Maternal, fetal and neonatal effects of chronic propranolol administration in the rat.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to S Spector.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Monoamine oxidase (MAO) activity was assayed both in central and peripheral blood vessels of spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKR). The activity of MAO in the brain and peripheral vasculature was essentially the same in both SHR and WKR. It can therefore be concluded that central and peripheral vascular MAO activity is not altered in the genetically hypertensive animals.
Explore the source record for details and available documents.
A nonpeptide morphine-like compound (MLC) which cross reacts with morphine-specific antibodies has been localized with the use of immunocytochemistry. This morphine-like compound is found in neuronal perikarya or processes (or both) in nuclei related to vestibular, cerebellar, and raphe systems.
Monocyte cellular function in 15 asthmatics on alternate-day steroid therapy (mean dose of prednisone, 45.4 +/- 17.45 mg qod) was studied at 8 A.M. and noon after receiving an 8 A.M. steroid dose and at 8 A.M. the following day, and was contrasted to function in 16 healthy controls. Monocyte chemotaxis, bacterial killing and phagocytosis, and oil phagocytosis were not significantly altered by the steroid dose. On the other hand, all the patients experienced monocytopenia, lymphopenia, and neutrophilia 4 hr following the administration of steroid. The lack of functional impairment on this clinically relevant steroid regimen is consistent with the lack of serious infections seen in patients on such regimens. This study re-enforces the need to differentiate the effect of even small doses of steroid on circulating cell populations from direct effects on cell function which occur only with very high or frequent steroid dose regimens.
Explore the source record for details and available documents.
Collagen synthesis was increased in aortas, mesenteric arteries, cerebral microvessels, pial artery, basilar artery and decreased in the heart of rats made hypertensive with deoxycorticosterone acetate-salt or the spontaneously hypertensive animal. The markers of collagen biosynthesis that were elevated were prolyl hydroxylase, prolyl hydroxylase-related antigen, total collagen content and the incorporation of labelled proline into total protein and into collagen. The antihypertensive drugs reserpine and chlorthiazide could both prevent the increase or reduce the increase in collagen synthesis.
The rat cerebral microvessels were isolated and assayed both for monoamine oxidase (MAO) and catechol-o-methyltransferase (COMT) activities. Cerebral microvessels and brain filtrate were found to contain both forms (A & B) of MAO. On a per mg protein basis, the cerebral microvessels contained the greatest activity of MAO and COMT than that of brain filtrate and mesenteric artery. Chemical sympathectomy using 6-hydroxydopamine neither decreased total MAO activity, nor the A form of the enzyme, nor did it have any effect on COMT activity in the brain microvessels. These results suggest that COMT and both forms of MAO in the rat brain microvessels are extraneuronal in origin.
The disposition of the potent antihypertensive drug clonidine has been poorly understood through the lack of a convenient and sensitive assay. A radioimmunoassay for clonidine has been developed and is capable of detecting as little as 10 pg of clonidine. 2,6-Dichlorophenyl-guanidine, a known metabolite of clonidine, did not cross-react with the antiserum whereas another metabolite, 4-hydroxyclonidine, was as potent as clonidine in displacing labeled clonidine from the antibody. However, a simple solvent extraction step before the radioimmunoassay selectively extracted clonidine from a mixture of clonidine and 4-hydroxyclonidine in alkaline plasma and this procedure permitted a specific assay for clonidine. The plasma levels of clonidine in rats after the administration of a hypotensive dose (100 microgram/kg i.v.) were determined by radioimmunoassay and these data indicated that the disposition of clonidine conforms to an open two-compartment, pharmacokinetic model. Clonidine rapidly accumulated in the brain as shown by the attainment of peak concentrations within 2 min of i.v. injection.
Intraventricular administration of norepinephrine (NE) into pentobarbital anesthetized rats elicits a pressor or a depressor effect depending on the dose injected: after a low dose, a depressor response is seen while after a high dose, a pressor response is observed. In the animal pretreated intraventricularly with clorgyline or pyrogallol, the hypotensive effect of a low dose of NE was reversed to a hypertensive effect, while the hypertensive effect of a high dose of NE was markedly potentiated. This result suggests that brain monoamine oxidase and catechol-o-methyltransferase can metabolize centrally released NE before it leaks into the peripheral circulation.
In two models of hypertension in rats, it was shown that collagen synthesis and deposition are increased in arteries where blood pressure is elevated. By contrast, there were no alterations in any of the markers of collagen synthesis in veins, where blood pressure was only slightly elevated. It would appear that the stimulus for vascular collagen synthesis is provided by a direct effect of the increased pressure on the arterial cells rather than by a humoral factor released into the general circulation.
The present study examined the effects of antihypertensive drugs (hydrochlorothiazide and guanethidine) on blood pressure and tyrosine hydroxylase (TH) activity in the spontaneously hypertensive rat (SHR). Hydrochlorothiazide (50 mg/kg X 4 days) lowered blood pressure in the SHR to a degree equivalent to that produced by reserpine (0.3 mg/kg X 3 days). However, while reserpine increased vascular and adrenal TH activity, hydrochlorothiazide had no effect. Guanethidine (30 mg/kg X 2 days) reduced blood pressure in the SHR and also depleted cardiac, vascular and adrenal gland catecholamines; However, guanethidine administration did not increase TH activity in the mesenteric vasculature or adrenal glands. These studies indicate that at equieffective blood pressure lowering doses, different antihypertensive drugs have different effects on TH activity in the SHR. Neither blood pressure reduction nor catecholamine depletion in peripheral tissues are sufficient prerequisties for increasing TH activity. The data support the suggestion, however, that amine depletion in the central nervous system or ganglia may be an important factor in the regulation of TH.
Mice were placed on an immunization schedule known to result in the production of antibodies directed against a variety of barbiturates (antibody binding capacity = 2.71 pmole 3H-phenobarbital bound/ml undiluted serum). The pharmacologic response to barbiturate in these actively immunized mice and suitably treated controls was investigates using rotarod apparatus for monitoring CNS depression. It was found that the response to pentobarbital in actively immunized mice was decreased, as reflected by an increase in the time the mice remained on the rotarod and a shift of the dose--response curve to the right. The decreased pharmacologic response to pentobarbital was not the result of changes in levels of the hepatic drug metabolism components. Furthermore, the alteration of pharmacologic response in actively immunized mice was selective for barbiturate and did not modify the ataxia produced by administration of another depressant agent, ethanol.
Norepinephrine (NE), dopamine (DA), tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) levels were measured in human brain tissue obtained at autopsy from a series of 39 patients dying of various medical and accidental causes. The nine following brain areas were studied: globus pallidus, thalamus, hypothalamus, hippocampus, substantia nigra, floor of the fourth ventricle, orbital cortex, caudate nucleus, and mammillary bodies. Enzyme activity correlated positively with age in all brain areas for MAO (with both benzylamine and tryptamine substrates) but no consistent pattern of correlation was found for COMT and TH. Mean MAO activity was significantly higher in women than men. There is increased brain MAO activity during late childhood and adolescence. These data are consistent with previous evidence suggesting that age and sex are important determinants of amine metabolism in the human central nervous system.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The effect of troleandomycin, a macrolide antibiotic, on theophylline elimination was examined in eight patients with chronic asthma. Clearance from serum was reduced by 50 +/- 6% (mean +/- SD) during administration of 250 mg troleandomycin four times daily. Reduction of clearance persisted to a lesser degree in one of these patients examined while receiving 250 mg troleandomycin daily. An increase in serum theophylline concentration can thus result from initiating troleandomycin in asthmatic patients receiving continuous treatment with theophylline. This may be at least a partial explanation for the apparent benefit of troleandomycin in chronic asthma and also suggests that possibility of inducing theophylline toxicity, including seizures, as was observed in one of the patients in this study.