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M A Devynck

Publications and source records attributed to M A Devynck.

197 records · Page 11Linked to original sources

Angiotensin-induced variations of receptors in rat uterine membranes.

1. 3H-labelled angiotensin II specfically binds to plasma membranes of rat uterine smooth muscle cells. Two classes of binding sites differing in their affinity for the hormone were demonstrated. The high-affinity binding sites (KD 29 degrees C approximately 2.0 X 10(-8) mol/l) probably correspond to the receptors involved in the biological response. 2. Bilateral nephrectomy significantly increases the concentration of 3H-labelled angiotensin-binding sites, a phenomenon which seems unrelated to the freeing of receptor sites secondary to the suppression of plasma angiotensin. This phenomenon may be responsible for the specific hypersensitivity in vitro to angiotensin of uteri excised in anephric rats as compared with normal rats. 3. Angiotensin II infusion in nephrectomized rats reduced the concentration of 3H-labelled angiotensin-binding sites. 4. It is suggested that the angiotensin receptor concentration is regulated by the concentration of circulating angiotensin.

Angiotensin II↗

Sodium intake and plasma angiotensin level as modulators of adrenal and uterine angiotensin II receptors in the rat.

Angiotensin II receptors from rat adrenal cortex and myometrium were studied with the use of tritiated angiotensin under conditions where the sensitivity of the target organs for angiotensin II is modified. Sodium status was found to modulate the number of angiotensin receptors both in adrenal gland and uterus. In both target tissues low Na+ diet increases the number of receptors, while a high Na+ diet results in an increase in uterine receptors without modifying adrenal cortical receptors. However, a more markedly positive sodium balance, such as that observed in deoxycorticosterone acetate (DOCA) hypertension and in one-kidney Goldblatt hypertension, resulted in a reduction of the adrenocortical angiotensin II binding capacity. The endogenous angiotensin II level may also regulate the number of receptor sites as demonstrated by an increased number of receptors after suppression of circulating angiotensin II. It is proposed that the number of angiotensin II receptors is determined by the combined influences of sodium status and angiotensin II concentration. Some changes in the sensitivity of the target organ can be secondary to variations in the number of angiotensin receptors. However, others cannot be so explained and stem, therefore, from events occurring beyond the hormone-receptor interaction.

Adrenal Glands↗

Quantitative changes in cardiac Na+, K+ -adenosine triphosphatase of spontaneously hypertensive rats.

Sodium pumps of cardiac plasma membranes were studied in young, spontaneously hypertensive rats (SHR) and in their normotensive controls (Wistar-Kyoto; WKY) using the two following methods. The enzymatic activity and its sensitivity to ouabain were measured as the Na+, K+ -dependent ATP hydrolysis, and the number of pumps was estimated by [3H] ouabain binding. The main results of this study were the observations that (a) concentrations of ouabain as low as 10(-10) M inhibited 10-15% of the enzyme activity in both strains; (b) Na+, K+- adenosine triphosphatase (ATPase) activity in membranes from SHR was double that in membranes from WKY (16.5 +/- 3.2 mumol Pi/h/mg protein vs. 8.2 +/- 1.2 mumol Pi/h/mg protein for 10(-7) M ouabain; p less than 0.01); (c) sensitivity to three different cardiac glycosides, ouabain, digoxin, and digitoxigenin, was identical in SHR and WKY vesicles; and (d) the binding capacity of [3H] ouabain was significantly higher in SHR than in WKY vesicles, but the dissociation constant (KD) did not appear to differ between the two substrains. These studies, performed on 3-week-old rats before the appearance of hypertension, showed, on the one hand, the existence of a Na+, K+ -ATPase of very high affinity in the rat heart, and, on the other, that cardiac sarcolemmal membranes from SHR had a greater number of sodium pumps than those from WKY and thus a greater ability to extrude sodium.

Animals↗

Analysis of calcium handling in erythrocyte membranes of genetically hypertensive rats.

Calcium handling by erythrocyte membranes was compared in genetically hypertensive (SHR) and normotensive (WKR) rats by direct measurement of calcium binding, passive influx, and adenosine triphosphate (ATP)-dependent extrusion. The SHR erythrocyte membranes exhibited the following abnormalities: 1) the binding capacity of the high affinity Ca2+-binding sites located on the inner side of the membrane was 0.84 +/- 0.07 nmole/mg protein compared with 1.17 +/- 0.08 nmole/mg protein in WKR, 2) ATP-dependent Ca2+ extrusion, measured as the Ca2+ influx into inside-out vesicles, was also lower than the WKR, as was the La3+ -sensitive, Ca2+ -dependent hydrolysis, indicating reduced activity of the calcium pump; 3) the passive calcium influx into ATP-depleted red blood cells was slightly accelerated. these abnormalities in Ca2+ binding and transport probably enhanced intracellular Ca2+ concentration, and were observed under both prehypertensive an hypertensive conditions, in 3-week-old and adult SHR respectively. Similar membrane defects in excitable cells may help to explain the pathogenesis of hypertension, since they may increase vascular tone and/or catecholamine release.

Adenosine Triphosphatases↗

Specific changes in hypothalamic alpha-adrenoceptors in young spontaneously hypertensive rats.

Changes in the activity of hypothalamic and brain-stem adrenergic neurons have been reported in young spontaneously hypertensive rats (SHR) prior to the development of hypertension. We have measured central alpha- and beta-adrenoceptor concentrations in 4-week-old SHR and Wistar-Kyoto (WKY) controls by direct radioligand binding studies using [3H]prazosin (alpha 1), [3H]clonidine (alpha 2), and [125I]iodohydroxybenzlpindolol (beta). The concentration of alpha 2-adrenoceptors was significantly elevated in the hypothalamus of the SHR, 156.9 +/- 10.4 compared with WKY, 119.4 +/- 10.0 fmole/mg protein (n = 7, mean +/- SEM, p less than 0.0125). Alpha 2-adrenoceptor concentrations in both the brain stem and cerebral cortex were similar in the two groups of animals. The increase in hypothalamic adrenoceptors was specific for alpha 2-adrenoceptors, since similar concentrations of alpha 2- and beta-adrenoceptors were found in this region.

Animals↗

Plasma protein changes in primary hypertension in humans and rats.

To determine whether plasma protein changes may be associated with primary hypertension, we analyzed plasma proteins from essential hypertensive (EHT) patients and genetically hypertensive rats using two-dimensional electrophoresis. An additional plasma protein, having a molecular weight of 13,000 daltons and an isoelectric point of 4.5, was found in 82% of the patients with borderline or moderate hypertension (n = 29) and in all permanently hypertensive patients (n = 12). This protein was detected in 36% of normotensive (NT) subjects (n = 50). In the latter, the influence of family history, sex, and secondary hypertension were studied. Plasma proteins were also studied in spontaneously hypertensive rats (SHR). In all plasma from young male (n = 10) and female (n = 6) SHR, two additional proteins (molecular weight = 16,000 daltons, pHi = 4.7 and 5.1) were detectable. These plasma proteins were not detectable in male Wistar Kyoto rats (WKY) and in 50% of female WKY, and their frequency was 10% (n = 10) and 0% (n = 3) in normal male WKY and in male WKY rendered hypertensive by methylprednisolone, respectively. We conclude that these alterations of plasma proteins may be considered a biochemical feature of primary hypertension.

Adolescent↗

[Inhibitory effect of noradrenaline on dopamine release from the hypothalamus of the rat].

1. The release of dopamine from the anterior hypothalamic/preoptic region of the anesthetized and artificially ventilated rats was investigated in vivo using a superfusion technique with a push-pull cannula. L-DOPA and pargyline were added to synthetic cerebrospinal fluid superfusing the area. Dopamine was measured by electrochemical detection after separation by liquid chromatography. Dopamine release rapidly reached stable values after the addition of L-DOPA. 2. Serotonin (10-6M) slightly inhibited dopamine release. Other experiments are necessary to characterize this interaction. 3. Lesions of the ventral noradrenergic bundle by a knife cut significantly increased the release of dopamine. 4. This lesion prolonged the apparent half-life of noradrenaline in the AH/PO. 5. Low concentration (10-7M) of noradrenaline inhibited dopamine release when a lesion was performed prior to the superfusion. 6. These data are compatible with a tonic noradrenergic mechanism mediating an inhibitory control of dopamine release in the AH/PO.

Animals↗

[Catecholamine determination in plasma using high performance liquid chromatography with electrochemical detection. Application to a rapid diagnosis of phaeochromocytoma (author's transl)].

The advantages of this technique are rapidity (performed in less than twenty minutes), reproductibilitky, and low cost. Chemical manipulation of plasma is unnecessary to diagnose phaeochromocytoma as shown in two examples. We propose therefore introduction of this technique in clinical investigation of hypertensive patients.

Adrenal Gland Neoplasms↗