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Biomedical subjects

M Vincent

Publications and source records attributed to M Vincent.

At least 379 records · Page 21Linked to original sources

Early increase in phenylethanolamine-N-methyltransferase activity in a new strain of spontaneously hypertensive rats.

By repeated inbreeding, 2 strains of spontaneously hypertensive and normotensive rats have been simultaneously selected. The activities of tyrosine hydroxylase and phenylethanolamine-N-methyltransferase were determined in various central catecholaminergic nuclei (C1, C2, A6 and A9) and in two peripheral tissues (adrenal glands and superior cervical ganglion). These assays were performed on rats belonging to the normotensive or the hypertensive strain at 3 ages which characterize the development of hypertension (5, 9 and 21 weeks). Except for a decrease in the C1 region of 9-week-old rats, no significant change in tyrosine hydroxylase activity occurred in central or peripheral structures of the spontaneously hypertensive rats when compared to the normotensive rats. In contrast, the activity of the phenylethanolamine-N-methyltransferase (PNMT), was increased in the C2 adrenergic group of the medulla oblongata in young spontaneously hypertensive rats: +43% (P less than 0.001) at 5 weeks of age and +32% (P less than 0.001) in 9-week-old rats. However, there was no significant difference between the 21-week-old rats. No modification of the PNMT activity was found in the C1 adrenergic group of the medulla oblongata. PNMT activity was increased significantly in the adrenal glands of 5-week-old hypertensive rats (+22%, P less than 0.001). By 9 weeks, the difference in PNMT activity in the adrenals was no longer significant. Thus, in young rats of the hypertensive strain, there was an increase in the capacity to synthetize adrenaline in the C2 area of the medulla oblongata and in the adrenal glands. While the enzymatic change present in the adrenals seems to be specific to this new strain of hypertensive rats, the elevation of PNMT activity in a specific region of the medulla oblongata (C2 group) is a characteristic common to at least two independently derived strains of genetically hypertensive rats.

Adrenal Glands↗

Solubilization and separation of delta5,3beta-hydroxysteroid dehydrogenase and 3-oxosteroid-delta4-delta5-isomerase from bovine adrenal cortex microsomes.

A physical separation of delta5,3beta-hydroxysteroid dehydrogenase and 3-oxosteroid delta4-delta5-isomerase solubilized from bovine adrenocortical microsomes is described for the first time. The solubilization as well as the separation was carried out with a mixture of a detergent: a substituted betaine (Empigen BB/P) and sodium cholate. This latter detergent protects isomerase from complete inactivation by Empigen and is necessary for the recovery of a significant amount of soluble isomerase. Separation of dehydrogenase and isomerase was successfully accomplished by the use of a DEAE-Biogel A anion-exchanger. Dehydrogenase activity was eluted, while the isomerase was retained. Measurements of dehydrogenase activity with androst-5-en-3beta-ol-17-one, pregnen-3beta-ol-20-one and pregn-5-en-(3beta,17alpha)-diol-20-one and of isomerase activity with androst-5-en-(3,17)-dione and pregn-5-en-(3,20)-dione suggested that more than one isomerase and more than one dehydrogenase form were present.

17-Hydroxysteroid Dehydrogenases↗

Influence of renal nerves on renin secretion in the conscious dog.

In order to evaluate the influence of renal nerves on renin secretion during changes in blood volume, we studied the mean arterial blood pressure (MAP) and the renal venous plasma renin activity (PRA) in 6 conscious dogs having one intact and one denervated kidney. After a passive head-up tilt PRA increased significantly in the vein of the intact kidney while it remained stable in the denervated one. The intravenous injection of Furosemide (3 mg/kg) induced a rapid elevation of PRA in both renal veins. The kinetics of the variations of renin secretion were similar in the two kidneys, but its magnitude was significantly lower in the denervated side. After a slow hemorrhage of 2, 4 and 6 ml/kg, MAP was unchanged and PRA increased in both renal veins but in a significantly lower degree in the denervated side. When blood loss reached 8 ml/kg, MAP decreased and PRA increased identically in the two renal veins. It was concluded that, in conscious dogs, the renal nerves could participate in the rapid adaptations of renin secretion during small changes in the circulating blood volume.

Animals↗

Kinetics of plasma coagulation and lysis I: Basic kinetic model for time course of coagulation-lysis systems and its potential application to clinical studies.

The time courses of coagulation and coagulation-lysis were spectrophotometrically monitored after the addition of thrombin or thrombin-streptokinase to plasma, diluted 1:5 with normal saline, obtained from normal and presumably abnormal subjects. The kinetics of clotting, after an initial lag period of 0.5-1.5 min, demonstrated essentially first-order dependence on the amount of fibrinogen available to form the clot, and the asymptotic absorbance was independent of thrombin concentration. The rate of clotting was a function of added thrombin, and the ratios of the rate constants at 2.5 and 1.25 units of thrombin/ml of undiluted plasma were 1.65 +/- 0.03 SEM. At early times, the coagulation-lysis curve with thrombin-streptokinase could be superimposed on the clotting curve with thrombin alone for a given plasma with minor compensation for variable lag times. Subsequently, the curves diverged; lysis was monitored by the decrease in absorbance of the coagulation-lysis system. The rate of fibrinolysis increased with streptokinase concentration and was a function of the extent of lysis, and it permitted the description of the kinetics of lysis by a pseudoautocatalytic mechanism where the bimolecular rate constant appears proportional to streptokinase concentration. Ranges of clotting and lytic parameters for the plasma of normal subjects are given, and their potential use in diagnosing abnormalities is described.

Blood Coagulation↗

Thyroid function and blood pressure in two new strains of spontaneously hypertensive and normotensive rats.

1. The influence of thryoid function on the development of hypertension was studied in strains of spontaneously hypertensive (SH) and normotensive rats. 2. Surgical thyroidectomy decreased systolic blood pressure more markedly in SH rats than in normotensive rats. The effects of oral administration of 5 and 100 micrograms of thyroxine 24 h-1 100 g-1 were studied in the thyroidectomized animals. In the two strains the blood pressure returned to control levels only after administration of the larger dose. 3. The evolution of body weight, total plasma tri-iodothyronine (T3) and tetraiodothyronine (T4) concentrations were followed as a function of age in SH rats and normotensive rats from 5 to 21 weeks. At each age, SH rats showed significantly larger body weight and decreased T4 concentrations. Plasma T3 in SH rats was lower than in normotensive rats until 15 weeks of age, after which the difference was not significant. At 11 weeks, plasms free T3 and T4 concentrations were slightly lower in SH rats than in normotensive rats. 4. The more marked hypotensive effects of surgical thyroidectomy in SH rats cannot be related to increased thyroid function.

Aging↗

Maternal and fetal plasma renin and dopamine-beta-hydroxylase activities in toxemic pregnancy.

Toxemic and normotensive pregnant women were compared for plasma renin activity (PRA), aldosterone (PA), and dopamine-beta-hydroxylase (DBH). At term, hypertensive patients exhibited higher levels of PRA and PA, but similar levels of DBH, progesterone, and estradiol. Their elevated blood pressure was significantly correlated to their levels of PRA. During the delivery levels of PRA increased significantly in toxemic patients in spontaneous labor. Venous and arterial cord PRA levels were higher in babies born to hypertensive mothers than in babies born to normotensive mothers. Three days postpartum, maternal PRA level was lower than at term. Seven days postpartum, PRA levels remained higher in toxemic than in normal women. Maternal DBH levels did not change during and after delivery. Levels of DBH were undetectable in cord blood. We conclude that the renin-angiotensin system is involved in the pathogenesis of toxemia.

Adult↗

Central cardiovascular effects of morphinomimetic peptides in dogs.

Morphinomimetic peptides were injected into the cisterna magna of chloralosed dogs. Methionine enkepalin (500 microgram/kg i.c.) was found ineffective but beta-endorphin (50 microgram/kg i.c.) induced an initial and transient increase in blood pressure and heart rate followed by a delayed hypotension and bradycardia. The synthetic pentapeptides, [d-ala2]met-enkephalin (500 microgram/kg i.c.), [d-ala2]met-enkephalinamide 500 microgram/kg i.c.) also induced a marked hypotensive, bradycardic and sympatho-inhibitory effect. High doses of naloxone (100 microgram/kg i.v.) were required to antagonize these effects transiently.

Animals↗

Implantable artificial lung. Preliminary report.

The ultimate treatment of chronic respiratory insufficiency is pulmonary replacement by an artificial organ, homologous lung transplantation, or chronic paracorporeal respiratory supplementation. The woven capillary membrane oxygenator appears to be a major development toward implantable artificial organs. The four units tested are made up of screens 3.5 by 4.0 cm. of capillary tubing 0.3 mm. I.D. by 0.64 mm. O.D. assembled into rectangular blocks. Units made up by five, ten, twenty, and forty screens have been assembled and tested according to the protocol suggested by Galletti. The maximum oxygen transfer rate with blood was 48 ml. per minute per square meter. Water carbon dioxide transfer rate was 23.1 ml. per minute per square meter. The pressure drops in the liquid phase were 8.5, 15.3, 13.8, 17.6 mm. Hg at 1 L. per minute flow. These results indicate that the woven capillary membrane lung is an acceptably efficient oxygenator. The characteristics of design and performance suggest that this oxygenator can be made to be implanted into the chest or used as a paracorporeal respiratory assistance device.

Artificial Organs↗

Plasma renin activity as a function of age in two new strains of spontaneously hypertensive and normotensive rats.

1. Strains of spontaneously hypertensive and normotensive rats were selected by repeated inbreeding. 2. Brief ether anesthesia was shown to produce a two- to three-fold increase in plasma renin activity in both strains. 3. Plasma renin activity was significantly higher in young spontaneously hypertensive than in normotensive rats of the same age (5-7 weeks). After the ninth week plasma renin activity decreased and, at week 45, became significantly lower in hypertensive than in normotensive rats. 4. When hypertension was established a significant inverse relationship was found between plasma renin activity and systolic blood pressure in spontaneously hypertensive and in normotensive rats. 5. It seems unlikely that the renin-angiotensin system plays a major role in the maintenance of the established spontaneous hypertension in this strain. However, renin hypersecretion may be important in the early pre-hypertensive stage of genetic hypertension in rats.

Aging↗

A kinetic study of plasma renin and aldosterone during changes of posture in man.

Cardiovascular parameters, hematocrit (Ht), plasma electrolytes, renin activity (PRA) and aldosterone concentration (PAC) were measured in 12 normal human subjects (6 males and 6 females) eating an ad lib diet. At 8 AM, volunteers assumed the following postural changes: 1 hour supine, then 2 hours upright and finally 1 hour supine. Orthostatism induced the following changes: heart rate, systolic and diastolic blood pressure increased immediately; Ht rose significantly at the 5th min in males but not in females; Plasma sodium showed no variations but potassium increased after 30 min; PRA rose significantly at the 5th min and, after 120 min of orthostatism, was found to be 3 times greater than its value after recumbency; and PAC increased significantly at the 15th min and exhibited a plateau 4.5 times its basal values after 90 min of upright posture. When subjects returned to the supine position all the parameters, except PAC decreased. During active orthostatism, a significant correlation was found between PAC and plasma potassium, but correlation was closer between PAC and PRA and between PAC and PRA + potassium. It can be concluded that the renin-angiotensin system is a more potent stimulus for aldosterone secretion than plasma potassium in normal man assuming postural changes. The results presented here can be applied to the development of a short posture test in non-hospitalized patients.

Adult↗