Sodium-, potassium-, chloride-, and bicarbonate-related effects on blood pressure and electrolyte homeostasis in deoxycorticosterone acetate-treated rats

2008 ◽  
Vol 295 (6) ◽  
pp. F1752-F1763 ◽  
Author(s):  
Agata Ziomber ◽  
Agnes Machnik ◽  
Anke Dahlmann ◽  
Peter Dietsch ◽  
Franz-Xaver Beck ◽  
...  

Na+ loading without Cl− fails to increase blood pressure in the DOCA model. We compared the changes in the total body (TB) effective Na+, K+, Cl−, and water (TBW) content as well as in intracellular (ICV) or extracellular (ECV) volume in rats receiving DOCA-NaCl, DOCA-NaHCO3, or DOCA-KHCO3. We divided 42 male rats into 5 groups. Group 1 was untreated, group 2 received 1% NaCl, and groups 3, 4, and 5 were treated with DOCA and received 1% NaCl, 1.44% NaHCO3, or 1.7% KHCO3 to drink. We measured mean arterial blood pressure (MAP) directly after 3 wk. Tissue electrolyte and water content was measured by chemical analysis. Compared with control rats, DOCA-NaCl increased MAP while DOCA-NaHCO3 and DOCA-KHCO3 did not. DOCA-NaCl increased TBNa+ 26% but only moderately increased TBW. DOCA-NaHCO3 led to similar TBNa+ excess, while TBW and ICV, but not ECV, were increased more than in DOCA-NaCl rats. DOCA-KHCO3 did not affect TBNa+ or volume. At a given TB(Na++K+) and TBW, MAP in DOCA-NaCl rats was higher than in control, DOCA-NaHCO3, and DOCA-KHCO3 rats, indicating that hypertension in DOCA-NaCl rats was not dependent on TB(Na++K+) and water mass balance. Skin volume retention was hypertonic compared with serum and paralleled hypertension in DOCA-NaCl rats. These rats had higher TB(Na++K+)-to-TBW ratio in accumulated fluid than DOCA-NaHCO3 rats. DOCA-NaCl rats also had increased intracellular Cl− concentrations in skeletal muscle. We conclude that excessive cellular electrolyte redistribution and/or intracellular Na+ or Cl− accumulation may play an important role in the pathogenesis of salt-sensitive hypertension.

2008 ◽  
Vol 295 (3) ◽  
pp. F837-F842 ◽  
Author(s):  
David L. Mattson ◽  
Melinda R. Dwinell ◽  
Andrew S. Greene ◽  
Anne E. Kwitek ◽  
Richard J. Roman ◽  
...  

This study examined the genetic basis of hypertension and renal disease in Dahl SS/Mcwi (Dahl Salt-Sensitive) rats using a complete chromosome substitution panel of consomic rats in which each of the 20 autosomes and the X and Y chromosomes were individually transferred from the Brown Norway (BN) rat onto the Dahl SS/Mcwi genetic background. Male and female rats of each of the two parental and 22 consomic strains (10–12 rats/group) were fed a high-salt (8.0% NaCl) diet for 3 wk. Mean arterial blood pressure rose by 60 mmHg and urinary protein and albumin excretion increased 3- and 20-fold, respectively, in male SS/Mcwi rats compared with BN controls. Substitution of chromosomes 1, 5, 7, 8, 13, or 18 from the BN onto the SS/Mcwi background attenuated the development of hypertension, proteinuria, and albuminuria in male rats. In female rats, substitution of chromosomes 1 and 5 also decreased blood pressure, protein excretion, and albumin excretion. These studies also identified several chromosomes in male (6, 11, Y) and female ( 4 , 6 , 11 , 19 , 20 ) rats that reduced albuminuria without altering blood pressure. These data indicate that genes contributing to salt-sensitive hypertension are found on multiple chromosomes of the Dahl SS/Mcwi rat. Furthermore, this consomic rat panel provides a stable genetic platform that can facilitate further gene mapping by either linkage studies or the breeding of congenic and subcongenic rats.


2020 ◽  
Vol 48 ◽  
Author(s):  
Bárbara Silva Correia ◽  
Eduardo Raposo Monteiro ◽  
João Victor Barbieri Ferronatto ◽  
Luciana Branquinho Queiroga ◽  
José Ricardo Herrera Becerra

Background: Arterial blood pressure is one of the most commonly variables monitored during anesthetic procedures in veterinary patients. The most reliable method for measuring arterial blood pressure in dogs and cats is the direct (invasive) method. However, the oscillometric method is less complex and more practical for clinical routine in small animals. Nevertheless, oscillometric monitors present great variability in accuracy. The present study aimed to determine the accuracy of the Delta Life DL 1000 oscillometric monitor for measurement of systolic, mean and diastolic blood pressures (SAP, MAP and DAP, respectively) in anesthetized dogs of different weight ranges.Materials, Methods & Results: This study was approved by the Institutional Ethics Committee of Animal Use. Fifteen female dogs of different breeds, weighing 11.6 ± 10.0 kg and with a mean age of 48 ± 51 months were used. All animals were scheduled for elective surgery under general anesthesia in the Institution Veterinary Hospital. Dogs were anesthetized with morphine, propofol and isoflurane and had one 20 or 22 gauge catheter introduced into the dorsal pedal artery for continuous, invasive monitoring of SAP, MAP and DAP. A blood pressure cuff was positioned over the middle third of the radius and connected to Delta Life DL 1000 monitor. Oscillometric readings of SAP, MAP and DAP were registered every 5 minutes, and invasive values were simultaneously recorded. Values obtained with both methods were compared (invasive versus oscillometric) by use of the Bland Altman method to determine the bias, standard deviation of bias and 95% limits of agreement. The percentages of errors between the methods within 10 mmHg and within 20 mmHg were calculated. The results obtained were compared with the criteria from the American College of Veterinary Internal Medicine (ACVIM) for validation of indirect methods of arterial blood pressure measurement. Data were stratified into two groups according to the weight: < 10 kg (Group 1; n = 9); and ≥ 10 kg (Group 2; n = 6). In Group 1, 119 paired measurements were obtained, four of which classified as hypotension (SAP < 90 mmHg), 98 as normotension (SAP from 90 to 140mmHg) and 17 as hypertension (SAP > 140 mmHg). Bias (± SD) values in Group 1 were as follows: SAP, 5.2 ± 18.1 mmHg; MAP, -3.4 ± 17.2 mmHg; and DAP, 12.0 ± 17.5 mmHg. The percentages of errors within 10 mmHg were 40.3% for SAP; 45.4% for MAP and 28.6% for DAP. The percentages of errors within 20 mmHg were 72.3% for SAP, 84.0% for MAP and 68.1% for DAP. In Group 2, 66 paired measurements were obtained, nine of which classified as hypotension, 56 as normotension and one as hypertension. Bias (± SD) in Group 2 were as follows: SAP, 13.6 ± 14.3 mmHg; MAP, -1.1 ± 13.5 mmHg; and DAP, 8.2 ± 16.0 mmHg. The percentages of errors within 10 mmHg were 33.3% for SAP, 77.3% for MAP and 33.3% for DAP. The percentages of errors within 20 mmHg were 65.1% for SAP, 92.4% for MAP and 83.4% for DAP.Discussion: Based on the results of this study and reference criteria from the ACVIM, the Delta Life DL 1000 monitor had a poor accuracy for SAP, MAP and DAP and did not meet the criteria from the ACVIM in anesthetized dogs under 10 kg. Measurements of MAP in dogs ≥ 10 kg met the ACVIM criteria, but measurements of SAP and DAP did not. Based on the findings in this study, the DL 1000 oscillometric monitor is not recommended for blood pressure measurement in anesthetized dogs < 10 kg. In dogs ≥ 10 kg, measurements of MAP yielded acceptable values, but SAP and DAP measurements did not.


2003 ◽  
Vol 12 (3) ◽  
pp. 229-237 ◽  
Author(s):  
Mingyu Liang ◽  
Baozhi Yuan ◽  
Elizabeth Rute ◽  
Andrew S. Greene ◽  
Michael Olivier ◽  
...  

Dahl salt-sensitive SS and consomic, salt-resistant SS-13BN/Mcw rats possess a highly similar genetic background but exhibit substantial differences in blood pressure salt sensitivity. We used cDNA microarrays to examine sequential changes of mRNA expression of ∼2,000 currently known rat genes in the renal medulla (a tissue critical for long-term blood pressure regulation) in SS and SS-13BN/Mcw rats in response to a high-salt diet (16 h, 3 days, or 2 wk). Differentially expressed genes in each between-group comparison were identified based on a threshold determined experimentally using a reference distribution that was constructed by comparing rats within the same group. A difference analysis of 54 microarrays identified 50 genes that exhibited the most distinct temporal patterns of expression between SS and SS-13BN/Mcw rats over the entire time course. Thirty of these genes could be linked to the regulation of arterial blood pressure or renal injury based on their known involvement in functional pathways such as renal tubular transport, metabolism of vasoactive substances, extracellular matrix formation, and apoptosis. Importantly, the majority of the 30 genes exhibited temporal expression patterns that would be expected to lower arterial pressure and reduce renal injury in SS-13BN/Mcw compared with SS rats. The phenotypic impact of the other 20 genes was less clear. These 50 genes are widely distributed on chromosome 13 and several other chromosomes. This suggested that primary genetic defects, although important, are unlikely to be solely responsible for the full manifestation of this type of hypertension and associated injury phenotypes. In summary, the results of this study identified a number of pathways potentially important for the amelioration of hypertension and renal injury in SS-13BN/Mcw rats, and these results generated a series of testable hypotheses related to the role of the renal medulla in the complex mechanism of salt-sensitive hypertension.


Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Mazher Mohammed ◽  
Mona Elgazzaz ◽  
Clara Berdasco ◽  
Eric D Lazartigues

We previously reported that ADAM17 (aka tumor necrosis factor-α convertase) is critical for the development of hypertension in experimental models and patients. Recent studies highlighted that ADAM17’s formation of TNF-α relies on prior maturation of this sheddase, controlled by the rhomboid-like protein 2 (iRhom2) specifically in microglia. Genetic deletion of iRhom2 in mice shows significant attenuation of TNF-α and ADAM17 activity in a tissue specific manner. Here, we hypothesized that silencing iRhom2 activity specifically in the brain would decrease blood pressure (BP) in the DOCA-salt model of hypertension, in mice. Uninephrectomized mice were implanted subcutaneously (sc) with DOCA-pellets (50 mg) and provided with 1% saline in drinking water. In addition, mice were chronically implanted with an icv cannula connected to a sc osmotic minipump for delivery of: (1) iRhom2-siRNA (9.6 μg/kg/day), (2) scrambled siRNA (SCR 0.2 μg/kg/day), (3) ADAM17 antibody (ADAM17-Ab; 23.8 μg/kg/day) or (4) artificial cerebrospinal fluid (aCSF) for 2 weeks while BP was recorded by telemetry. DOCA-salt treatment led to a significant increase in BP in the control groups (SCR: 156 ±3 mmHg and aCSF: 161 ±1 mmHg; n=3/group; p<0.001) compared to baseline values (122 ±2 mmHg; n=12). ICV infusion of iRhom2-siRNA or ADAM17 neutralizing antibody for 2-weeks in DOCA-salt-treated mice resulted in a significant attenuation of BP (iRhom2-siRNA: 152 ±2 mmHg and ADAM17-Ab: 151 ±2 mmHg n=3/group, p<0.001). These data suggest that: 1) Selective silencing of iRhom2 from microglia is as potent as ADAM17 neutralization throughout the brain in lowering BP and 2) iRhom2 is a potential new therapeutic target for the treatment of salt-sensitive hypertension.


2012 ◽  
Author(s):  
Matthew R Rosengart

Cell function and thus life depend on the preservation of several electrochemical gradients. Evolutionary pressures have developed several regulatory mechanisms, the penultimate goal of which is to maintain total body and distribution of each electrolyte within the intracellular and extracellular compartments at concentrations compatible with life. Ultimately, patient survival depends on this balance despite the continual changes imposed by both internal physiologic processes and external stressors. During periods of critical illness, however, these mechanisms can be overwhelmed, necessitating additional support. Indeed, disorders of electrolyte homeostasis are highly prevalent among intensive care unit patients, and severe disturbances are associated with elevated mortality. As has been previously learned, merely normalizing laboratory abnormalities without addressing the underlying pathophysiology does little to improve outcome. Thus, for those providing this care, an in-depth understanding of the biochemistry and physiology of electrolyte disorders and a systematic approach to diagnosis and therapy are complementary components essential for patient survival. This chapter discusses the major electrolytes—sodium, potassium, calcium and phosphate, and magnesium—and covers the hyper- and hypodeficiencies and disturbances for each electrolyte. This review contains 7 Figures, 6 Tables, 5 Etiologic Algorithms, and 106 References.


2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Abimbola Abobarin-Adeagbo ◽  
Andreas Wienke ◽  
Matthias Girndt ◽  
Rainer U. Pliquett

Abstract Background Aim of this study is to investigate a possible association of hypoglycemic episodes and arterial hypertension. We hypothesize that hospitalized insulin-treated diabetes patients with hypertensive crisis have more hypoglycemic episodes than their counterparts without hypertensive crisis on admission. Methods In a prospective, observational cohort study, 65 insulin-treated diabetes patients (type 1, type 2, type 3c) were included in Group 1, when a hypertensive crisis was present, as control patients in Group 2 without hypertensive crisis or hypoglycemia, in Group 3, when a symptomatic hypoglycemia was present on admission. All patients were subjected to open-label continuous glucose monitoring, 24-h blood-pressure- and Holter electrocardiogram recordings, and to laboratory tests including plasma catecholamines. Results 53 patients, thereof 19 Group-1, 19 Group-2, 15 Group-3 patients, completed this study. Group-1 patients had the highest maximum systolic blood pressure, a higher daily cumulative insulin dose at admission, a higher body-mass index, and a higher plasma norepinephrine than control patients of Group 2. Group-3 patients had more documented hypoglycemic episodes (0.8 ± 0.5 per 24 h) than Group-2 patients (0.2 ± 0.3 per 24 h), however, they were not different to the ones in Group-1 patients (0.4 ± 0.4 per 24 h). Plasma norepinephrine and mean arterial blood pressure were higher Group-1 and Group-3 patients than in control patients of Group 2. At discharge, the daily cumulative insulin dose was reduced in Group-1 (− 18.4 ± 24.9 units) and in Group-3 patients (− 18.6 ± 22.7 units), but remained unchanged in Group-2 control patients (− 2.9 ± 15.6 units). Conclusions An association between hypoglycemic events and uncontrolled hypertension was found in this study.


1981 ◽  
Vol 51 (6) ◽  
pp. 1562-1567 ◽  
Author(s):  
J. A. Kitterman ◽  
G. C. Liggins ◽  
J. A. Clements ◽  
G. Campos ◽  
C. H. Lee ◽  
...  

To study their effects on tracheal fluid (TF) production and surfactant flux, we gave 12-h infusions of prostaglandin synthetase inhibitors (PGSI) on 16 occasions to 10 fetal lambs at gestational ages (GA) of 125--141 days. Results were similar with both sodium meclofenamate (13.9 +/- 3.4 mg.kg-1, 12 studies) and indomethacin (33.6 +/- 8.0 mg.kg-1, 4 studies). All studies were done at least 6 days after surgery and 4 days before spontaneous birth. During infusions of PGSI, there were no changes in fetal arterial blood pressure, pH, PaO2, PaCO2, TF production or its concentration of sodium, potassium, and chloride; calcium concentration in TF increased slightly. We expressed tracheal surfactant flux as micrograms.kg-1.h-1 of saturated phosphatidylcholine (SPC). If control SPC flux was less than 5 micrograms.kg-1.h-1 (10 studies at GA of 125--141 days), it did not change during infusion of PGSI; however, if control was greater than 5 micrograms.kg-1.h-1 (6 studies at GA 132--140 days), SPC flux decreased during the infusions in all studies. The results suggest that prostaglandins do not strongly influence TF production up to 4 days before birth and that prostaglandins are involved in the increased flux of surfactant which occurs in late gestation.


1983 ◽  
Vol 244 (1) ◽  
pp. H115-H120 ◽  
Author(s):  
P. C. Houck ◽  
M. J. Fiksen-Olsen ◽  
S. L. Britton ◽  
J. C. Romero

This study was designed to investigate the possible role of angiotensin and vasopressin in the maintenance of arterial blood pressure during acute blockade of the autonomic nervous system. Two groups of eight dogs each were anesthetized with pentobarbital sodium, and autonomic ganglia were blocked with hexamethonium (20 mg/kg). Thirty minutes later group 1 received the vasopressin antagonist 1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid),2-(O-methyl)tyrosine arginine vasopressin (10 micrograms/kg) followed after a 30-min interval by captopril (1 mg/kg). Group 2 received the same drugs, except the order of administration of vasopressin antagonist and captopril was reversed. Vasopressin antagonist during ganglionic blockade (group 2) produced a greater fall in blood pressure than did captopril during ganglionic blockade (group 1). These data indicate that vasopressin plays a greater pressor role than angiotensin in the acute response to ganglionic blockade. Additional studies were performed to determine if the autonomic nervous system alone can support the resting blood pressure in the anesthetized dog. Combined blockade of angiotensin and vasopressin without autonomic blockade produced a significant decrease in blood pressure, suggesting that the autonomic nervous system alone is not able to support the control blood pressure in the anesthetized dog.


1975 ◽  
Vol 53 (5) ◽  
pp. 866-872 ◽  
Author(s):  
George Constantopoulos ◽  
Jacques Genest ◽  
Miyako Kusumoto ◽  
José-Manuel Rojo-Ortega

Deoxycorticosterone pivalate (2.5 mg/kg) given intramuscularly on four occasions 10–15 days apart over a period of 45 days to unilaterally nephrectomized adult male mongrel dogs, receiving as drinking solution 0.9% NaCl in 5% dextrose, resulted in an average sustained rise in the mean arterial blood pressure of 30 mm Hg (1 mm Hg = 133 N/m2) in 60% of the animals. Hypertensive dogs had in their arterial tissues generally more sodium, potassium, magnesium, and calcium than the similarly treated but non-hypertensive dogs, but compared to the tissues of operated untreated or unoperated normotensive dogs, only sodium and calcium were significantly higher. The dogs who were similarly treated but did not develop hypertension had in their arterial tissues less sodium, potassium, and magnesium than operated untreated or unoperated normotensive dogs. Norepinephrine content in the branches of mesenteric arteries of all deoxycorticosterone- and NaCl-treated animals, irrespective of their blood pressure, was significantly lower, and in the myocardium significantly higher, than either the unoperated normotensive or operated but not further treated dogs. It is concluded, therefore, that in deoxycorticosterone + NaCl treatment the dogs which developed hypertension had more arterial sodium, potassium, magnesium, and calcium than those who were similarly treated but remained within the limits of normal blood pressure, and that there was no difference between hypertensive and non-hypertensive dogs in regard to their cardiovascular norepinephrine content.


2020 ◽  
Author(s):  
Abimbola Abobarin-Adeagbo ◽  
Andreas Wienke ◽  
Matthias Girndt ◽  
Rainer U. Pliquett

Abstract Background: Aim of this study is to investigate a possible association of hypoglycemic episodes and arterial hypertension. We hypothesize that hospitalized insulin-treated diabetes patients with hypertensive crisis have more hypoglycemic episodes than their counterparts without hypertensive crisis on admission.Methods: In a prospective, observational cohort study, 65 insulin-treated diabetes patients (type 1, type 2, type 3c) were included in Group 1, when a hypertensive crisis was present, as control patients in Group 2 without hypertensive crisis or hypoglycemia, in Group 3, when a symptomatic hypoglycemia was present on admission. All patients were subjected to open-label continuous flash glucose monitoring, to 24-hour blood-pressure and Holter electrocardiogram recordings, and to laboratory tests including plasma catecholamines. Results: 53 patients, thereof 19 Group-1, 19 Group-2, 15 Group-3 patients, completed this study. Group-1 patients had the highest maximum systolic blood pressure, a higher daily cumulative insulin dose at admission, a higher body-mass index, and a higher plasma norepinephrine than control patients of Group 2. Group-3 patients had more documented hypoglycemic episodes (0.8 ± 0.5 per 24 hours) than Group-2 patients (0.2 ± 0.3 per 24 hours), however, they were not different to the ones in Group-1 patients (0.4 ± 0.4 per 24 hours). Plasma norepinephrine and mean arterial blood pressure were not different between Group-1 and Group-3 patients, though higher than in Group-2 patients. At discharge, the daily cumulative insulin dose was reduced in Group-1 (-18.4 ± 24.9 units) and Group-3 patients (-18.6 ± 22.7 units), but remained unchanged in Group-2 patients (-2.9 ± 15.6 units).Conclusions: An association between hypoglycemic events and uncontrolled hypertension was found in this study.


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