bluuebunny/crossref_metadata_2025_split huggingface dataset:
IS GREATER FEMALE LONGEVITY A GENERAL FINDING AMONG ANIMALS?
Authors: SMITH DAVID W. E. 
Published: January 2008

Summary(A) There are data showing beyond question a gender gap, with women living longer than men, especially in economically developed societies. There is greater male vulnerability to the major causes of human death.(B) In lower animals there are data suggesting a female survival advantage to adult life in many species, but the observations do not consider longevity or survival to an advanced age.(C) In laboratory rodents kept under controlled conditions the relationship of sex to longevity is variable, with males sometimes showing greater longevity than females and with life span being dependent on factors like breeding and diet.(D) Similar genetic and hormonal processes operate in humans and in non‐human mammals including the genetic mechanism of sex determination, the hormonal consequences of sex determination, and the effects of hormones on processes which affect longevity such as cholesterol levels and immune functions.(E) Causes of death in humans and animals are different, and it seems unlikely, therefore, that the same mechanisms could be determinants of longevity in all mammalian species.(F) Human male and female longevity continue to change, and it is likely that the gender gap will narrow, with societal and medical changes in post‐industrial societies reducing the male disadvantages in behaviour and in the handling of cholesterol.(G) It remains an important question whether part of the gender gap seen in humans is based on other differences in the basic biology of males and females.
THE USE OF AN IRREVERSIBLE β‐ADRENORECEPTOR ANTAGONIST TO EXAMINE RESERPINE‐ AND HYPOTHERMIA‐INDUCED SUPERSENSITIVITY OF GUINEA‐PIG ATRIA
Authors: BROADLEY K. J. , NICHOLSON C. D. 
Published: January 2008

Positive inotropic and chronotropic responses of guinea‐pig isolated left and right atria respectively to the sympathomimetic amine orciprenaline were recorded.
2 Pretreatment of animals with reserpine for 3 days produced supersensitivity of both the inotropic and chronotropic responses. Lowering the bath temperature from 38° to 30°C produced supersensitivity of untreated atria to the inotropic responses only.
Irreversible β‐adrenoreceptor antagonism of orciprenaline by Ro 03‐7894 was demonstrated by a persistent depression of the maximum inotropic and chronotropic responses after a prolonged washout from the bath (3 h).
The depression of the maximum rate and tension responses by Ro 03‐7894 was less in atria from reserpinepretreated animals.
The maxima were also depressed less at the lower bath temperature of 30°C. However, when atria were cooled during the incubation with Ro 03‐7894, the maxima were still depressed to the 38°C level.
That these results suggest either a receptor proliferation or change in efficacy as possible mechanisms for reserpine‐ and hypothermia‐induced supersensitivity is discussed.
RESPONSES TO NORADRENALINE OF PORTAL VEIN STRIPS FROM NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS
Authors: HARRIS A. , SWAMY V. C. , TRIGGLE D. J. , WATERS D. H. 
Published: January 2008

Responses to noradrenaline of isolated portal vein strips from 5–7 week and 15–17 week Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) have been examined.
15–17 week SHR tissues exhibited a greater sensitivity (lower ED50) to noradrenaline but only at reduced Ca2+EXT levels.
pA2 values for the α‐adrenoreceptor antagonists WB 4101 and prazosin were significantly lower in 5–7 week SHR consistent with some change at the adrenoreceptor level.
Veins from SHR relaxed more rapidly in Ca2+‐free saline following removal of noradrenaline than did veins from WKY.
D600 is a competitive antagonist of the Ca2+EXT‐dependent component of the noradrenaline response but K1 values were not significantly different in SHR and WKY.
DENERVATION AND β‐ADRENORECEPTORS OF THE CAT NICTITATING MEMBRANE
Authors: VARMA D. R. , NICKERSON M. 
Published: January 2008

Dose‐response curves to the relaxant effects of isoprenaline, salbutamol, adrenaline and noradrenaline were determined on the partially contracted smooth muscles of the cat nictitating membrane following α‐adrenoreceptor blockade in order to test the hypothesis of a causal relationship between the inhibition of neuronal uptake and denervation super‐sensitivity.
Denervation did not produce super‐sensitivity of the nictitating membrane to the β‐adrenoreceptor‐mediated relaxant effects of any of the four agents studied.
The sensitivity of the inferior muscle was greater than that of the medial muscle to agents which were good substrates for neuronal uptake (adrenaline and noradrenaline) as well as to those which were not (isoprenaline and salbutamol).
Denervation did not alter the antagonist activity of β‐adrenoreceptor blockers propranolol (nonselective) and metoprolol (β1‐blocker) against isoprenaline or of H 35/25 (β2‐blocker) against salbutamol.
These results do not support the hypothesis of a causal relationship between inhibition of neuronal uptake and super‐sensitivity to sympathomimetic amines.
MUSCARINIC EFFECTS OF VARIOUS ISOARECAIDINE ESTERS IN SYMPATHETIC GANGLIA
Authors: PORSIUS A. J. , WILFFERT B. , LAMBRECHT G. , MOSER U. , MUTSCHLER E. 
Published: January 2008

The pressor effects of various tertiary and quaternary isoarecaidine esters in both pithed and anaesthetized rats are reported. In order to elucidate the mechanism of action, various experiments were carried out with the quaternary isoarecaidine methyl ester (Q‐4‐Me).
Treatment with mecamylamine, dexetimide, reserpine and phentolamine abolished or reduced the pressor response to Q‐4‐Me, whereas pretreatment with cocaine gave rise to a prolonged pressor effect. Plasma noradrenaline levels were significantly increased after the infusion of Q‐4‐Me.
From the results it can be concluded that the pressor effects brought about by the quaternary compounds can be attributed to a stimulation of nicotinic and muscarinic receptors in sympathetic ganglia. The consequences of interaction with muscarinic receptors predominate over the effects due to minimal interference with nicotinic receptors by the drug.
THE RESPONSE OF THE COSTO‐UTERINE MUSCLE OF THE RAT TO ADRENORECEPTOR AGONISTS DURING THE OESTROUS CYCLE: A COMPARISON WITH THE UTERINE HORN
Authors: HARTLEY MARGARET L. , PENNEFATHER JOCELYN N. 
Published: January 2008

Adrenoreceptors in the rat costo‐uterine muscle were compared with those in the uterine horn. The responses of electrically‐stimulated preparations of both tissues to isoprenaline and phenylephrine were investigated in the absence and presence of phentolamine and propranolol to block α‐ and β‐adrenoreceptors respectively. Preparations were taken from rats at known stages of the four‐day oestrous cycle.
Both adrenoreceptor agonists consistently inhibited contractions in both tissues; threshold sensitivity to isoprenaline was similar for both tissues and at all cycle stages. The same held true for phenylephrine, which was only approximately 1/400 as potent as isoprenaline. A generally similar pattern was observed when concentrations producing maximum inhibition were compared; however during proestrus, phenylephrine was more potent in producing maximal responses in uterine horns than in costo‐uterine muscles.
Phentolamine had no effect on inhibitory responses to isoprenaline in either tissue, nor to phenylephrine in costo‐uterine muscles, but slightly enhanced the inhibitory action of phenylephrine in uterine horns from proestrous rats. Propranolol blocked the inhibitory effects of both drugs, revealing an excitatory effect of phenylephrine in the uterine horns at proestrus.
These observations, and estimates of pA2 values for propranolol against both agonists, indicate that β‐adrenoreceptors insensitive to cyclical fluctuations in ovarian hormone levels, are predominant in the uterine horn and may be the exclusive adrenoreceptor present in the costo‐uterine muscle. In the uterine horn a small sub‐population of excitatory α‐adrenoreceptors, the presence of which is masked by β‐adrenoreceptors, can be demonstrated during proestrus. These receptors may be dependent upon the presence of the endometrium and/or the circular smooth muscle layer. The costo‐uterine muscle, which lacks excitatory α‐adrenoreceptors, could serve as a useful model of the longitudinal layer of the myometrium in investigations of drug actions at β‐adrenoreceptors.
A STUDY OF GASTRIC SECRETION IN DOGS USING PILOCARPINE
Authors: WISECARVER J. , ETZEL K. , MAGEE D. F. 
Published: January 2008

Pilocarpine (40 μg/min i.v.) stimulated acid and pepsin secretion from Heidenhain pouches but did not stimulate secretion from the innervated stomach.
Pilocarpine significantly increased acid secretion from the innervated main stomach after the vagal nerves were bilaterally blocked with lidocaine.
The effect of pilocarpine on secretion from the Heidenhain pouch was depressed by ganglionic blockade (hexamethonium), by dopamine and by isoprenaline.
The stimulatory action of histamine on gastric secretion from either pouch or gastric fistulae was uninfluenced by dopamine.
The action of pilocarpine was augmented by the muscarinic ganglionic stimulant AHR 602. Considering this effect, as well as the secretory depression of isoprenaline, pilocarpine resembles pentagastrin rather than methacholine in its action.
NON‐ATROPINIC ANTICHOLINERGIC ACTION OF QUINIDINE ON THE FERRET STOMACH
Authors: GRUNDY D. , ANDREWS P. L. R. , MITCHELL H. W. 
Published: January 2008

The effect of quinidine on the cholinergic response of the ferret gastric corpus was investigated in vivo and in vitro.
In vivo, the atropine sensitive contractions of the gastric corpus evoked by stimulation of the cervical vagus in the anaesthetized ferret were antagonized by quinidine (10–30 mg/kg).
In vitro, quinidine (10 μg/ml) antagonized the contractile response elicited by transmural stimulation (T.M.) of strips of corpus. At this dose of quinidine, the response to acetylcholine at doses adjusted to match the response to T.M. stimulation were unaffected. At higher doses of quinidine (50 μg/ml) the response to stimulation of the non‐cholinergic, non‐adrenergic inhibitory neurones was also antagonized.
These results indicate that, at low doses, quinidine has an inhibitory effect on the cholinergic neurones.
EXOGENOUSLY STIMULATED GASTRIC SECRETION IN DOGS AFTER GANGLION AND SYMPATHETIC BLOCKADE AND ANTRAL ACIDIFICATION
Authors: ETZEL K. , WISECARVER J. , MAGEE D. F. 
Published: January 2008

In conscious dogs with gastric fistulae, Heidenhain pouches and in some cases, innervated pyloric pouches, ganglionic blockade augmented Heidenhain pouch acid secretion only if the gastric fistula remained closed in animals receiving pentagastrin.
Ganglionic blockade depressed methacholine‐stimulated acid and pepsin secretion from the Heidenhain pouch whether or not the fistula was open.
Acidification of the antral pouch consistently augmented the acid and pepsin secretion from the Heidenhain pouch when either pentagastrin or methacholine was the stimulus. Ganglionic blockade prevented this.
NON‐SPECIFIC SUPERSENSITVITY IN RAT PAROTID SALIVARY GLANDS FOLLOWING PARASYMPATHECTOMY
Authors: POAT JUDITH A. , TEMPLETON D. 
Published: January 2008

The effect of parasympathetic denervation (Px) of the rat parotid salivary glands has been studied.
Px produced a significant reduction in wet and dry weight of the parotid gland compared with the intact contralateral control gland. The DNA content per gland was not reduced indicating that cell death had not occurred but that individual cells were smaller.
Supersensitivity to both cholinoreceptor and β‐adrenoreceptor stimulation resulted following Px and was observed as a decrease in the threshold dose and an increase in the maximum secretory response.
The supersensitivity to β‐adrenoreceptor stimulation was not accompanied by a change in cyclic AMP production but there was an increase in the density of β‐adrenoreceptor binding sites/mg membrane protein.
The relationship of this increased density of receptors to the observed supersensitivity is discussed.
HETEROGENEITY OF β‐ADRENORECEPTOR SUBTYPES IN THE HUMAN PLACENTA
Authors: BARNETT D. B. , COOK N. , NAHORSKI S. R. 
Published: January 2008

The human placenta is a rich source of β‐adrenoreceptors. However, previous work has provided conflicting evidence as to the predominant receptor subtype present. This study was designed to clarify this situation.
The radioligand 3H‐dihydroalprenolol (3H‐DHA) was used to identify β‐adrenoreceptor binding sites in membranes prepared from human placentae obtained immediately post partum from normal full term pregnancies.
3H‐DHA binding to human placental membranes was saturable, of high affinity and exhibited the pharmacological characteristics of a β‐adrenoreceptor. Displacement by β‐adrenoreceptor agonists suggested a predominant β1‐subtype with a hierarchy of potency isoprenaline > adrenaline > noradrenaline. Analysis of the displacement of the specific binding of 3H‐DHA by β‐adrenoreceptor antagonists yielded Hill plots with an apparent slope (nH) of one for the non selective antagonist (−)propranolol, and of less than one for the highly selective antagonists practolol (β1), and ICI 118,551 (β2) indicating a possible heterogeneity of binding sites.
A direct comparison of the displacement of 3H‐DHA binding by selective antagonists in the placenta with that occurring in rat and rabbit lung, further established that a mixture of β1‐ and β2‐adrenoreceptor binding sites was present.
Graphical analysis by Hofstee plot and computer assisted iterative curve fitting was used to further evaluate the displacement by the selective agents and established the presence of an heterogeneous population of β‐adrenoreceptor subtypes in the human placenta with approximately 65%β1 and 35%β2.
VALIDATION OF INDIRECT SYSTOLIC BLOOD PRESSURE MEASUREMENT IN ETHER ANAESTHETISED RATS
Authors: BORKOWSKI K. R. , QUINN P. 
Published: January 2008

Systolic blood pressures and plasma catecholamine concentrations were determined in conscious and ether‐anaesthetised male spontaneously hypertensive (SHR), Wistar‐Kyoto normotensive (WKY/N), Wistar (W) and Sprague‐Dawley (SD) rats.
When compared to conscious animals, plasma noradrenaline concentrations were significantly higher in all four strains of ether‐anaesthetised rats.
Only the SHR rats did not show an elevation in plasma adrenaline concentration when anaesthetised with ether.
A good correlation was obtained between systolic blood pressures measured indirectly, using a tailcuff method with two different sensors, in ether‐anaesthetised rats and pressures measured directly, via an indwelling carotid catheter, in conscious unrestrained animals.
It is concluded that, while ether anaesthesia elevates plasma catecholamine concentrations in rats, the increase in plasma catecholamines has little, if any, effect on indirect systolic blood pressure measurements.
β‐ADRENORECEPTOR ANTAGONISTS WITH MULTIPLE PHARMACOPHORES: PERSISTENT INHIBITION OF RAT HEART ADENYLATE CYCLASE
Authors: KUSIAK J. W. , PITHA J. 
Published: January 2008

β‐Adrenoreceptor antagonists containing several pharmacophores, so called alprenolol‐Jeffamines, were studied. These compounds are derived from JeffamineR NH2‐CH‐(CH3)‐CH2‐[‐O‐CH2‐CH(CH3)‐]n‐ NH29n = 2.6 ave. by substitution of nitrogen with 3‐(2‐allylphenoxy)‐2‐hydroxypropyl groups, which are part of the AlprenololR pharmacophore.
Alprenolol‐Jeffamines inhibited (‐)isoprenaline stimulated adenylate cyclase activity; the derivative with one pharmacophore was about 4‐fold and the derivative with two pharmacophores was about 17‐fold less potent than (+)alprenolol; the trisubstituted derivative which has one complete and two partial pharmacophores was ineffective.
The ratio of Ki's for inhibition of (‐)3H‐DHA binding and for inhibition of adenylate cyclase were approximately one for each derivative.
When (+)alprenolol‐Jeffamine derivatives were injected intraperitoneally into rats and heart membranes or homogenates were prepared 18–20 h afterwards, the mono, di, and trisubstituted derivatives, but not (+)alprenolol, inhibited bindng of (‐)3H‐DHA. This persistency pattern is different from that observed in vitro, where only di and trisubstituted derivatives are persistent. Slow metabolism/slow excretion of the monosubstituted derivative may be a source of the increased persistency in vivo.
In similarly prepared animals, the dose‐response curve for (‐)isoprenaiine stimulated adenylate cyclase was shifted to the right 3‐to‐4 fold for mono and disubstituted derivatives but was unaffected by (+) alprenolol and the trisubstituted derivative.
The results suggest that these derivatives interact with physiologically important β‐adrenoreceptors in vitro, and that, in vivo, they persistently block β‐adrenoreceptors and inhibit isoprenaline stimulated adenylate cyclase.
AUTONOMIC NEUROPATHY IN THE ALLOXAN‐DIABETIC RAT
Authors: TOMLINSON D. R. , YUSOF A. P. M. 
Published: January 2008

This study was designed to correlate functional and ultrastructural examination of the innervation of the atria and vas deferens of rats with long‐term alloxan‐induced diabetes mellitus.
After 7–8 months of diabetes the responses of preparations in vitro to nerve stimulation and to exogenous autonomic transmitter were compared with those from age‐matched controls.
Right atria from controls and diabetics were equally responsive to noradrenergic nerve stimulation and to exogenous noradrenaline. Left atria from diabetic rats were supersensitive to both noradrenaline and acetylcholine. The left atria gave normal inotropic responses to noradrenergic nerve stimulation but responses to cholinergic nerve stimulation were absent. The vasa deferentia from both groups gave similar responses to noradrenergic nerve stimulation and to noradrenaline.
The electron microscope revealed many abnormal, degenerate noradrenergic nerve profiles in both right atria and vas deferens. No cholinergic terminals were found in the right atria.
These findings indicate that this form of experimental diabetes causes parasympathetic denervation of the heart with some indications of degeneration of sympathetic nerves.
Comparison between the cardiovascular effects of 8‐hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐OH‐DPAT) and clonidine in the conscious sino‐aortic denervated rat
Authors: Petty M. A. , Kintz J. , Di Francesco G. F. , Fozard J. R. 
Published: January 2008

1 The purpose of this study was to investigate the role of an intact baroreceptor reflex mechanism in the expression of the cardiovascular response to 8‐OH‐DPAT and to determine whether there are any differences between the activation of central α2‐adrenoreceptors and 5‐HT1A receptors in this respect. To this end, the effects of 8‐OH‐DPAT and clonidine have been assessed on blood pressure, heart rate, ECG and cardiac contractility indices in conscious sino‐aortic baroreceptor denervated (SAD) rats and their sham‐operated controls.2 In both sham‐operated and SAD rats, intravenous (i.v.) administration of 8‐OH‐DPAT (32 μg kg−1) and clonidine (8 μg kg−1) produced falls in systemic blood pressure, left ventricular systolic pressure and dP/dtmax.3 8‐OH‐DPAT produced similar bradycardia in each group of rats; in contrast, clonidine had a greater effect in the SAD animals. Increases of the PQ interval mirrored the heart‐rate changes with both compounds.4 No significant changes in end diastolic blood pressure or in the myocardial contractility indices dP/dtmas/P and Vmax: were evident.5 This study provides support for the view that i.v. 8‐OH‐DPAT lowers blood pressure and heart rate through a central mechanism. The effects occur independently of an intact baroreceptor reflex and are not associated with effects on myocardial contractility. 8‐OH‐DPAT shows close qualitative similarities to clonidine in this model.
Comparison of the effects of phenoxybenzamine and uptake blockade on noradrenaline efflux from rabbit ear arteries evoked by field stimulation and propagated nerve impulses
Authors: Rand M. J. , Story D. F. , Sutton I. 
Published: January 2008

1 A comparison has been made of the effects of blockade of prejunctional α‐adrenoreceptors and blockade of transmitter noradrenaline uptake in segments of rabbit ear arteries subjected to field stimulation or neuronally propagated impulses.2 The relationship between evoked release and frequency of stimulation differed in artery segments subjected to field stimulation and those receiving propagated nerve impulses. However, the effectiveness of phenoxybenzamine in increasing stimulation‐induced efflux of radioactivity decreased as the frequency of stimulation increased in artery segments subjected to either field stimulation or neuronally propagated impulses.3 Blockade of neuronal and extraneuronal uptake had no effect on evoked efflux from field‐stimulated artery segments but it did produce a marked and significant enhancement of release evoked by propagated nerve impulses.
No evidence for more than one type of α1‐adrenoreceptor in rabbit pulmonary artery
Authors: Docherty J. R. 
Published: January 2008

1 The effects of the α‐adrenoreceptor antagonists, prazosin and yohimbine, have been examined on the isometric contraction of the rabbit pulmonary artery produced by α1‐adrenoreceptor agonists. Cocaine, corticosterone and propranolol were present throughout and either a single or two concentration‐response curve method was used.2 Prazosin and yohimbine competitively antagonized the responses to agonists but did not reveal differences between agonists.3 Using the single concentration‐response curve method, prazosin had pA2 values of 9.06 against clonidine and 8.76 against methoxamine.4 Using the two concentration‐response curve method the absolute pA2 values of prazosin (8.65 against phenylephrine, 8.78 against clonidine) and yohimbine (5.73 against phenylephrine, 5.72 against clonidine), as well as the relative potencies of the two antagonists (prazosin approximately 1000 times more potent than yohimbine), suggest that both agonists act on α1‐adrenoreceptors.5 There is no evidence from this study to support the suggestion that the rabbit pulmonary artery contains two subtypes of of α1‐adrenoreceptor.