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Biomedical subjects

R Boucher

Publications and source records attributed to R Boucher.

At least 91 records · Page 5Linked to original sources

Effect of estrogens on apomorphine-induced circling behavior in the rat.

The effect of administration of estrogens parenterally for 1 week was tested on apomorphine-induced circling in a group of castrated female rats with a lesion of the left entopednucluar nucleus. We observed a significant decrease in the number of turns per minute in estrogen-treated animals as compared with controls. Our tentative explanation is that estrogens decrease the sensitivity of dopamine receptors in the striatum.

Animals↗

Static lung mechanics of intact and excised rhesus monkey lungs and lobes.

Subdivisions of lung volume and pressure-volume (PV) curves of the lung and chest wall (CW) were measured in 12 rhesus monkeys (Macacca mulatta) under pentobarbital anesthesia. In addition, volumes and PV curves were obtained on the excised lungs and lobes of 12 cynomolgus monkeys (M. fasicularis). Boyle's law was used to determine functional residual capacity (FRC) in the intact animals and water displacement to determine minimal volume (MV) in the excised lungs. Total lung capacity (TLC = lung volume at a transpulmonary pressure of 30 cmH2O) was similar in vivo and in vitro (90 + 83 ml/kg) but residual volume (RV = volume at airway pressure of -50 cmH2O) and MV differed markedly (16.5 + 5.9 ml/kg). In the intact animals a very stiff CW appeared to determine RV, whereas airway closure determined MV in excised lungs. PV curves of upper and lower lobes were not different when expressed as %TLC but when expressed as milliliters of gas per gram of lung, the upper lobes contained significantly more gas per unit weight.

Animals↗

Airway responses to histamine and methocholine in Ascaris suum-allergic rhesus monkeys.

We performed dose-response curves to inhaled histamine (H) and methacholine (MC) in a group of eight rhesus monkeys, with and without natural allergy to Ascaris suum antigen (AA). The animals were anesthetized with pentobarbital sodium, 25 mg/kg im and studied in a volume-displacement body plethysmograph. The dose of H or MC producing a 50% increase in pulmonary resistance (RL) was used to determine sensitivity to these agents and the increase in RL at a given dose was employed as a measure of reactivity. Sensitivity and reactivity to H and MC were then compared with AA responsiveness. A wide range of responses was observed but allergic animals were not more sensitive or reactive to H or MC than nonallergic animals. In addition, we studied the changes in breathing pattern that occurred during the inhalation of AA, H, and MC in four AA-sensitive animals. AA and H produced rapid shallow breathing within 30 s of starting inhalation, but MC, despite causing an equal degree of bronchoconstriction, did not produce alterations in breathing pattern.

Aerosols↗

Selective hypopituitarism with severe hyponatremia and secondary hyporeninism.

A female patient presenting clinically a severe hyponatremia was found to have a selective hypopituitarism with predominant ACTH and partial FSH, LH, and GH deficiency as well as a suppression of plasma renin activity and aldosterone. The adrenal cortex responded well in cortisol increase to ACTH infusion and in plasma aldosterone increase to angiotensin II infusion. The patient had pressor hyperreactivity to angiotensin II. The hyponatremia was caused by a negative sodium balance induced by excessive urinary loss which remained unaffected by mineralocorticoid treatment. Substitution doses of cortisol, however, corrected the disturbance with an increase in plasma renin activity and improvement in the sodium balance. The data are interpreted as indicating a direct or indirect regulatory (permissive?) effect of low doses of cortisol on plasma renin activity correcting the underlying disturbance--the secondary hyporeninism.

Adrenocorticotropic Hormone↗

Tonin--angiotensin II system in hypertension.

1. A single intravenous administration of rabbit tonin antiserum into one-kidney one-clip hypertensive rats restored blood pressure to normal in seven out of ten animals. There was little change in blood pressure in two-kidney one-clip hypertensive, uninephrectomized or sham-operated rats. 2. Infusion of tonin in control rats did not modify arterial blood pressure. However, in indomethacin salt-treated rats a marked increase in arterial blood pressure was observed under tonin infusion. 3. Plasma tonin activity was significantly increased in human essential and renovascular hypertension. 4. These findings strongly suggest that tonin is important in the maintenance of high blood pressure. However, other factors (possibly prostaglandins and sodium) have to be modified in order to activate the tonin--angiotensin II system.

Angiotensin II↗

Renal vein plasma adenosine 3',5'-cyclic monophosphate in renovascular hypertension.

The concentration of plasma adenosine 3',5'-cyclic monophosphate (cyclic AMP) and plasma renin activity (PRA) were measured concomitantly in blood from both renal veins and in arterial blood in 22 hypertensive patients. In the nine patients with true renovascular hypertension the concentration of plasma cyclic AMP was greater in the venous effluent of the kidney affected by the renal artery stenosis than in that of the unaffected or less affected kidney. The arteriovenous difference in cyclic AMP concentration was less on the affected side in all but one patient. The arteriovenous differences in PRA identified the affected kidney as the source of hyper-reninemia and showed that renin release from the other kidney was suppressed. In the 13 patients with hypertension associated with but unrelated to renal artery stenosis there were no consistent patterns of cyclic AMP concentration or PRA in the venous effluent of the kidneys or of their arteriovenous differences. In renovascular hypertension the venous effluent of the kidney affected by renal artery stenosis contains not only more renin but also more cyclic AMP, owing to either increased cyclic AMP production or decreased excretion or extraction of cyclic AMP by the affected kidney. This unilateral increase in cyclic AMP concentration may become a complementary diagnostic feature of true renovascular hypertension.

Cyclic AMP↗

Effects of 1694 and other dopaminergic agents on circling behavior.

One hour after the administration of 40 mg/kg of amineptine chlorydrate (1694) the HVA concentration in the striatum was increased but the concentrations of DA, NA, 5HT and 5-HIAA in the striatum, cortex, thalamus-hypothalamus and pons-midbrain of rats were not significantly altered. Unilateral lesioning at the level of the entopeduncular nucleus in cats and rats resulted in spontaneously occurring ipsiversive circling behavior in the two species. However circling was more sustained in cats than in rats. Apomorphine, d-amphetamine, methamphetamine, L-dopa and piribedil (ET-495) exaggerated the ipsiversive circling. 1694 (amineptine chlorydrate), a new agent, was comparatively more active than L-dopa and ET-495 and less active than apomorphine, d-amphetamine and methamphetamine. Although in higher doses (30--40 mg/kg), 1694 caused increased exploratory activity it was not associated with any stereotypy. Its biochemical and pharmacological effects are comparable to those of d-amphetamine and methamphetamine. Removal of the contralateral (with respect to the side of the entopeduncular lesion) motor cortex in the lesioned cat abolished spontaneous and drug-induced circling movements. The results of this and of previous studies support the idea that these dopaminergic agents act on the striopallidal system of the intact side which is no longer properly counterbalanced by the corresponding system of the lesioned side. Although this experimental model is useful to determine the degree of dopaminergic activity of various chemical agents it does not duplicate the motor disorders encountered in parkinsonism which are associated with a decreased concentration of dopamine.

Animals↗

Morphological characteristics of acetylcholinesterase-containing neurons in the CNS of DFP-treated monkeys. Part 2. Diencephalic and medial telencephalic structures.

The distribution and morphological characteristics of neurons containing acetylcholinesterase (AChE, EC 3.1.1.7.) in diencephalic and medial telencephalic structures of the rhesus monkey (Macaca mulatta) were studied by means of a pharmaco-histochemical method that involves staining for AChE (Karnovsky-Roots' procedure) at various times after the administration of di-isopropylfluorophosphate (DFP). At medial telencephalic levels, numerous, mostly multipolar, AChE-containing neurons of medium to large size are present in the bed nucleus of the anterior commissure, in the ascending division of the nucleus of the diagonal band of Broca, and in the so-called "substantia innominata". This last structure is composed of medial and lateral AChE cell groups that extend caudad, beneath the lenticular nucleus, for a considerable distance. The AChE neurons lying within the substantia innominata correspond, at least in part, to the basal nucleus of Meynert. Most neurons of the olfactory tubercle are devoid of AChE but lie within a lightly-stained AChE background. In addition, clusters of amorphous and highly reactive AChE material are found within the islands of Cajella and along the ventromedial edge of the olfactory tubercle. At the level of the thalamus, the strongest AChE staining is seen in the periokarya of the anterior dorsal nucleus and of most nuclei located within the fibrous or lamellar thalamic structures--i.e., the reticular nucleus, the intralaminar nuclei, and the midline nuclei except nuclei parataenialis and reuniens. In most of these nuclei the neuronal somata are of medium size and stain moderately for AChE. Their proximal processes are either lightly stained or devoid of AChE. At the level of the hypothalamus of the monkey, intense AChE staining can be seen within the neuronal somata of the supraoptic and paraventrivular nuclei. In the paraventricular necleus, the AChE-positive perikarya are of medium size and have numerous AChE-containing processes. Moderately reactive AChE neurons of smaller size with unstained processes are also present in the paraventricular nucleus. Most perikarya of the main rostral portion of the supraoptic nucleus are moderately stained for AChE, are closely packed, and their processes are difficult to discern. The main cellular aggregate of the supraoptic nucleus extends caudad and is composed of a large group of moderately to intensely stained neurons lying along the optic tract and which constitute the caudal, or infundibular, portion of the supraoptic nucleus. Other moderately to intensely stained AChE neurons were found in the lateral and perifornical areas and most particularly in the dorsal hypothalamic area. These neurons are of medium size and mostly multipolar. Moderately stained AChE neurons were also observed in the supramammillary nucleus, as well as those of the acruate nucleus, however, are only weakly reactive. The median eminence and most neurons of the ventromedial nucleus of the monkey hypothalamus are virtually devoid of AChE...

Acetylcholinesterase↗

Potentiation of pressor effects of noradrenaline and potassium ions in the rat mesenteric arteries by physiological concentrations of angiotensin II: effects of prostaglandin E2 and cortisol.

1. In the perfused rat mesenteric vascular bed, the effects of angiotensin II, cortisol and prostaglandin E2 on the vascular responses to noradrenaline or potassium chloride were studied. 2. Angiotensin II in subpressor concentrations potentiated the vasoconstrictor response to noradrenaline and potassium chloride. This effect of angiotensin II was inhibited in the presence of indomethacin and prostaglandin E2. 3. Cortisol in physiological concentrations inhibited the potentiating effect of angiotensin II. 4. Prostaglandin E2 enhanced the vasoconstrictor response to noradrenaline. This effect was not abolished by cortisol. 5. These results suggest that some actions of angiotensin II and cortisol in vivo are mediated by the regulation of prostaglandin synthesis or release.

Angiotensin II↗

Week long partial pulmonary bypass with an artificial lung pumped by the right ventricle.

Extracorporeal pumping PA-LA perfusions were carried out for 24 hrs in 5 awake, alert lambs by cannulating the main PA and the LA with large bore polyurethane cannulae. A mean of 42% of the basal cardiac was pumped through the membrane lung. When the PA occluder cuff was progressively inflated, up to 80% of the basal cardiac output was diverted to the extracorporeal circuit for short periods. Hemothorax remained a significant problem. Three lambs were electively perfused 12 hrs, 36 hrs, and 8 days without a roller pump, using a low resistance spiral coil membrane lung pumped by the RV. By inflating the occluder cuff, a mean of 55% of basal cardiac output was pumped by the RV through the membrane lung. The 8 day bypass lamb remained healthy and active without any bleeding or gross pathology. We did not observe air emboli, thromboemboli or gross infections in either group. We believe that such a mode of cannulation will eventually allow long-term perfusion of a low resistance membrane oxygenator driven directly by the RV.

Animals↗

Effect in vivo of beta-adrenergic stimulation, angiotensin II, dibutyryl cyclic AMP, and theophylline on tonin concentration in rat saliva and submaxillary gland.

Tonin (an enzyme present in rat submaxillary gland and saliva) has previously been shown to be able, unlike renin and reninlike substances, to release angiotensin II either directly by acting on an appropriate substrate or from angiotensin I. The administration of a beta-adrenergic drug, isoproterenol, produces a rise of tonin concentration in saliva without affecting its concentration in the submaxillary gland. Prior administration of a beta blocker, propranolol, partially prevents this effect. The administration of theophylline increases the tonin concentration in both saliva and the submaxillary gland, whereas dibutyryl cyclic AMP increases tonin concentration in the former. These results suggest that beta-adrenergic stimulation enhances both tonin release into the saliva and tonin synthesis in the submaxillary gland, and that these effects might be mediated by cyclic AMP. Infusion of angiotensin II blocked the stimulatory effect of isoproterenol on salivary tonin. 1Sar-8Ile-angiotensin II is both a weak antagonist of angiotensin II in this respect and a strong agonist in terms of blocking the effect of isoproterenol another role mirrored in other physiological mechanisms of derivatives of angiotensin II.

Angiotensin II↗

Dependence of tonin activity in rat submaxillary gland on growth hormone and testosterone.

Tonin, an enzyme present in rat submaxillary gland, converts angiotensin I to angiotensin II and is able to form angiotensin II directly from renin substrates. This enzyme was previously shown to be different from renin, tissue isorenins, and angiotensin I converting enzyme. The specific activity of tonin in rat submaxillary gland increases with the age of the animal and is much higher in male than in female rats; this sex difference is apparent from 60 to 70 days of age. There is a sharp drop of tonin activity in hypophysectomized animals, whereas adrenalectomy, thyroidectomy, and gonadectomy have have little effect. The marked increase in tonin activity was observed in animals bearing MtT-F4 transplantable tumors known to produce ACTH, prolactin, and growth hormone. Tonin specific activity in hypophysectomized male rats is restored to control levels by combined treatment with growth hormone and testosterone. Prolactin alone or in combination with testosterone, as well as transplanted pituitaries, has no effect in hypophysectomized animals. There is a significant specific binding of 125I-labeled growth hormone to isolated membranes of rat submaxillary gland.

Age Factors↗

Catecholamines, cyclic AMP and renin in two contrasting forms of essential hypertension.

Essential hypertension (EH) can be subdivided according to the sympathetic and renin activity into two contrasting forms: (1) borderline beta-hyperadrenergic renin hyperresponsive and (2) stable beta-hypoadrenergic renin hyporesponsive EH. These two forms probably represent two expreme poles in the spectrum of EH in which sympathetic and renin hyper- or hyporeactivity cannot be accounted for by catecholamine determinations solely. beta-Adrenergic responsiveness monitored by plasma cyclic AMP determinations revealed plasma cyclic AMP, renin and circulatory hyperresponsiveness to isoproterenol in borderline hyperadrenergic EH while the opposite, cyclic AMP and renin hyporesponsiveness to insulin-induced hypoglycemia have been described in low renin stable EH. The kidney is in the center of the adrenergic abnormality in the two forms of EH with the borderline one excreting into the urine catecholamines not accounted for by their glomerular filtration. Catecholamines solely, however, do not account for the differences in both forms of EH which can probably be attributed to their different beta-adrenergic responsiveness.

Adrenergic beta-Antagonists↗

Effects of angiotensin II on steroid metabolism and hepatic blood flow in man.

Metabolic clearance rates (MCR) of aldosterone, cortisol, 11-deoxycorticosterone (DOC), corticosterone, and progesterone were simultaneously measured by constant infusion in eight control subjects before and during angiotensin II infusion in subpressor (3 ng/min per kg) and pressor (22 ng/min per kg) doses. Plasma levels of aldosterone and cortisol, the heat-labile protein-bound fraction of aldosterone, and hepatic blood flow (HBF) (as estimated by the fractional clearance of indocyanine green) were determined concomitantly. Angiotensin II in a subpressor dose produced a significant decrease of the MCR of aldosterone (by 23%), cortisol (by 16%), DOC (by 26%), corticosterone (by 14%) and progesterone (by 33%). The pressor dose further decreased the respective MCR by 37%, 21%, 40%, 28%, and 42% of the baseline value. Plasma aldosterone levels rose by 317% with subpressor and by 434% with pressor doses. HBF decreased by 18% with subpressor and by 33% with pressor doses of angiotensin II. Furthermore, there were significant negative correlations between the MCR of each steroid and the respective values of the fractional clearance of indocyanine green. We conclude that angiotensin II, by its vasoconstrictive action on the splanchnic vascular bed, decreases the MCR of aldosterone, cortisol, DOC, corticosterone, and progesterone. This decrease has to be taken into account when considering the stimulatory effect of angiotensin II on various plasma steroid concentrations.

Adrenal Cortex Hormones↗

Catecholamine excretion in "idiopathic" edema: decreased dopamine excretion, a pathogenic factor?

In 16 women with idiopathic edema, urinary dopamine excretion was decreased when compared to control women (146 +/- 13 SE ng/ml/m2 vs. 212 +/- 32, P less than 0.05 in the supine position and 140 +/- 9 vs. 199 +/- 20, P less than 0.005 combined values of supine and recumbent positions) and was also lower when pooled values for urinary dopamine excretions both before and after furosemide were compared in idiopathic edema patients and in control subjects (270 +/- 30 ng/ml vs. 480 +/- 70, P less than 0.05). These patients have lower basal sodium excretions, decreased tubular rejection fractions of sodium in the upright position and lower urinary sodium excretions following furosemide administration. The urinary sodium and dopamine excretions before and following furosemide are positively correlated in control (P less than 0.05), idiopathic edema patients (P less than 0.02) and in both groups combined (P less than 0.005). Idiopathic edema patients have normal urinary noradrenaline and adrenaline excretions but, as previously observed, elevated: 1) plasma renin activity while either recumbent or upright, and 2) plasma aldosterone concentrations while upright. These results suggest that a decrease in urinary dopamine, a catecholamine recently recognized to have natriuretic action, possibly reflects a suppression of the renal dopaminergic system and may contribute to the excessive sodium retention in idiopathic edema either directly or indirectly through the renin-aldosterone system.

Adult↗