and persistently low aldosterone levels. These results did not demonstrate that aldosterone is involved in the development and perpetuation of hypertension in PDH. However, glucocorticoids seemed to play a major role as an initiating and perpetuating factor in PDH in dogs.     

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.     

External balance of water and electrolytes in the horse

The components of the daily external water and electrolyte balances of five normal Standardbred geldings with a mean body weight of 427 kg, were determined over 14 day periods. The mean value of daily total water intake (a summation of free, combined and metabolic water intake) for the group was 27.6 litres, that is, 64.4 ml/kg body weight, while mean values for ambient temperature and humidity ranged from 16 to 25 degrees C and 55.4 to 75.5 per cent, respectively. The mean daily urine volume of 9.9 litres (23.2 ml/kg) for the group, was found to exceed the mean faecal water output of 7.2 litres (16.9 ml/kg). The mean output of sodium for the five animals, in urine and faeces, was 780 mmol or 79 per cent of the intake. The mean output of potassium, chloride, calcium and magnesium were 3163, 2521, 1824 and 1448 mmol or 95, 84, 74 and 75 per cent, respectively of intake. The sodium and potassium not accounted for in urine and faeces may well have been lost in sweat. Results are discussed and compared with those of a previous external balance study in the horse.     

A Retrospective Study of Aldosterone Secretion in Normal and Adrenopathic Dogs

A retrospective study on stored plasma from normal dogs and dogs with pituitary dependent hyperadrenocorticism (PDH), pituitary dependent hyperadrenocorticism controlled by mitotane (o,p'-DDD),* iatrogenic hyperadrenocorticism, and hypoadrenocorticism was conducted to determine if alterations in aldosterone production exist in these disorders. The plasma aldosterone concentration (PAC) was measured by radioimmunoassay immediately before and 1 hour after adrenocorticotropic hormone (ACTH) administration (0.5 IU/kg, intravenously [IV]). PACs increased significantly when ACTH was administered to normal dogs. Dogs with PDH had a lower baseline PAC, but their PAC increased to levels similar to that of normal dogs after ACTH administration. In dogs with PDH controlled by o,p'-DDD therapy, the response to ACTH was significantly less than that of normal dogs or dogs with untreated PDH. Dogs with iatrogenic hyperadrenocorticism had a lower baseline and post-ACTH PAC than normal dogs. Dogs with hypoadrenocorticism had a normal basal PAC, but showed no significant increase in PAC following ACTH administration. These findings suggest that PACs are significantly altered in a variety of adrenal diseases, and that the ACTH stimulation test may be useful when evaluating aldosterone secretion in adrenopathic disorders. In addition, at therapeutic dosages, o,p'-DDD treatment was associated with a decrease in basal and post-ACTH PACs in dogs with PDH.     

Some physiological and biochemical effects of intravenous fluid administration during halothane anaesthesia in the dog

Six dogs with previously implanted arterial, central venous, pulmonary arterial and left atrial catheters received halothane anaesthesia, and halothane anaesthesia plus administration of a balanced electrolyte solution given over one hour, in a cross-over experiment. Parameters measured included temperature, heart rate (HR), respiratory rate (f), arterial and mixed venous blood-gases and acid-base parameters, mean arterial pressure ( AP ), mean pulmonary artery pressure ( PAP ), mean left atrial pressure ( LAP ), mean central venous pressure ( CVP ), packed cell volume (PCV), total plasma protein (TPP), plasma sodium, potassium and chloride concentrations, and urinary sodium and potassium concentrations.
During halothane anaesthesia there were significant decreases in AP , PCV, TPP, f, and significant increases in arterial and mixed venous oxygen, and glucose concentrations, when compared with conscious control values. When intravenous fluid was administered during anaesthesia, there were significant decreases in temperature, AP , PCV and TPP, with significant increases in PAP , CVP and f, when compared with values during anaesthesia alone. After one hour recovery period from anaesthesia, dogs receiving intravenous fluids had significantly decreased PaO₂ values and significantly increased pH when compared with anaesthesia alone. There was an average urinary excretion of 7 mmol of sodium and 5 mmol of potassium during anaesthesia, and 36 mmol of sodium and 8 mmol potassium during fluid administration.     

Acid‐base and electrolyte balance following administration of three crystalloid solutions in dogs undergoing elective orthopaedic surgery

ObjectiveTo compare acid–base balance and incidence of hyperchloraemic metabolic acidosis following administration of three crystalloid solutions to dogs undergoing anaesthesia for orthopaedic surgery.Study designProspective, randomised, clinical study.AnimalsSixty dogs.MethodsDuring a non–standardised anaesthetic, 0.9% saline (S), Hartmann's solution (H) or a polyionic glucose–free maintenance solution (M) was administered IV at 10 mL kg^?1 hour^?1. Venous blood pH, PCO₂, PCV, total protein, urea, sodium, potassium and chloride concentrations were measured at induction of anaesthesia (T0) and after 2 hours of fluid therapy (T2). Base excess (BE), bicarbonate, corrected chloride concentration (corrCl), osmolality, change in plasma volume (PV) and strong ion gap (SIG) were calculated. Changes in variables within groups (1–sample Student's t–test/Wilcoxon signed rank test) and between groups (1–way anova/Kruskal–Wallis) were assessed. Data are presented as median (interquartile range). Significance was set at p < 0.05.ResultsNo significant differences existed between groups for pH, PCO₂, PCV, total protein, urea, potassium, corrCl, PV and SIG. Potassium significantly increased in all groups. Significant differences existed between groups S and M for BE, sodium, chloride, bicarbonate and osmolality, and between groups H and M for sodium and osmolality. Chloride concentration significantly changed from 116 (114–117) to 117 (116–119) mmol L^?1 in group S, 116 (115–118) to 115 (113–117) mmol L^?1 in group H and 116 (115–118) to 114 (113–118) mmol L^?1 in group M. In groups H and M, sodium and osmolality decreased, and BE and bicarbonate concentration increased significantly. Plasma volume increased by 28 (14–44)%, 25 (5–40)% and 24 (13–33)% in groups S, H and M, respectively.Conclusion and clinical relevanceHyperchloraemic metabolic acidosis did not develop after intraoperative 0.9% saline, Hartmann's solution or maintenance solution at 10 mL kg^?1 hour^?1 for 2 hours in dogs undergoing elective orthopaedic surgery. Bicarbonate and BE increased after Hartmann's and maintenance solutions. Increases in potassium concentration were unexplained.     

Flow-mediated K+ secretion in horses intoxicated with lolitrem B (perennial ryegrass staggers)

AIM: To investigate the effects of lolitrem B intoxication on renal K⁺ secretion in response to increased tubular flow rates.

METHODS: Results are derived from a repeated measure pilot study of seven horses fed non-perennial ryegrass feed for a week prior to exposing them to perennial ryegrass seed and hay that contained an average of 2 ppm lolitrem B. At the end of the control and treatment period frusemide (1 mg/kg I/V) was administered and serial fractional excretion of K⁺(FEK⁺) and fractional excretion of Na⁺(FENa⁺) calculated. Baseline concentration of aldosterone in plasma, serum K⁺concentration and feed K⁺ concentration were also compared.

RESULTS: Key findings included a reduced change in FEK⁺ from 0 to 15 minutes in response to frusemide administration (p=0.022, Wilcoxon signed-rank test) and a reduced baseline concentration of aldosterone in plasma (p=0.022, Wilcoxon signed-rank test) during the treatment period compared with the control.

CONCLUSIONS: Results suggest that lolitrem B intoxication reduced flow-mediated K⁺ secretion and interfered with aldosterone production or secretion. However, further investigation is required to validate these findings and to further elucidate the underlying pathophysiology.

CLINICAL RELEVANCE: Lolitrem B intoxication in horses may cause disruption to electrolyte handling in addition to neurological deficits.     

Some physiological and biochemical effects of acetazolamide in the dog

Acetazolamide was administered at a dose rate of 10 mg/kg intravenously every 8 h to twelve dogs for a period of 7 days. Before administration of the acetazolamide and every second day during the period of administration, values of P_aO₂, P_aCO₂, pH, base excess, bicarbonate, systolic and diastolic arterial pressure, central venous pressure, packed cell volume, haemoglobin and total plasma protein were measured. Plasma concentrations of sodium, potassium, chloride, creatinine, urea, glucose, bilirubin, iron, calcium, phosphate and triglycerides were also determined. These values were also measured in a similar control group of dogs not given acetazolamide. Acetazolamide produced significant elevations in P_aO₂ and chloride values and significant decreases in P_aCO₂, pH, base excess, bicarbonate, potassium and calcium. There were no significant changes in any of the other parameters measured. The non-respiratory acidosis produced by acetazolamide makes it a useful model to enable the investigation of therapeutic regimes for treating acidosis of this type.     

Plasma renin activity and plasma concentrations of aldosterone, cortisol, adrenocorticotropic hormone, and alpha-melanocyte-stimulating hormone in healthy cats

A pathogenetic role of the renin-angiotensin-aldosterone system has been implicated in cats in both systemic arterial hypertension and hypokalemic myopathy. Yet, measurement of plasma aldosterone concentrations (PACs) and plasma renin activity (PRA) has not unequivocally pointed to hyperaldosteronism as a cause of these conditions. To obtain appropriate reference ranges, this study included a large number (130) of healthy house cats of different breeds without a history of recent illness and plasma concentrations of urea and creatinine below the upper limit of the respective reference ranges. In addition, the pituitary-adrenocortical axis was studied by measuring plasma concentrations of adrenocorticotropic hormone (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), and cortisol. Reference ranges for PACs (110-540 pmol/L; 40-195 pg/mL), PRA (60-630 fmol/L/s; 0.3-3 ng/mL/h), and the aldosterone to renin ratio (ARR) (0.3-3.8) were very similar to those established in the same laboratory for humans in a supine position. No breed differences were found. The ARRs in neutered cats were significantly higher than in intact cats, primarily because of low PRA in neutered cats. The ARRs of cats > or = 5 years of age were significantly higher than those of cats < 5 years of age. The plasma concentrations of ACTH, alpha-MSH, and cortisol did not correlate significantly with PAC. Thus, although blood sampling was performed in cats in nonstandardized positions and was associated with a wide variation of stress responses, the references ranges of PAC, PRA, and ARR were similar to the relatively narrow limits established for humans under standardized conditions. The effects of neutering and aging on PRA and ARR warrant further investigation.     

Physiological stimuli of thirst and drinking patterns in ponies

The stimuli that elicit thirst were studied in four ponies. Nineteen hours of water deprivation produced an increase in plasma protein from 67 +/- 0.1 g/litre to 72 +/- 2 g/litre, a mean (+/- se) increase in plasma sodium from 139 +/- 3 to 145 +/- 2 mmol/litre and an increase in plasma osmolality from 297 +/- 1 to 306 +/- 2 mosmol/litre. Undeprived ponies drank 1.5 +/- 0.9 kg/30 mins; 19 h deprived ponies drank 10.2 +/- 2.5 kg/30 mins and corrected the deficits in plasma protein, plasma sodium and plasma osmolality as well as compensating for the water they would have drunk during the deprivation period. In order to determine if an increase in plasma osmolality would stimulate thirst, 250 ml of 15 per cent sodium chloride was infused intravenously. The ponies drank when osmolality increased 3 per cent and when plasma sodium rose from 136 +/- 3 mmol/litre to 143 +/- 3 mmol/litre. Ponies infused with 15 per cent sodium chloride drank 2.9 +/- 0.7 kg; those infused with 0.9 per cent sodium chloride drank 0.7 +/- 0.5 kg. In order to determine if a decrease in plasma volume would stimulate thirst, ponies were injected with 1 or 2 mg/kg bodyweight (bwt) frusemide. Plasma protein rose from 68 +/- 2 g/litre pre-injection to 75 +/- 2 g/litre 1 h after 1 mg/kg bwt frusemide and to 81 +/- 1 g/litre 1 h after 2 mg/kg bwt frusemide.(ABSTRACT TRUNCATED AT 250 WORDS)     

The muscular dystrophic chicken is hypernatremic

1. The E3 ubiquitin protein ligase 1 (WWP1) gene, the mutation of which causes muscular dystrophy in chickens, is expressed not only in the pectoral muscle, but also in a number of tissues such as the kidney. Therefore, this study examined some parameters related to kidney function in muscular dystrophic (MD) chickens.

2. Plasma osmolality, Na⁺ and K⁺ concentrations, aldosterone levels, and the expression of aquaporin (AQP) 2, AQP3, and α subunits of the amiloride-sensitive epithelial sodium channel (αENaC) were analysed in the kidneys of 5-week-old MD chickens and White Leghorn (WL) chickens under physiological conditions or after one day of water deprivation.

3. Plasma osmolality, Na⁺ concentrations, and plasma aldosterone levels were significantly higher in MD chickens than in WL chickens. αENaC mRNA expression levels were lower in MD chickens than in WL chickens. AQP2 and AQP3 mRNA expression levels were similar in the two strains of chickens.

4. Plasma osmolality correlated with aldosterone levels and AQP2 and αENaC mRNA levels in WL chickens. In MD chickens, plasma osmolality correlated with AQP2 mRNA levels, but not with plasma aldosterone or αENaC mRNA levels.

5. These results suggest that neither water reabsorption nor the expression of AQP2 and AQP3 is impaired in MD chickens and that a WWP1 gene mutation may or may not directly induce an abnormality in Na⁺-reabsorption in the kidneys of MD chickens, potentially through αENaC.