bluuebunny/crossref_metadata_2025 huggingface dataset:
A Difference in Sensitivity to Alpha-Adrenergic Agonists Exhibited by Detrusor and Bladder Neck of Rabbit
Authors: Downie J. W. , Dean D. M. , Carro-Ciampi G. , Awad S. A.
Published: April 2011

In cumulative dose–response studies, strips from bladder neck of rabbit were significantly more sensitive to stimulation with noradrenaline, phenylephrine, and methoxamine than were strips from detrusor. There was no difference between the two regions in sensitivity to isoprenaline or carbachol. From the known characteristics of these agents, it seemed unlikely that metabolic destruction or uptake could account for the different sensitivities seen. Also, neither normetanephrine nor desmethylimipramine could alter significantly the potency of noradrenaline in either area of the bladder. It seems likely that the difference in sensitivity to alpha-adrenoceptor stimulation in the bladder neck and detrusor is due to factors at the receptor level.
Interactions of Respiration and the Bradycardia of Submersion in Harbor Seals
Authors: Tanji D. G. , Weste J. , Dykes R. W.
Published: April 2011

Six harbor seals with percutaneous tracheostomies were artificially ventilated while immersed. Changes in the oxygen content of the inspired gas and in the minute-volume altered the magnitude of the bradycardia observed after the animal had been submerged for 30 s. The average heart rate in five seals changed from 16.7 (S.D. = 4.4) beats per minute during artificial ventilation with N2, to 58.7 (S.D. = 10.4) beats per minute while breathing air, but this cardiac chronotropic effect of oxygen was blocked by addition of 7% CO2 to the inspired gas. Ventilatory minute-volumes above approximately 3 litres/min caused cardiac acceleration in a manner related to ventilation; below this, changes in heart rate were inconsistent. While being artificially ventilated with air, the average heart rate in five seals changed from 16.5 beats per minute to 73.4 beats per minute as ventilation was increased from 0 to > 8 litres/min. These experiments demonstrate that O2, CO2, and ventilatory minute-volume have significant effects upon the heart rate of seals under water and suggest the presence of chemoreceptor-mediated effects on heart rate during submersion.
Roles of the AV Junction in Determining the Ventricular Response to Atrial Fibrillation
Authors: Billette Jacques , Roberge Fernand A. , Nadeau Réginald A.
Published: April 2011

The statistical properties of RR interval sequences during cholinergic atrial fibrillation were studied in anesthetized dogs both in control conditions and after the selective injection of dromotropic agents into the atrioventricular (AV) node artery. It was observed that RR interval histogram configurations depended mainly on the mean heart rate, regardless of whether it was a control or a post-injection sequence. The sequences were found to vary from almost regular at fast rates to highly irregular at slow rates, covering all intermediate possibilities. Since the injections of dromotropic agents into the AV node artery were carried out during sinus rhythm between the episodes of fibrillation, their influences on the AV junction, as reflected both on the length of the PR interval during sinus rhythm and on the RR interval dispersion during fibrillation, could be compared. The dispersion of RR intervals was found to increase as the PR interval duration became longer. In addition, it was observed that the generally random character of the RR interval sequences during fibrillation was not affected by the injection of dromotropic agents into the AV node artery. These results were interpreted as an indication that, for a well-established atrial fibrillation, the degree of ventricular irregularity (dispersion of RR intervals) is related to the conductivity within the AV junction and that the random character of RR interval sequences is related to the atrial fibrillatory activity itself.
Metabolism of [2-14C]Prostaglandin E1 on Passage Through the Pulmonary Circulation
Authors: Dawson Christopher A. , Cozzini Bruce O. , Lonigro Andrew J.
Published: April 2011

A multiple indicator dilution technique was used to study inactivation of [14C] prostaglandin E1 (PGE1) by isolated cat lungs. A bolus containing [2-14C]PGE1, indocyanine green dye and 3HOH was rapidly introduced into the blood entering the pulmonary artery. Sequential samples of the venous effluent were collected and analyzed for 3H, dye, and 14C. The 14C-labelled compounds were separated by thin-layer chromatography, and the quantity of PGE, and its metabolites contained in each sample was determined (radiochromatogram scanning). Recovery of the dye and 3H was complete within the sampling period. However, only 79% of the injected 14C emerged from the lung within this period, 36% as [14C]PGE1, and 43% as two less polar metabolites. The mean transit times (including connecting tubing) for the unmetabolized [14C]PGE1 and the dye were 9.1 and 8.7 s, respectively. The apparent mean transit times for 14C in the metabolites were considerably longer, 12.4 and 14.3 s. The 3HOH mean transit time was 10.7 s. These data are compatible with an extraluminal site for PGE1 metabolism.
Regional Cerebral Blood Flow of the Rat in Acute Carbon Monoxide Intoxication
Authors: MacMillan V.
Published: April 2011

The effect of carbon monoxide (CO) on the regional cerebral blood flow was studied by exposing lightly anesthetized rats for 30 min to 0.5, 1.0, 1.5, and 2.0% CO gas mixtures. Cortical cerebral blood flow (CBF) increases of near 200%, 300%, and 400% control were observed at 0.5, 1.0, and 1.5% CO, respectively; whereas at 2.0% CO a reversal of the CBF increase was observed with values declining to near 300% control. The CBF response of subcortical, cerebellar, and brain stem areas was quantitatively similar to that of cortex, indicating that the CBF changes in CO intoxication are general. The decrease in CBF at 2.0% CO was related to significant decreases in arterial CO2 tension. Comparison of the CBF data to previous metabolic results in CO poisoning suggests that the CBF increases are a principal factor in the maintenance of an intact energy state in CO poisoning.
A Scanning Electron Microscope Study of Human Cerebral Arteries
Authors: Cope David A. , Roach Margot R.
Published: April 2011

Human cerebral arteries were obtained from autopsy, fixed under pressure, cut open, and tacked onto pieces of cork. For one artery the intima was partly teased away, exposing the media, and treated with a silver nitrate process. For another artery the adventitia was exposed. Both arteries were processed through graded ethanols and coated with gold paladium for the scanning electron microscope.The collagen fibers of the adventitia were approximately 5 μm in diameter and consisted of a bundle of microfilaments, each of which had a diameter of 800–1000 Å (1 Å = 10−10 m). The collagen fibers were oriented parallel to the long axis of the artery. The muscle cells of the media had a diameter of 2–5 μm and were arranged circumferentially with a pitch of approximately 20°. The collagen fibers of the media travel perpendicular to the muscle cells, and parallel to the long axis of the artery. The fibrillar components of the elastin in the intima had a diameter of approximately 700–1000 Å and were arranged parallel to the long axis of the artery. It was postulated that the fibrillar part of the elastin was the elastic component of the elastin.
Morphine Excitation in the Cerebral Cortex
Authors: Bioulac B. , Lund J. P. , Puil E.
Published: April 2011

Microiontophoretic administrations of morphine to cholino-excitable neurones in the cerebral cortex of decerebrate cats evoked a weak excitation which became more prominent upon repeated administrations of the alkaloid. This effect was not antagonized by naloxone. Iontophoresis of methylatropine prevented the excitation induced with acetylcholine and morphine, leaving that caused by glutamate relatively unaltered. Similar applications of morphine to neurones which were not excited by test applications of acetylcholine did not result in excitation but elicited mainly a depression of glutamate-evoked firing. It is suggested that the muscarinic effect of morphine in the cortex may be related to the excitation and convulsions, but not the analgesia, which occurs upon systemic administrations of the narcotic.
Concentration and Bioassay of a Natriuretic Factor in Plasma of Volume Expanded Rats
Authors: Pearce J. W. , Veress A. T.
Published: April 2011

Plasma was obtained by an isovolaemic exchange procedure from rats undergoing sustained blood volume expansion (experimental) and from normovolaemic but otherwise similarly prepared rats (control). Four plasma fractions, showing absorption at 280 nm, were separated by G-50 Sephadex gel filtration, freeze dried and reconstituted for assay in hydropaenic rats for natriuretic activity. Only the large protein fraction (molecular weight exceeding 30 000) of experimental plasma produced a significantly greater natriuresis than the corresponding fraction from either control plasma or a fractionated 5.6% albumin solution. The respective averaged peak differences in sodium excretion were 4 and 3.5 μequiv./min per gram kidney weight. This additional natriuretic activity was attributed to a humoral factor, either a protein or a protein-bound moiety, generated by vascular expansion.
The Effect of Norethandrolone on Organic Ion Transport by Rat Renal Cortical Slices
Authors: Watrous William M. , Lacombe Richard , Brodeur Jules
Published: April 2011

Norethandrolone (NE) and other androgenic steroids have been shown to be renotropic in various species and have also been reported to have salutary effects in patients with diminished renal function. Renal cortical slices prepared from rats pretreated with NE showed an increased capability to concentrate p-aminohippuric acid (PAH). Pretreatment with NE failed to stimulate the transport of the organic base tetraethylammonium and the organic acid benzylpenicillin. Stimulation of PAH transport was observed after eight daily subcutaneous injections of NE. No stimulation was observed with shorter pretreatment intervals. When NE was given subcutaneously for 14 days at doses of 2, 6, or 20 mg kg−1 day−1, significant stimulation of PAH transport was seen at all three dose levels but no dose–effect relationship was apparent. Stimulation of PAH transport was seen in female rats as well as castrated and intact males. In addition to its general anabolic properties, NE induces the synthesis of hepatic microsomal drug-metabolizing enzymes. For comparative purposes, therefore, the effect of pregnenolone-16α-carbonitrile (PCN) was also investigated. This agent is a potent inducer of drug metabolism but is neither anabolic nor renotropic. When rats were pretreated with an inducing dose of PCN (75 mg kg−1 day−1 for 3 days), there was no significant stimulation of PAH transport. It would seem, then, that the stimulatory effect of NE on PAH transport is more closely associated with its generalized anabolic effect than with its ability to induce hepatic microsomal enzymes.
The Effect of Cocaine on the Responses of the Differently Innervated Laryngeal and Bronchial Ends of the Guinea Pig Trachea in Vitro to Clinically used Bronchodilators
Authors: Jones Thomas R. , Hamilton John T. , Lefcoe Neville M.
Published: April 2011

Fluorescent histochemical studies indicate that guinea pig tracheal smooth muscle has sparse adrenergic innervation with the greatest nerve density being located at the laryngeal end. In the present study, log dose–response lines were obtained for dl-isoprenaline (ISO), l-adrenaline (ADR), l-noradrenaline (NOR), salbutamol (SALB), and orciprenaline on isolated tracheal chains prepared from both the laryngeal (L) and bronchial (B) ends of the trachea. Responses were obtained in the absence and presence of the Uptake1 blocker, cocaine (0.67 and 6.7 μM) which markedly potentiated responses to NOR and ADR but failed to significantly alter responses to ISO and SALB on L preparations. The degree of potentiation obtained on B preparations was significantly less for NOR and ADR and was not significant for the other agents. In addition, experiments were carried out on tracheal chains which developed their normal tone in the absence of carbachol, and also on preparations obtained from 6-hydroxydopamine treated animals. The present findings, based on selective potentiation of NOR and ADR, support evidence that the degree of adrenergic innervation to the guinea pig trachea is greater at the laryngeal end, and the results obtained with cocaine strengthen the argument that it has a pre-synaptic site of action.
Structure–Activity Relations for the Acceleration of Efflux of Noradrenaline from Adrenergic Nerves in Rabbit Atria by Sympathomimetic Amines
Authors: Paton D. M.
Published: April 2011

Atria from reserpine-pretreated rabbits were exposed to pargyline to inhibit monoamine oxidase (amine oxidase (flavin-containing) EC 1.4.3.4) and subsequently incubated in (−)-[3H]noradrenaline to allow the cytoplasmic accumulation of amine in adrenergic nerves. The structure–activity relations for acceleration of efflux of cytoplasmic amine were examined. The most potent agents studied were (+)- and (−)-amphetamine, β-phenethylamine, phentermine, and mephentermine. Ability to accelerate efflux was reduced by addition of phenolic hydroxyl groups, by phenolic methylation, by β-hydroxylation, and by N-substitution. The structure–activity relations for acceleration of efflux differ notably from those for uptake, inhibition of uptake, or release of noradrenaline from adrenergic nerves, reported in previous studies. The ability and potency of a given phenethylamine derivative to accelerate the efflux of cytoplasmic noradrenaline is probably determined by such factors as the lipid solubility of the amine, the affinity of the amine for the uptake and efflux site(s) for noradrenaline, and competition for any reserpine-resistant intraneuronal binding sites.
Contractile Responses of Canine Isolated Pulmonary Lobar Arteries and Veins to Norepinephrine, Serotonin, and Tyramine
Authors: Joiner Paul D. , Kadowitz Philip J. , Davis Linda B. , Hyman Albert L.
Published: April 2011

Isolated helical strips of canine intrapulmonary lobar arteries and veins (about 4 mm in diameter) undergo dose-related tension development when exposed to increasing concentrations (10−8 – 10−3 M) of norepinephrine (NE), serotonin or 5-hydroxytryptamine (5-HT) and tyramine (Tyr). Venous segments were generally more sensitive while the maximum tension development was greater in the arterial strips, probably owing to their greater thickness. Both strips were more sensitive to 5-HT than NE and only responded to Tyr at high concentrations. Norepinephrine and 5-HT were nearly equally efficacious, whereas Tyr was less so. Responses to the latter were slow to develop, exhibited tachyphylaxis, and were greatly inhibited by phentolamine (10−8 M), an α-adrenergic blocker. Exposure to cocaine (10−5 M) enhanced submaximal NE responses, inhibited Tyr contractions and had no consistent effect on 5-HT responses. Phentolamine (10−8 M) was also found to inhibit NE responses without altering 5-HT effects, whereas methysergide (10−8 M) inhibited 5-HT responses but not NE contractions. Thus, evidence suggests that NE probably acts on α-adrenergic receptors whereas 5-HT probably acts on other receptors. Tyramine may, in part, act directly on α-adrenergic receptors but may also release NE from surviving adrenergic nerve terminals in the preparation. Cocaine inhibits this effect and potentiates responses to lower levels of NE, presumably by blocking NE uptake into nerve terminals although a post-junctional action cannot be excluded.
Effects of Testosterone Metabolites on Serum Gonadotropin Concentrations in Immature Male Rats
Authors: Moger William H.
Published: April 2011

The ability of testosterone, androsterone, 5α-androstane-3α,17β-diol, and 5α-androstane-3β,17β-diol to prevent the castration-induced rise in serum gonadotropin levels was investigated in immature male rats. Rats castrated at 30 days of age were treated once per day by subcutaneous injection of 12.5–100 μg of the steroid per 100 g body weight per day for 3 days, beginning on the day of castration. The animals were sacrificed 24 h after the last injection. Testosterone propionate, androsterone propionate, and 5α-androstane-3α,17β-diol dipropionate were also tested at the approximate molar equivalent of 100 μg of the free alcohol form per 100 g body weight per day.Testosterone propionate and 5α-androstane-3α,17β-diol were the only compounds tested that prevented the castration induced rise in luteinizing hormone (LH) concentrations. Testosterone propionate also inhibited the rise in follicle stimulating hormone (FSH) concentrations whereas 5α-androstane-3α,17β-diol inhibited the rise in FSH in one but not in another experiment. These were the only compounds tested that affected serum FSH concentrations.The lower doses of testosterone tested significantly increased serum LH, but not FSH concentrations compared to castrate control animals. The highest dose tested partially inhibited the rise in serum LH concentrations.Both androsterone and androsterone propionate maintained ventral prostate weights. Although neither compound prevented the castration induced rise in serum LH, two groups receiving androsterone had serum LH concentrations significantly lower than the castrate control group.5α-Androstane-3β,17β-diol and 5α-androstane-3α,17β-diol dipropionate failed to maintain ventral prostate weights or prevent the rise in serum gonadotropin levels.These results indicate that 5α-androstane-3α,17β-diol is capable of preventing the castration induced rise in serum LH concentrations in the immature male rat and thus may participate in the regulation of LH secretion in these animals.
Effects Produced by Local Applications of Harmaline in the Inferior Olive
Authors: Montigny C. De , Lamarre Y.
Published: April 2011

Local microinjections of harmaline evoked sustained rhythmic activity in the inferior olive of decerebrate cats. Harmaline appears to exert its action within restricted areas of the inferior olivary complex: the caudal halves of the dorsal and medial accessory nuclei. Since the highly synchronized activity generated by harmaline can be attributed to extensive electrotonic coupling between olivary neurones, it is postulated that such a coupling mechanism is weaker if not absent in the principal olive and in the rostral parts of the accessory nuclei.
Correlation Between Extracellular Focal Potentials and K+ Potentials Evoked by Primary Afferent Activity
Authors: Krnjević K. , Morris M. E.
Published: April 2011

There is a clear, positive correlation in amplitude between changes in potassium potentials (ΔEK) and focal potentials (ΔV) evoked by tetanic stimulation of afferent nerves in the cuneate nucleus and dorsal horn of cats under Dial anaesthesia or after decerebration. Data obtained with stimulations at various frequencies and intensities, or recording at different positions give a relatively constant slope of ΔV/ΔEK (varying between 0.2 and 0.6 in different experiments). These observations are fully consistent with the possibility that ΔV mainly reflects changes in extracellular potassium concentration caused by the release of K+ from active terminals. Differences in time course of ΔEK and ΔV evoked by single stimuli are a steep function of distance and therefore can be ascribed to the slowness of diffusion, without excluding the possibility of an early additional depolarizing effect by another mechanism.
Effect of Ouabain on the Innervated and Noninnervated Embryonic Chick Heart
Authors: Lelorier J. , Minejima N. , Shideman F. E.
Published: April 2011

Attempts to assess the importance of the role played by endogenous catecholamines in the positive inotropic response to ouabain have produced contradictory results. The sympathetic nervous system is not present in the 4-day-old chicken embryo heart but is fully developed after 7 days of embryonic life. This was confirmed by the fact 4-day-old hearts do not respond to tyramine and cocaine while the usual positive inotropic and chronotropic responses were observed when these drugs were administered to 7-day-old hearts. In spite of this difference the positive inotropic response to ouabain was virtually identical at these two stages of development.
Interaction of Amphotericin B and Nystatin with Phospholipid Bilayer Membranes: Effect of Cholesterol
Authors: Singer Michael A.
Published: April 2011

Sodium-22 efflux was measured in multilamellar liposomes, exposed to one of the two polyene antibiotics amphotericin B or nystatin. Polyene mediated 22Na transport progressively rises with membrane sterol concentrations up to about 20 mol %, but falls with higher cholesterol concentrations. The polyene induced 22Na movement in cholesterol rich liposomes could be 'restored' by the addition of either dibucaine or propranolol (two local anesthetics) to the aqueous solution. These observations are interpreted in terms of the model of De Kruijff and Demel (Biochim. Biophys. Acta, 339, 57–70, 1974). In this model, nystatin and amphotericin B first complex with cholesterol and then these complexes aggregate to form transmembrane channels. It is here proposed that the aggregation of these complexes is inhibited by a high cholesterol content (decreased membrane fluidity) but that the two local anesthetics, by disrupting phospholipid–sterol interactions (increased membrane fluidity), can 'restore' this process of aggregation.
The Action of the Ionophores, X-537A and A-23187, on Smooth Muscle
Authors: Swamy V. C. , Ticku M. , Triggle C. R. , Triggle D. J.
Published: April 2011

The cation ionophore X-537A in the concentration range of 10−6 to 3 × 10−5 M produced contractions in the rat and guinea-pig vas deferens. No contractile effect was produced in either of the vasa deferentia preparations by the ionophore A-23187 in the concentration range of 10−7 to 5 × 10−5 M. In contrast, X-537A had no contractile effect on the guinea-pig ileal longitudinal smooth muscle while A-23187 produced a dose and [Ca2+] dependent contraction.The contractile effect of X-537A in the vasa deferentia preparations is abolished by phenoxybenzamine or prior reserpine treatment and is therefore attributed to the release of norepinephrine. The effect of A-23187 in the intestinal smooth muscle is attributed to a direct Ca2+ transporting action since its contractile effect is unaffected by histamine, acetylcholine, or 5-hydroxytryptamine antagonists.
Radioimmunoassay Studies of Intestinal Calcium-binding Protein in the Pig. I. Identification of Intestinal Calcium-binding Protein in Blood and Response to a Low Calcium Diet
Authors: Arnold B. M. , Kuttner M. , Swaminathan R. , Care A. D. , Hitchman A. J. W. , Harrison J. E. , Murray T. M.
Published: April 2011

We have developed a radioimmunoassay for porcine intestinal calcium-binding protein (CaBP) and have used it to detect CaBP in pig plasma. Plasma CaBP is identical to intestinal CaBP on the basis of immunological activity, molecular size, and molecular charge properties. The plasma CaBP concentration was greater in the portal blood than in mixed venous blood, suggesting that blood CaBP originates in the gut. Two of four 15-week-old littermate pigs were placed on a low calcium diet (0.15% calcium, 0.65% phosphorus) and two on a control diet (0.65% calcium, 0.65% phosphorus). After 2 weeks, the entire small intestine was removed and divided into nine 1.8-m segments. CaBP was assayed in both plasma and intestinal mucosa. When the two pigs on a low calcium diet were compared with two control pigs, there was a general increase in immunoreactive CaBP in both plasma and intestinal mucosa. However, there was no increment in immunoreactive CaBP in the first 1.8-m segment of small intestine. Seventy-one percent of the increment in CaBP occurred distal to the first two segments. The largest fractional low calcium diet effect occurred in the ileum. The mean CaBP concentration for the total small intestine increased by a factor of 1.9. The plasma CaBP concentration increased by a factor of 2.6. In these pigs, plasma CaBP was a more reliable indicator of change in CaBP status than was the measurement in the proximal gut segment which contained the duodenum. The assay of CaBP in blood is convenient and may obviate the sampling errors inherent in intestinal biopsy.
Increase in Catecholamine Content of the Rat Adrenals After Pretreatment with Diazepam
Authors: Gascon A. L. , Lelorier J.
Published: April 2011

The effect of subacute pretreatment with diazepam was studied on the catecholamine content of the heart and adrenals of the rat. The results show that at all doses studied, subacute treatment with diazepam increases the catecholamine content of the adrenal glands and there is no change in the noradrenaline content of the heart and brain.
Characterization of angiotensin receptors in rabbit isolated atria
Authors: Rioux F. , Park W. K. , Regoli D.
Published: April 2011

Rabbit isolated left atria have been used to study the inotropic action of angiotensin II (ATII). The peptide is active at doses ranging from 1.0 × 10−9 to 2.8 × 10−6 M and its inotropic effect is not modified by sotalol, phentolamine, burimamide, and indomethacin. We therefore propose that this effect results from the stimulation of receptors specific for ATIIDose–response curves of ATII obtained in presence of increasing concentrations of 8-Gly-ATII are gradually displaced to the right, but high doses of the antagonist depressed the maximum contractions caused by ATII.pA2 value for 8-Gly-ATII in this preparation is similar to those observed in vascular and intestinal smooth muscles. Order of potency of analogues of ATII (2-, 3- and 5-Ala-ATII), acting as full agonists, but with reduced affinity, is similar to that found in rabbit aorta strips. It is therefore proposed that receptors for ATII in rabbit isolated left atria are pharmacologically similar to those present in vascular smooth muscles.Positive inotropic effects of angiotensin I, undecapeptide (1-11), dodecapeptide (1-12) and tetradecapeptide (1-14) renin substrate are antagonized by 8-Gly-ATII in a similar way as the effect of ATIIThis suggests that the action of these peptides is mainly due to stimulation of receptors for ATII. The contribution of myocardial converting enzyme to the action of these peptides is discussed.
Critical opening pressure and reactivity of tail vessels in conscious hypertensive rats
Authors: Darke A. C. , Nair P. G. , Gaskell P.
Published: April 2011

The possible role of increased vascular reactivity in the mechanism of experimental hypertension was studied by measurements of the critical opening pressure (COP) of tail vessels in conscious rats. In hypertension induced by administration of desoxycorticosterone acetate (DOCA) and replacement of the drinking water by 1% NaCl solution (DOCA–NaCl hypertension), and in one-kidney Goldblatt renovascular hypertension, the raised level of blood pressure was associated with an increased COP of the tail vessels when measured both before and after ganglionic blockade. In rats treated with either DOCA alone or 1% NaCl alone there was no significant increase in systolic blood pressure (SBP) or COP relative to the corresponding controls. In all four experimental series intravenous infusion of angiotensin or norepinephrine in conscious ganglion-blocked rats produced dose-dependent increases in SBP and COP. In DOCA–NaCl hypertensive rats but not in renovascular hypertensives, nor in rats treated with DOCA alone or 1% NaCl alone, the increase in COP for a given increment in dose of angiotensin or norepinephrine was significantly greater than in the control rats. It is concluded that in DOCA–NaCl hypertension there is a true increase in the reactivity of the smooth muscle of the resistance vessels to angiotensin and norepinephrine. In renovascular hypertension this is not the case and other factors must therefore be involved in causing the increased blood pressure and COP.
Vascular actions of furosemide and bumetanide on the rat superior mesenteric vascular bed: interactions with prolactin and prostaglandins
Authors: Mtabaji J. P. , Manku M. S. , Horrobin D. F.
Published: April 2011

The mesenteric vascular bed of the rat was used to investigate the effects of furosemide, bumetanide, prolactin, aspirin, indomethacin and prostaglandin E2 on the pressor response to norepinephrine. Furosemide, bumetanide and indomethacin could all inhibit the responses to norepinephrine: in each case responsiveness was restored by the addition of prostaglandin E2 to the perfusate. Bumetanide and furosemide both failed to inhibit responsiveness in the presence of an adequate amount (50 pg/ml) of prostaglandin E2. As has been shown previously, ovine prolactin in a concentration of 50 ng/ml enhanced pressor responses to norepinephrine while 500 ng/ml, after an initial potentiation, inhibited responsiveness. Aspirin, furosemide and bumetanide all reversed both the potentiation produced by the lower prolactin concentration and the inhibition produced by the higher one. When taken in conjunction with other evidence these results suggest that the diuretics exert their vascular effects by inhibiting prostaglandin synthesis whereas prolactin acts by stimulating such synthesis.
Effect of [Sar1, Ala8]-angiotensin II and hypophysectomy on the intestinal resistance vessels and blood pressure following furosemide-induced volume depletion
Authors: McNeill J. Robert , Wilcox William C. , Regnault Raoul
Published: April 2011

Intravenous administration of furosemide (2 mg/kg) caused intestinal vasoconstriction in various groups of pentobarbital-anesthetized cats. [Sar1, Ala8]-angiotensin II, a specific competitive antagonist of angiotensin II, was infused 60 min after administration of furosemide, a time when the intestinal vasoconstrictor response to the diuretic was maximal or near maximal. In hypophysectomized animals, infusion of the antagonist abolished the intestinal vasoconstriction and caused a significant fall in arterial pressure even when the intestinal nerves and adrenal glands remained intact. In contrast, the antagonist had little effect when the pituitary gland remained intact. The results suggest that endogenous angiotensin and vasopressin are overlapping mechanisms which constrict the intestinal resistance vessels and support arterial pressure following furosemide-induced volume depletion. In the absence of one control system, the other compensates to maintain the responses.
Duration of analgesia in mice after heroin by two testing methods
Authors: Brands Bruna , Hirst M. , Gowdey C. W.
Published: April 2011

The analgesic action in mice of single injections of heroin hydrochloride ranging from 0.3–240 mg/kg was measured by the tail-clip and by the hot-plate methods. The duration of analgesia increased as the dose of heroin increased. By the tail-clip technique, the mean effective dose (ED50.) (and standard error of estimate) at 30 min was calculated as 1.0 (±3.42) mg/kg while at 180min it was 27.5 (±3.05) By the hot-plate technique the ED50 at 30min was 4.9 (±3.13) mg/kg and at 180 min it was 173.8 (±5.38) mg/kg. The hot-plate method, though less sensitive than the tail-clip method, yields a regression line derived from ED50 values at various testing times of the same slope; thus the two methods give comparable results for changes in analgesia with time. The rate of change of the median analgesic dose of heroin HCl in mice was calculated to be 2% per minute. In similar mice the acute mean lethal dose for single, subcutaneous injections of heroin HCl was calculated to be 190.5 ± 3.01 mg/kg (95% confidence limits).
Lack of a significant protective effect of augmented circulating glucose on the ischemic myocardium
Authors: Spath Jr. James A. , Ogletree Martin L. , Lefer Allan M.
Published: April 2011

Infusion of glucose alone or glucose with insulin in cats subjected to acute myocardial ischemia did not alter the hemodynamic response of the cats to coronary artery ligation. Furthermore, determination of myocardial creatine phosphokinase (CPK) (ATP:creatine N-phosphotransferase, EC 2.7.3.2) activities failed to reveal a protective effect of glucose and insulin upon the status of the developing infarct in the ischemic myocardium. However, glucose and insulin apparently promote clearance of CPK from the plasma and inhibit proteolysis during the early phase of myocardial ischemia. These actions may be of value in generalized adaptive response of the animal to the stress of ischemia, but does not per se appear to diminish the spread of the ischemic damage within the heart nor to limit the extension of the evolving infarct.
Tonin activity in rat saliva: effect of sympathomimetic and parasympathomimetic drugs
Authors: Garcia R. , Boucher R. , Genest J.
Published: April 2011

The effects of carbachol, propranolol and isoproterenol on tonin concentration in rat saliva have been investigated. The results suggest that the activity of this enzyme in rat saliva is dependent on activity of β-adrenergic receptors.
Effect of structural analogs of butaclamol (a new antipsychotic drug) on striatal homovanillic acid and adenyl cyclase of olfactory tubercle in rats
Authors: Pugsley T. A. , Merker J. , Lippmann W.
Published: April 2011

The 3-isopropyl (I), 3-cyclohexyl (II) and 3-phenyl (III) analogs of the new antipsychotic drug butaclamol, which contains a 3-tertiary butyl group, and their respective (+)-enantiomers, but not (−)-enantiomers, caused a dose-related elevation of rat striatal homovanillic acid concentration, indicative of an increased dopamine (DA) turnover; droperidol also exhibited this activity. The order of activity of the (+)-enantiomers was (butaclamol) ≈ II > I > III. A decrease in striatal DA was observed with (+)-I and (+)-III at the highest dose used, but not at one-half the dose. Each analog antagonized the DA-induced increase in adenyl cyclase (EC 4.6.1.1) activity of olfactory tubercle homogenates, the order of activity of the racemates (except for II) and (+)-enantiomers being (butaclamol) ≈ I> III > II. The (+)-enantiomers of butaclamol and analogs were two to four times more potent than their respective racemates, with (+)-butaclamol and (+)-I displaying activity generally equivalent to fluphenazine. The respective (−)-enantiomers were ineffective indicating a stereochemical specificity for DA-receptor blockade. Such analogs presented should be of value in elucidating dopaminergic mechanisms.
Catalepsy induced by morphine or haloperidol: effects of apomorphine and anticholinergic drugs
Authors: Ezrin-Waters C. , Muller P. , Seeman P.
Published: April 2011

To investigate the extent of cholinergic involvement in opiate-induced catalepsy, the effects of three anticholinergic drugs were studied on morphine-induced catalepsy. Haloperidol-induced catalepsy was also examined. Maximum catalepsy in rats was obtained with 30 mg/kg morphine or 3 mg/kg haloperidol. The anticholinergic drugs atropine, benztropine, and scopolamine were unable to antagonize morphine-induced catalepsy, yet readily antagonized haloperidol-induced catalepsy. Low doses of apomorphine (7.5 mg/kg), on the other hand, readily antagonized morphine catalepsy, but 13-fold higher doses of apomorphine were needed to block haloperidol-induced catalepsy. The results are compatible with the idea that catalepsy can be mediated via the striatum or the amygdala; morphine–dopamine antagonism may occur in the amygdala, whereas morphine–dopamine–cholinergic interactions occur in the striatum.
Toxicity testing in vitro. I. The effects of Δ9-tetrahydrocannabinol and aflatoxin B1 on the growth of cultured human fibroblasts
Authors: Cooper James T. , Goldstein Samuel
Published: April 2011

The acute toxicity of Δ9-tetrahydrocannabinol (Δ9-THC) and aflatoxin B1 to two strains of cultured human fibroblasts has been studied. Δ9-THC had no effect on cell plating efficiency or on the growth of mass cultures at doses of 1 μg/ml (3.18 μM) or less; at 10 μg/ml plating efficiency was reduced by approximately half and at 20 μg/ml colony formation was zero. Aflatoxin B1 reduced plating efficiency at dose levels of 0.1 μg/ml (0.32 μM) and above; in mass cultures it retarded growth at 1 μg/ml and produced complete inhibition at 5 μg/ml. The potential usefulness of cultured human fibroblasts in toxicity testing is discussed and the importance of using normal diploid cells rather than aneuploid permanent lines is emphasized. The limitations of cell cultures in assessing toxicity, and possible solutions to these are considered.
The effect of calcium on cardiac phosphorylase activation, contractile force and cyclic AMP in euthyroid and hyperthyroid rat hearts
Authors: Hartley Elizabeth J. , McNeill John H.
Published: April 2011

Calcium chloride injected into isolated perfused rat hearts produced a positive inotropic effect and increased the levels of phosphorylase a (EC 2.4.1.1). The increase in enzyme activity lagged behind the inotropic effect. Pretreatment of animals with thyroid hormone enhanced the ability of noradrenaline to activate phosphorylase but did not affect the inotropic or phosphorylase activating effect of calcium. Thyroid hormone pretreatment did enhance the chronotropic effect of calcium. Calcium did not affect the cardiac levels of cyclic AMP. It is concluded that calcium can activate phosphorylase by a mechanism other than cyclic AMP and that the enhancement of adrenergic amine-induced phosphorylase activation by thyroid hormone is not a calcium mediated event.
The effects of oral diazepam pretreatment on the biliary excretion of sulfobromophthalein in rats
Authors: Hanasono George K. , Repentigny Louis De , Priestly Brian G. , Plaa Gabriel L.
Published: April 2011

Studies were performed with rats to examine the effects of single, as well as repetitive oral diazepam (DZP) pretreatment on biliary sulfobromophthalein (BSP) excretion rates and on bile flow parameters. One-hour pretreatment of male rats with 150 mg/kg of DZP resulted in about a one-third reduction in the peak biliary excretion rate of BSP (60 mg/kg, iv) and this was associated with a decrease in relative proportions of conjugated to unconjugated BSP in bile. The biliary excretion of preconjugated BSP was unaffected. BSP hepatic uptake and storage were apparently unaffected. In vitro DZP markedly inhibited BSP conjugating activity.In contrast to the above results, when BSP excretion was examined 1 h after the last of five daily oral doses of DZP (150 mg kg−1 day−1), no change in the peak elimination rate of this dye was evident. However, bile flow rates were higher in DZP-treated rats than in controls.When rats were examined 24 h after the last of live daily oral doses of DZP (150 mg/kg), the choleretic response persisted. Further studies showed that the repetitive DZP pretreatment enhanced the bile salt-independent mechanisms of bile formation.
Interaction of propranolol and phentolamine with ethanol in the rat
Authors: Frankel D. , Kalant H. , Khanna J. M. , LeBlanc A. E.
Published: April 2011

The possible role of the adrenergic nervous system in the intoxicant effects of ethanol was examined in studies of the interaction of propranolol and phentolamine with ethanol. Propranolol tended to increase the effect of lower doses of ethanol in a dose-dependent manner. However, the effect of higher doses of ethanol (over 2.0 g/kg) tended to be diminished by low doses of propranolol, whereas higher doses of propranolol were ineffective or actually increased the ethanol effect. Phentolamine tended to decrease the effect of the lower ethanol doses. These findings are inconsistent with any simple adrenergic mechanism in the mediation of the intoxicant effect of ethanol.
Influence of infused prolactin on hormone binding to tissue slices
Authors: Holdaway I. M. , Deegan M. , Friesen H. G.
Published: April 2011

The influence of circulating prolactin on the binding of labeled hormone to tissue slices in vitro was investigated in rats bearing dimethylbenzanthracene-induced mammary tumors. Prolactin was infused into four animals over four 30-min periods to give serum levels ranging from 20 to 2000 ng/ml. Serial biopsies of liver and tumor were taken during infusion, and binding of labeled prolactin and insulin measured in tissue slices. Whereas insulin binding remained constant, prolactin binding was significantly depressed in both tissues when samples were obtained at serum prolactin levels greater than 300 ng/ml. This decrease was due to diminished numbers of available binding sites rather than a change in binding-site affinity for prolactin. These data indicate that under the conditions of this experiment, endogenous circulating prolactin may interfere with in vitro measurements of hormone uptake when serum levels exceed 300 ng/ml.
Myocardial lesions in rats fed rapeseed oil. I. Influence of strain of rats
Authors: Hulan H. W. , Kramer J. K. G. , Corner A. H.
Published: April 2011

The influence of strain of rat on the development of myocardial lesions was investigated in an experiment which included two factors: strain (Wistar, Sherman, Chester Beatty (Hooded), and Sprague–Dawley from two sources designated Sprague–Dawley A, Sprague–Dawley C) and diet (5% corn oil, 20% corn oil, and 20% Brassica napus var. Zephyr rapeseed oil). Groups of 30 rats, housed 2 per cage, from each of three different strains of rats and groups of 10 rats, housed 2 per cage, from one strain of rats (Hooded) were fed semisynthetic diets containing the test oils for 16 weeks on an ad libitum basis. Rats of the Hooded strain consumed considerably less feed and grew at a significantly (P < 0.01) slower rate than did rats of the Sprague–Dawley C strain, which in turn ate less and grew significantly (P < 0.01) slower than rats of the other three strains. No marked differences were observed in the fatty acid composition of total cardiac lipids among strains. Rats from all strains except Hooded fed the diet containing 20% Zephyr RSO had a significantly (P < 0.001) higher incidence of myocardial lesions than rats fed the 20% corn oil diet which in turn had a significantly (P < 0.001) higher incidence than rats fed 5% corn oil. Similarly, significantly (P < 0.05) more Sprague–Dawley C rats had myocardial lesions than Sprague–Dawley A rats regardless of diet. None of the Hooded rats fed the diet containing 20% Zephyr RSO developed myocardial lesions whereas all other strains fed this diet developed a high incidence of myocardial lesions.
Actions of prednisolone acetate, pregnenolone-16α-carbonitrile, and triamcinolone upon drug resistance and metabolism: a comparative study
Authors: Kourounakis P. , Selye H.
Published: April 2011

In female rats, pretreatment with prednisolone acetate diminished the duration of zoxazolamine-induced paralysis as well as its plasma concentrations and increased significantly the in vitro metabolism of zoxazolamine and ethylmorphine. These actions of prednisolone were compared with those of equimolar amounts of pregnenolone-16α-carbonitrile (PCN) (a known microsomal enzyme inducer) and of triamcinolone (an agent that reduces the sensitivity of the body to drugs although not via microsomal enzyme induction). Prednisolone proved to be a strong drug-metabolizing enzyme inducer but it was less potent than PCN.
Depression by magnesium ion of neuronal excitability in tissue cultures of central nervous system
Authors: Wojtowicz J. M. , Marshall K. C. , Hendelman W. J.
Published: April 2011

Magesium ion (Mg2+) in concentrations of 5–10 mM has been used to block synaptic transmission in in vitro preparations of central nervous system tissue. We have used explants of mouse cerebellum grown in culture to test whether significant levels of direct depression of neuronal membrane excitability could occur in such experiments. Using thresholds for antidromic activation and iontophoretically applied glutamate as tests of excitability, potent depressions of membrane excitability were found using 5–10 mM Mg2+. The additive depressant effects of increased Ca2+ concentrations provided further evidence that the effects were largely on membrane excitability and not on transmitter release mechanisms.
Effects of tricyclic antidepressants on the content and metabolism of dopamine in the rat striatum
Authors: Ghosh P. K. , Hrdina P. D.
Published: April 2011

The effects of tricyclic antidepressants: imipramine (IMI), desmethylimipramine (DMI), and amitriptyline (AMI) on the levels and metabolism of dopamine (DA) in rat striatum were investigated. All three antidepressant drugs produced at 60 min a marked increase in striatal DA content. The DA-enhancing effect of DMI was dose dependent until a ceiling (about 140% increase) was reached. The time-course study of DMI (10 mg/kg) revealed a biphasic effect: an initial accumulation of DA peaking at 60 min followed by a decline in levels to about 20% of controls at 3 h after administration. In DMI-treated rats, homovanillic acid concentration was decreased to 58% at 60 min, but increased to 118% at 3 h, whereas 3,4-dihydroxyphenylacetic acid levels were unchanged at 60 min, but significantly suppressed at 3-h time interval. The observed effects of tricyclic antidepressants on striatal DA may be relevant to the beneficial effect of these compounds in Parkinson's disease.
The effect of ouabain and of Ca2+ deprivation on isoproterenol- and DBcAMP-stimulated protein secretion from the superfused rat parotid gland
Authors: Afari G. , Tenenhouse A. , Klein J.
Published: April 2011

Protein secretion from rat parotid slices was studied by measuring the rate of release of 3H-protein from tissue superfused with Krebs–Ringer bicarbonate medium. Isoproterenol (IPR) and dibutyryl 3′5′ cyclic adenosine monophosphoric acid (DBcAMP) stimulated the release of protein from parotid slices in the presence of extracellular calcium (10−3 M). Ouabain (10−3 M) potentiated the secretory response to IPR (10−5 M) and inhibited the response to DBcAMP (10−3 M) but itself did not stimulate protein release. In the absence of extracellular calcium, IPR caused a significantly greater protein secretion (p < 0.05) than in the presence of that ion. In contrast DBcAMP did not stimulate protein secretion in the absence of extracellular calcium. Isoproterenol increased cAMP concentration in the tissue whereas ouabain had no effect on the tissue cAMP concentration in the absence or presence of IPR. In contrast with adrenaline, isoproterenol does not alter the ATP content of the tissue.The distribution of [3H]DBcAMP in the tissue was not significantly different from that of [14C]sorbitol. Removal of extracellular calcium (with the addition of 10−3 M EGTA) or the addition of ouabain had no effect on the distribution of DBcAMP.These results suggest that the stimulation of protein release by DBcAMP is an extracellular (plasma membrane) effect and that this nucleotide does not mimic the effect of isoproterenol. It is also concluded that altering the intracellular Na+:K+ ratio by inhibition of an ouabain-sensitive Na+–K+-ATPase does not of itself cause protein release, but does, under certain conditions, augment the response to isoproterenol perhaps by increasing a Na+-dependent mobilization of Ca2+ from intracellular stores.
Reserpine-induced supersensitivity to the activation of cardiac glycogen phosphorylase by calcium
Authors: Hall Margaret A. , McNeill John H.
Published: April 2011

Rats receiving reserpine (2.5 mg/kg, 24 h before sacrifice) developed a supersensitivity to the phosphorylase activating effect of both noradrenaline and Ca2+. Supersensitivity to the inotropic and chronotropic effects of the agonists did not develop with this dose of reserpine. It is concluded that reserpine induced supersensitivity, as well as being dose and species dependent, is also dependent on the response measured. It is concluded further that the supersensitivity developed to noradrenaline may be due to an alteration in the responding system (in this case the phosphorylase activating system) to calcium.