Atropine lowers blood pressure in normotensive rats through blockade of alpha-adrenergic receptors.
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Biomedical subjects
Publications and source records attributed to S Spector.
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The hypotensive effect of atropine sulfate was evaluated in conscious, unanesthetized hypertensive rats (spontaneously hypertensive rats and Sprague-Dawley rats made hypertensive by s.c. implantation of deoxycorticosterone acetate, tablets) and their respective normotensive controls. In all animals, atropine (5-50 mg/kg i.v.) caused an immediate and dose-dependent decrease in blood pressure. However, the hypotensive response was of greater magnitude and of longer duration in the hypertensive rats. Pretreatment of the animals with phentolamine prevented the hypotension by atropine. Plasma concentrations of atropine were determined by radioimmunoassay and were identical in both hypertensive and normotensive rats. Atropine blocked the pressor responses to norepinephrine and shifted the dose-response curve for norepinephrine to the right to a similar extent in spontaneously hypertensive and Wistar-Kyoto rats. Thus, atropine acts as a competitive antagonist of norepinephrine and this action underlies its hypotensive effect. The greater responsiveness of hypertensive rats is not due to a difference in pharmacokinetic handling of atropine nor to a greater degree of blockade of the norepinephrine pressor response in vivo, but may result from the altered sympathetic tone in the hypertensive rats. Atropine may, in addition to its action on alpha adrenergic receptors, affect other systems such as calcium handling. It is speculated that an effect on this system may contribute to the longer duration of response seen in hypertensive rats.
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The pharmacokinetics of d-tubocurarine (dTc) and the urinary excretion of dTc were studied in 18 neurosurgical patients with normal renal function, over a period of 96 hours. The effects of an osmotic diuretic (mannitol) on urinary elimination of dTc were determined. Following a single intravenous dose of d-tubocurarine (dTc, 0.3 mg/kg), serum levels and urinary excretion of the drug were measured. A specific radioimmunoassay was used for the analysis of dTc. Nine of the patients also received mannitol, 1 g/kg, after the injection of dTc for surgical indications. The study showed that only 45 per cent of the injected dose of dTc was excreted in 24 hours. Between 24 and 96 hours, an additional 7 per cent of the drug was excreted in the urine. The administration of mannitol, an osmotic diuretic, did not increase the excretion of dTc. The time-concentration relationship of serum concentration of dTc was analyzed. Using the four-exponential equation (data to 96 hours), the calculated volume of distribution (Vdarea) was 3.4 1/kg. This volume, which is greater than the volume of total body water, suggests that dTc is stored in certain tissues in the body and slowly released over a period of days to weeks.
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Antibody titers to three common strains of influenza virus, including the Swine Flu strain, were determined in 152 patients in an allergy and pediatric allergy practice prior to planned immunization with influenza vaccine. Because allergic patients are considered to be more prone to hypersensitivity reactions than individuals who are non-allergic, it was deemed prudent to screen for patients who might have pre-existing protective levels of antibody to the viruses. A considerable number of the 152 patients were found to have titers of 1:20 or 1:40 to one or more of the three influenza strains, including the Swine Flu strain. The largest percentage of positive antibody levels was found to be to the A-Victoria strain which has recently been most prevalent in the northeastern United States. The lowest numbers of patients with protective antibody levels were for the Swine Flu strain. Nevertheless, the highest titers occurred with patient specimens tested against the Swine Flu strain. Approximately one-quarter of the patients showed significant levels of antibody (1:40 or more) to one or more of the virus antigens and thus were not vaccinated, avoiding the possibility of untoward areactions which habe been observed in some individuals who have been given the vaccine.
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Rabbits were actively immunized using a barbiturate--BGG conjugate as the immunogen. The antiserum obtained from actively immunized rabbits was administered intravenously to mice to accomplish passive immunization. The antibody binding capacity for 3H-phenobarbital was shown to be sustained in passively immunized mice for periods of up to three weeks. Serum levels of 3H-phenobarbital in passively immunized mice and control mice were compared following drug administration and found to be altered in the antibody-containing mice. There was a 4-fold higher amount of 3H-phenobarbital present in the serum of passively immunized mice compared to control animals. The higher barbiturate levels were due to binding of 3H-phenobarbital to globulin fraction of serum in passively immunized mice. Additionally, decreased pentobarbital-induced ataxia was demonstrated in passively immunized mice. The decreased responsiveness was selective for barbiturates in passively immunized mice and did not modify the ataxia produced in these animals by another depressant agent, ethanol.
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Two endogenous ligands for the brain benzodiazepine-binding sites were isolated from bovine brain through gel filtration, paper electrophoresis, and paper chromatography. These ligands were identified as inosine and hypoxanthine, and both had a higher affinity for the brain benzodiazepine-binding sites than for benzodiazepine sites in some peripheral tissues. They did not bind to any other receptors tested, such as the opiate, muscarinic cholinergic, gamma-aminobutyric acid, and beta-adrenergic receptors. Both inosine and hypoxanthine competitively inhibited the binding of [3H]diazepam to the brain binding site.
In a study of infection due to Chlamydia trachomatis in infants, chlamydiae were recovered not only from the conjunctiva and respiratory tract but also from the vagina and rectum. The timing of recovery suggested that the vagina and conjunctivae are exposed to chlamydiae at birth and that pneumonia and gastrointestinal infection occur later. Sampling of the rectum may be a useful procedure for the diagnosis of chlamydial disease in infants.
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The effect of guanethidine on collagen biosynthesis in the aorta and mesenteric artery was investigated in desoxycorticosterone acetate (DOCA)-salt hypertensive rats. Prolyl hydroxylase activity (EC 1.14.11.2; proline, 2-oxoglutarate dioxygenase) and 14C-proline incorporation into collagen, two markers of collagen biosynthesis, were significantly increased in blood vessels of hypertensive rats compared with those of controls. When guanethidine (5 mg/kg, i.p.) was given daily to the hypertensive rats for 4 weeks, the blood pressure was decreased to 150 +/- 7 mm Hg, whereas the blood pressure of the untreated hypertensive rats was 218 +/- 10 mm Hg. Prolyl hydroxylase activity in the aorta and mesenteric artery and 14C-proline incorporation into aortic collagen were significantly reduced concomitant with the decrease in blood pressure. These results suggest that the decrease in vascular collagen biosynthesis in hypertensive rats treated with guanethidine is related to the lowering of their blood pressure.
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