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Biomedical subjects

A Jindra

Publications and source records attributed to A Jindra.

At least 37 records · Page 2Linked to original sources

[Metabolic and humoral characteristics of normotensive offspring in a family with a history of essential hypertension].

Investigations in genetic forms of experimental hypertensions revealed certain haemodynamic, metabolic and humoral abnormalities in experimental animals already during the prehypertensive period. With regard to the obvious ratio of hereditary factors in the pathogenesis of human essential hypertension (EH), the objective of the present study was to test whether also in healthy normotensive subjects with a positive family history of EH some metabolic and humoral deviations can be detected, as compared with offspring from normotensive families. The authors compared therefore selected biochemical and humoral parameters in 20 sons of hypertensive parents (SH) with the findings in 20 sons from normotensive pa families (SN). SH had, as compared with SN, a significantly higher systolic BP (119 +/- 2.59 > 111.0 +/- +/- 2.04 mmHg). The trend of higher basal blood sugar levels 5.03 +/- 0.15 > 4.70 +/- 0.41 mmol/l) and the higher concentration of immunoreactive insulin (81.4 +/- 9.54 > 70.4 +/- after a glucose load +/- 7.78 microU/l) did not reach statistical significance. In SH plasma concentrations of adrenaline, noradrenaline and dopamine were significantly higher as well as the atrial natriuretic factor (11.7 +/- 0.77 > 8.4 +/- 0.40 fmol/ml) and of endothelin (18.2 +/- 1.70 > 12.7 +/- 0.87 fmol/ml). A load of 75 g glucose raised, as expected, the blood sugar level, IRI and C-peptide, but reduced unexpectedly the endothelin concentration in both groups. As to other biochemical parameters (fibrinogen, sodium, potassium, urea, creatinine, uric acid, cholesterol, HDL- and LDL-fractions, triacylglycerols), no significant differences were found between SH and SN. The finding of a raised mass of the left ventricle and certain differences in the diastolic and systolic left ventricular function are discussed in another paper. The results indicate that in young men with a positive family-history of EH already certain haemodynamic, metabolic and humoral deviations exist before clinical manifestation of hypertension which could contribute to later development of EH and its organ complications.

Adult↗

Subcellular distribution of differently glycosylated forms of active and inactive renin in rat kidney: effect of sodium depletion and captopril treatment.

Distribution of differently glycosylated forms of active and inactive renin was investigated in fractions prepared by discontinuous density gradient centrifugation of rat kidney cortex homogenate. Concanavalin A (con A) chromatography separated active and inactive renin into three differently glycosylated forms in both cytosol and granule fractions: a minor con A unbound form (I), a loosely bound form (II), and the most predominant tightly bound form (III). After a long-term stimulation of renin synthesis and secretion by sodium depletion and captopril treatment the relative proportion of active renins I and II in granules significantly increased, while that of active renin III decreased. The relative proportion of inactive renins I and II in granule compared to cytosol fractions was significantly higher and that of inactive renin III was lower. The results indicate that glycosylation might have some relation to the rate of sorting of prorenin into the granules, or of its processing within granules. Alternatively, it might influence the rate of inactive renin release via the constitutive pathway.

Animals↗

Investigation of human and rat inactive renin in plasma and kidney.

Under an initial interval of immobilization stress in rats, reciprocal changes of plasma active and inactive renin were observed, suggesting activation of circulating inactive renin. Molecular weight (MW) studies revealed that this activation might proceed via a MW shift from inactive renin with MW of 50,000 to active renin of MW 43,000. In a later interval of stress, under stimulated renin secretion, a lower MW form (38,000) of active renin was released into the circulation. This MW is close to that of active renin (39,000) found in rat kidney renin granules. In renin granules, equilibrated in fractions of 1.6 and 1.7 mol/L sucrose in discontinuous density gradient, trypsin-activatable renin activity formed 36 and 16% of total activity, respectively. In humans, under acute bicycle exercise, a lower MW form (39,000) of active renin was released into the circulation, while the content of inactive renin with MW in the range of 51,000-58,000 and at 47,000 did not substantially change. There was a slight decrease in circulating inactive renin passing through the kidney. The data suggest that, at least in rats, in vivo pathways for activation of inactive renin might exist, other than that proceeding before secretion from renin granules. Under the conditions of increased renin secretion, a lower MW form of active renin is mainly released into the circulation in both rats and humans.

Adrenal Medulla↗

Relationship between plasma catecholamines and the renin-aldosterone system during exercise in normal and essential hypertensive subjects.

Interrelations were investigated between blood pressure, plasma epinephrine (E), norepinephrine (NE), dopamine (D), aldosterone, cortisol concentrations, active and inactive plasma renin activity (PRA), and age in 21 normotensive subjects (aged 20-60 years) and in 25 patients (aged 20-63 years) with essential hypertension (EH). These parameters were measured at rest and during exercise on a bicycle ergometer. In normotensive subjects basal and exercise-stimulated levels of plasma NE increased with age which was not observed in EH. In hypertensive patients there was a higher plasma D concentration under the exercise as compared with normotensive controls. In the normotensives, basal active PRA was inversely related to age (p less than 0.05), and during initial 8 min of exercise active PRA significantly correlated with plasma E and plasma NE. Moreover, absolute changes from basal to acutely stimulated values of active PRA were directly related to the changes of plasma E and NE (p less than 0.001). In hypertensive patients these relationships were not found. However, in the hypertensives there were significant positive correlations between the increases of active PRA, plasma E, plasma NE on the one hand and their respective basal values on the other hand. The results indicate very strong functional relationship between the sympathetic-adrenomedullary and renin-angiotensin systems during initial interval of acute stimulation in normotensive subjects. Essential hypertension is not a pathophysiologically homogenous disease with respect to reactivity and interaction of plasma catecholamines and PRA. Separate regulatory pathways exist for plasma active and inactive renin. During short-time exercise aldosterone secretion is related rather to the renin-angiotensin system than to the hypothalamic-pituitary axis.

Adult↗

Plasma catecholamines do not participate in pituitary-adrenal activation by immobilization stress in rats with transection of nerve fibers to the median eminence.

The effect of immobilization stress was studied in rats in which the CRF and arginine vasopressin-containing innervation of the median eminence was destroyed by an anterolateral cut (ALC) around the medial basal hypothalamus. One week after surgery, the rats with ALC were subjected to immobilization and they showed a normal rise in plasma corticosterone, a smaller than normal rise of plasma ACTH, and an increased response of plasma epinephrine and norepinephrine. When in rats with an ALC the response of plasma catecholamines was prevented by guanethidine pretreatment and adrenal enucleation the small rise in plasma ACTH was unchanged during immobilization. In addition, the plasma corticosterone and ACTH rises during immobilization in the rats with ALC were not influenced by prior treatment with phentolamine (2.5 mg/kg ip) or propranolol (2.5 mg/kg ip). These findings suggest that the large rises in plasma epinephrine and norepinephrine levels during immobilization do not contribute to changes in plasma ACTH or corticosterone levels when hypothalamic regulation via CRF and/or arginine vasopressin is interrupted by ALC.

Adrenal Glands↗

Purification of pepsins and cathepsin D by affinity chromatography on Sepharose 4B with an immobilized synthetic inhibitor.

Val-D-Leu-Pro-Phe-Phe-Val-D-Leu, a specific inhibitor of aspartate proteinases of the pepsin type, was synthesized. Its bonding to activated 6-aminohexanoic acid-Sepharose 4B afforded an affinity support suitable for the purification of human, porcine, and chicken pepsin, human gastricsin, and bovine cathepsin D. These enzymes bind to the support over the pH range 2-5 at 0-1.5 M concentration of NaCl. A buffer at pH greater than or equal to 6, low ionic strength, and containing 20% dioxane can serve as a general desorption agent. The proteinases were isolated from the crude extracts by a single-step procedure in a high degree of purity and in yields exceeding 70%; human pepsin, however, was not separated from human gastricsin. The support does not show any binding capacity for rat plasma renin at pH 7.4 and for some cysteine endopeptidases (cathepsin B, H, and L) at pH 3-5. The cathepsin D preparations isolated by affinity chromatography on the new support and on pepstatin-Sepharose were of the same degree of purity as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, N-terminal amino acid sequences, and specific activity.

Animals↗

Stress-induced activation of inactive renin. Molecular weight aspects.

We have investigated the response of plasma renin activity (PRA), total, active, and inactive plasma renin concentration (PRC) to immobilization stress in rats. A great increase of PRA was already found after 5 min of immobilization. In contrast, total PRC was elevated only after 1 h of stress. During the initial 15 min, the increase of active PRC was quantitatively matched by the decrease of inactive PRC. This suggests that the initial very rapid response of the plasma renin-angiotensin system to immobilization stress is facilitated by the activation of inactive renin. To get more information about this in vivo activation process, we performed gel filtration of control, acid-treated control, and plasma from 15-min immobilized rats. In the control plasma, two peaks with renin-like activity corresponded to molecular weights of approximately 43,000 and 36,000. Acid-activatable renin was eluted at four molecular weights: 50,000, 58,000, 72,000, and 85,000. In acid-treated control plasma, the peak at 85,000 was decreased and the peak at 43,000 was increased. In plasma from 15-min immobilized rats, the inactive renin of Mr 50,000 was suppressed more than that of 85,000 while the level of active renin, Mr 43,000, was much higher than in controls. The results indicate that stress-induced in vivo activation of inactive renin does not proceed by the same mechanism as in vitro acid-activation.

Animals↗

The role played by hormonal factors in the rapid activation of liver glycogen phosphorylase in traumatized rats.

In adult male SPF rats anaesthetized with pentobarbital and subjected to traumatization in revolving Noble-Collip drums for 2 min (= 120 revolutions) maximal increases of liver glycogen phosphorylase activity were observed. In experiments on rats with permanent arterial catheters for blood sampling no posttraumatic increase of plasma norepinephrine and an only slight increase of plasma epinephrine was observed if the animals were traumatized under anaesthesia, in contrast to the considerable increases in the plasma level of both hormones in rats subjected to the injury without anaesthesia. Time and extent of the phosphorylase response of anaesthetized rats after trauma were compared with changes in enzyme activity after i.v. administration of exogenous epinephrine or glucagon. A nearly maximal response after 1 microgram kg-1 epinephrine was present within 1 min, whereas after 0.1 micrograms kg-1 of glucagon there was comparable phosphorylase activation 2 min after administration of the hormone. The plasma renin-angiotensin activity was not increased after injury for 2 min under anaesthesia so that only the increase in plasma vasopressin fitted in with the criteria for possible activators of phosphorylase. An additional role of glucagon also cannot be excluded on the basis of data obtained by the present authors. The increase of phosphorylase activity in this type of stress is ensured by several mechanisms. Moreover, the high effectivity of these hormonal factors in evoking the phosphorylase response even without major activation of the sympathicoadrenal system is underlined.

Anesthesia↗

Effect of chloro- and bromo-derivatives of isocrotonic acid of bioenergetic processes in Ehrlich ascites cells and isolated mitochondria.

The effect of nine chloro- and bromoderivatives of isocrotonic acid on some bioenergetic processes in both Ehrlich ascites cells and isolated rat liver mitochondria has been investigated. Substances studied in the concentration range 25--200 microM significantly inhibited incorporation of both 14C-adenine and 14C-valine into acid-insoluble material of Ehrlich ascites cells. The rate of 14C-precursors incorporation being directly related to the concentration of the inhibitor. Gamma,gamma-bis-4-ethylphenyl-alpha,beta-dichloroisocrotonic acid fully inhibits both aerobic glucose utilization and lactic acid formation at 200 microM concentration. At lower concentrations, however, glycolysis is stimulated. Maximal stimulation of rat liver mitochondrial respiration in state 4 with succinate as substrate was reached at concentrations as low as 10 microM. On the other hand, these substances were able to release by the oligomycin inhibited respiration of rat liver mitochondria. Our data suggest that cytotoxic and cancerostatic action of isocrotonic acid derivatives lies primarily in the exclusion of key processes in the energy metabolism of Ehrlich ascites cells and isolated mitochondria.

Animals↗