bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the platelet phenolsulfotransferase involved in the sulfoconjugation of plasma catecholamines?
Authors: Romain Yveline , Demassieux Sylvain , D'Angelo Giovanni , Gyger Martin , Carrière Serge
Published: April 2011

Catecholamines are predominantly present in the sulfoconjugated forms in human plasma. Phenolsulfotransferase (EC 2.8.2.1), which catalyses the sulfation of phenolic compounds, is widely distributed in human tissues. In blood, a phenolsulfotransferase, more specific for catecholamine sulfation is found exclusively in platelets. Free and sulfoconjugated catecholamines were measured in plasma and platelets of healthy volunteers and compared with those present in patients with uremia or pheochromocytoma to determine the ability of platelet phenolsulfotransferase to sulfurylate plasma catecholamines. In patients with pheochromocytoma, the rise in free and sulfoconjugated plasma catecholamines is accompanied by a simultaneous rise of these molecules in platelets. In uremia, where the level of plasma catecholamines is normal, the rise in the sulfoconjugates is not accompanied by a concomitant increase in either free or sulfoconjugated catecholamines in platelets. Platelet phenolsulfotransferase activity remains unchanged in pheochromocytoma and uremia. These data indicate that the platelet phenolsulfotransferase is involved in the sulfation of the catecholamines present in platelets, but its contribution, if any, to the high level of sulfoconjugated catecholamines found in plasma is negligible. This assertion is confirmed by our observations in thrombocytopenic patients. Indeed, despite the very low number of platelets and the absence of plasma phenolsulfotransferase activity, thrombocytopenic patients have normal plasma levels of free and sulfoconjugated catecholamines.
Inhibition of release of a novel pituitary polypeptide, 7B2, follicle-stimulating hormone, and luteinizing hormone from rat anterior pituitary cells in vitro by human β-inhibin
Authors: Chan John S. D. , Deng Jie-Ying , Brar Anoop K. , Seidah Nabil G. , Chrétien Michel
Published: April 2011

We have recently purified a novel pituitary polypeptide designated 7B2. By raising polyclonal antibodies to a synthetic 7B2 fragment in rabbits, we have developed a sensitive and specific radioimmunoassay for this novel polypeptide, and it has been used for the study of the release of immunoreactive 7B2 from rat anterior pituitary cells in vitro. In addition, immunocytochemical study shows that 7B2 is present in the gonadotropin cells of rat anterior pituitary. The aim of the present studies is to investigate the effect of human β-inhibin, testosterone, and combined testosterone plus human β-inhibin on the induced release of immunoreactive 7B2, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in rat anterior pituitary cell culture in vitro. Our results show that both human β-inhibin and testosterone effectively suppress the stimulatory effect of luteinizing hormone-releasing hormone (LHRH) on immunoreactive 7B2, FSH, and LH release. The present data indicate that the regulation of secretion of 7B2 and pituitary gonadotropins may be under a similar type of feedback mechanism.
Effect of raised portal venous pressure and postocclusive hyperemia on superior mesenteric arterial resistance in control and adenosine receptor blocked state in cats
Authors: Lautt W. Wayne
Published: April 2011

Superior mesenteric arterial (SMA) blood flow was measured in pentobarbital-anesthetized cats using a noncannulating electromagnetic flowprobe. The selective adenosine antagonist 8-phenyltheophylline (8-PT) antagonized the dilator effect of infused adenosine but not isoproterenol. The vasodilation in response to reduced arterial perfusion pressure (autoregulation) was blocked by the adenosine receptor blockade, which also reduced the degree of postocclusive (1 min) hyperemia by one-half to two-thirds. The remainder of the hyperemia may have been due partially to adenosine, since exogenous adenosine still produced a small vasodilation (26%), so effects of endogenous adenosine could also still be expected to exert a small effect. Myogenic effects appear unlikely to be the mechanism of the small remaining hyperemia, since venous pressure increments within physiologically relevant ranges did not cause altered SMA conductance, and arterial dilation in response to large decreases in arterial pressure could be blocked by adenosine antagonism. Portal pressure was increased using hepatic nerve stimulation (8 Hz) to raise pressure from 7.0 to 12.4 mmHg (1 mmHg = 133.3 Pa). The small vasoconstriction seen in the SMA was due to the rise in systemic blood pressure, since prevention of a rise in SMA pressure prevented the response and 8-PT blocked the response (previously shown to block arterial pressure–flow autoregulation). An equal rise in PVP imposed by partial occlusion of the portal vein did not lead to changes in SMA vascular conductance. Thus, we conclude that within physiologically relevant ranges of arterial and portal venous pressure, the SMA does not show myogenic responses of the resistance vessels.
Possible involvement of serotonin receptors in the facilitatory effect of a hallucinogenic phenethylamine on single facial motoneurons
Authors: Penington Nicholas J. , Reiffenstein R. J.
Published: April 2011

2,5-Dimemoxy-4-methylamphetamine (DOM, "STP") is a potent hallucinogen, proposed to be a serotonin receptor agonist. Its effects have not previously been tested upon central neurons where serotonin is excitatory and serotonin antagonists are effective. Extracellular single unit recordings were obtained from facial motoneurons in anaesthetized rats, and drugs were applied from five-barrelled micropipettes by iontophoresis. Facial motoneurons were commonly silent. During subthreshold application of glutamate, firing could be induced by dopamine and DOM. As reported by others, serotonin and noradrenaline also excited facial motoneurons under these conditions. Methysergide antagonized responses to serotonin and DOM but not those to noradrenaline; methysergide could not usually discriminate between responses to serotonin and dopamine. Ketanserin reversibly antagonized (but could not discriminate between) responses to serotonin, dopamine, and noradrenaline. Chlorpromazine antagonized responses to dopamine at doses that did not alter serotonin-induced excitation, and responses to DOM were not reduced by doses of chlorpromazine, that had no local anaesthetic effect on action potentials elicited by DOM and serotonin. These results suggest that DOM is an agonist on at least one type of central serotonin receptor. This receptor may also be a ketanserin (5-HT2) binding site.
Pharmacological characterization of airway smooth muscle responses to antigen in ascaris-sensitive dogs
Authors: Kannan M. S. , Davis C. , Sankaranarayanan A. , Ladenius A. R. C. , Kannan L.
Published: April 2011

The dog model of ascaris airway sensitivity was chosen because of its frequency and its immunologic similarity to the human atopic asthmatic state. We studied the mediators of the antigen-induced airway response in vitro and the alterations in the in vivo and in vitro responsiveness to spasmogens evoked by antigen challenge. A myogenic basis of altered reactivity was suggested by the following: (i) tetrodotoxin-insensitive spontaneous active tone; (ii) phasic contractions of airway smooth muscle; and (iii) responsiveness to leukotrienes C4 and D4. The pharmacologic characteristics of the antigen-induced airway smooth muscle contraction in vitro were similar to those induced by arachidonic acid and the leukotrienes only in some respects but were clearly different from those induced by compound 48/80. This suggested a predominant role for arachidonate lipoxygenase products. Histamine apeared to play a minor role in the antigen response. Comparisons were made between antigen-induced responses of actively and passively sensitized airways tissues. In the latter, histamine release appeared to contribute to the initial antigen-induced contraction and, unlike in actively sensitized airways, the responses were easily densensitized to repeated challenge. Alterations of airway responsiveness were demonstrated in vivo to acetylcholine and 5-HT following antigen challenge of highly ascaris-sensitive dogs. In vitro studies of passively sensitized muscle showed selectively enhanced response to 5-HT following antigen challenge. These studies suport the presence of altered myogenic properties of airway smooth muscle and nonspecific increased airway responsiveness in this animal model.
Myocardial oxygen supply during hypocapnia and hypercapnia in the dog
Authors: Wexels Jan C.
Published: April 2011

It has been postulated that a coronary vasoconstriction during hypocapnia might be opposed by a compensating coronary vasodilatation due to impaired myocardial oxygen supply. The present study was performed first to examine whether a maximal decline in coronary sinus (CS) oxygen content was reached during hypocapnia. During hypercapnia a myocardial "over perfusion" has been demonstrated. The second purpose of the present study was to examine whether a myocardial "over perfusion" is essential to maintain a sufficient myocardial tissue oxygen supply during hypercapnia. Closed-chest dogs were anesthetized with pentobarbital and hypocapnia was induced by hyperventilation. Nitrogen gas and carbon dioxide could both be added to the inspiratory gas to create arterial hypoxemia (arterial So2 65%) and hypercapnia, respectively. Arterial hypoxemia during hypocapnia increased myocardial blood flow (MBF) by 50%, while CS So2 decreased significantly. The decrease in CS So2 demonstrates a reserve capacity of myocardial oxygen extraction during hypocapnia, thereby ruling out any major coronary vasoconstriction during hypocapnia. Hypercapnia during normoxemia increased MBF, myocardial oxygen delivery, and CS So2 substantially, but this was not observed when hypercapnia was created during arterial hypoxemia. From the present results we conclude that hypocapnia does not cause any major coronary vasoconstriction, while hypercapnia results in a myocardial "over perfusion," which is a luxury perfusion not essential to maintain sufficient myocardial oxygen supply during hypercapnia.
Effects of sulfhydryl reagents on nitroglycerin-induced relaxation of bovine coronary artery
Authors: Gruetter Carl A. , Lemke Sally M.
Published: April 2011

The mechanism whereby nitroglycerin relaxes vascular smooth muscle remains uncertain. A current hypothesis suggests that nitroglycerin reacts with critical cellular sulfhydryl groups to form an intermediate, which activates guanylate cyclase, resulting in cGMP accumulation and relaxation. This study investigated further the potential involvement of sulfhydryls in nitroglycerin-induced vascular smooth muscle relaxation by evaluating effects of a variety of sulfhydryl alkylating and reducing agents on responses to nitroglycerin and other relaxants in bovine coronary arterial strips submaximally contracted using 30 mM K. Whereas 10−4 M 5,5′-dithiobis-(2-nitrobenzoicacid), 10−5M N-ethylmaleimide, and 10−4M N-naphthylmaleimide did not affect nitroglycerin-induced relaxation, 10−4 M N-ethylmaleimide and 10−4 M ethacrynic acid significantly inhibited relaxation induced by nitroglycerin. Both ethacrynic acid and N-ethylmaleimide at 10−4 M also inhibited relaxation induced by sodium nitroprus-side. N-ethylmaleimide, but not ethacrynic acid, inhibited relaxation induced by isoproterenol and forskolin. Ethacrynic acid significantly reduced both relaxation and cGMP elevation induced by both 10−7 M nitroglycerin and 10−7 M sodium nitroprusside. Ethacrynic acid, but not N-ethylmaleimide, significantly reduced relaxation induced by 8-Br-cGMP. Pretreatment with the sulfhydryl-containing agents N-acetylcysteine, 2-mercaptoethanol, or dithiothreitol, at 10−3 M did not affect nitroglycerin-induced relaxation in nontolerant arteries. Similarly, N-acetylcysteine and dithiothreitol did not alter the depressed responses to nitroglycerin in arteries in which tolerance to nitroglycerin was induced in vitro. A slight but statistically significant reversal of nitroglycerin-tolerance occurred after treatment of tolerant arteries with 2-mercaptoethanol. As none of the sulfhydryl alkylating agents tested inhibited selectively nitroglycerin-induced relaxation, and none of the sulfhydryl-containing agents markedly enhanced nitroglycerin-induced relaxation in either nontolerant or tolerant arteries, the results provide little evidence to support the hypothesis that critical sulfhydryl groups are involved specifically in nitroglycerin-induced relaxation of arterial smooth muscle. The results do suggest that ethacrynic acid may selectively inhibit relaxation induced in bovine coronary artery by relaxants that act by activating guanylate cyclase, and that the inhibition by ethacrynic acid may involve two mechanisms, an inhibition of guanylate cyclase activation and an inhibition of the relaxant effect of cGMP.
Lack of effect of antagonists on serotonin-induced inhibition in rat hippocampus
Authors: Penington N. J. , Reiffenstein R. J.
Published: April 2011

Four putative central nervous system 5-hydroxytryptamine antagonists, methysergide, cyproheptadine, metergoline, and ketanserin and also lysergic acid diethylamide were applied by iontophoresis to firing CA1 hippocampal pyramidal cells to test their action on the inhibition produced by 5-hydroxytryptamine. In contrast to a previous report, none of these peripherally active 5-hydroxytryptamine antagonists altered the inhibitory response to submaximal doses of 5-hydroxytryptamine, but they did block after-excitations that followed the inhibitions. All the antagonists and lysergic acid diethylamide produced a depression of firing. When picrotoxin was used to drive the cells, 5-hydroxytryptamine was still able to produce a normal inhibition. The results of this study suggest that CA1 hippocampus is another structure, innervated by serotonergic neurones, where all (peripherally active) serotonin antagonists tested to date are ineffective against 5-hydroxytryptamine induced inhibition.
Excitation–contraction coupling in isolated adult ventricular myocytes from the rat, dog, and rabbit: effects of various inotropic interventions in the presence of ryanodine
Authors: Horackova Magda
Published: April 2011

Enzymatically isolated ventricular cells from rats, dogs, and rabbits were electrically stimulated and their membrane potentials were recorded simultaneously with their contractions. Specific pharmacological interventions were used to assess the relative roles of transsarcolemmal Ca2+ entry and the Ca2+ release by the sarcoplasmic reticulum in activating contractions, in these myocytes. We used ryanodine and caffeine to influence Ca2+ release by the sarcoplasmic reticulum, BAY K 8644 and epinephrine to increase Ca2+ entry through Ca2+ channels, and veratridine, ouabain, and monensin to increase Ca2+ entry through Na+–Ca2+ exchange. Ryanodine (1 μM) completely inhibited the shortenings in rat and dog myocytes, but the contractions in rabbit myocytes were much less sensitive to this alkaloid. Similar inhibitory effects of ryanodine were observed in the presence of various inotropic agents with two exceptions: caffeine's effect on the dog myocytes was relatively insensitive to ryanodine and the long-lasting tonic contractions that veratridine triggered in the myocytes of all three species remained completely unaffected by ryanodine. The data indicate that contractile activation in rat and dog ventricular cells is strongly dependent on Ca2+ release from the sarcoplasmic reticulum, while contractility in rabbit myocytes seems to be more dependent on Ca2+ entry through the sarcolemma. The ryanodine-resistant tonic contractions triggered in the myocytes of all three species in the presence of veratridine may be activated by an increased Ca2+ entry via Na+–Ca2+ exchange.
Stimulation of aortic tissue calcium uptake by an extract of spontaneously hypertensive rats erythrocytes possessing hypertensive properties
Authors: Wright G. L. , Rogerson M. E. , McCumbee W. D.
Published: April 2011

In earlier reports we have described the isolation of a fraction from the erythrocytes of spontaneously hypertensive rats that produced hypertension when administered to normotensive rats. In addition, it was found that the fraction stimulated the uptake of "lanthanum-resistant" calcium by aortic rings excised from normotensive rats. In these studies we have found that the fraction causes a greater increase in the in vitro uptake of calcium by aortic tissue than that produced by depolarization of the tissue with high K+ or the receptor-mediated influx of calcium induced with norepinephrine. The hypertensive fraction appeared to be more effective in promoting increased calcium uptake in rabbit than in rat aortic tissue, suggesting that significant differences in tissue sensitivity to the active compound(s) may exist between species. In addition, we obtained evidence indicating that the tissue sensitivity to the action of the hypertensive fraction was greater in aortae from spontaneously hypertensive rats than from those of normotensive animals. Attempts to block the action of the hypertensive fraction with verapamil, nifedipine, and sodium nitroprusside had no significant effect on the elevation in tissue calcium. It was found, however, that the action of the hypertensive fraction was temperature dependent with reduced activity at lower temperatures. The data suggest that a compound(s) is present in the erythrocytes of rats that may have a marked effect on vascular tissue metabolism of calcium.
Chloride removal and excitation–contraction coupling in guinea pig ileal smooth muscle
Authors: Rangachari P. K. , Triggle C. R.
Published: April 2011

The effect of extracellular Cl [Formula: see text] removal on contractions evoked by a selective muscarinic agonist, cis-2-methyl-4-dimethylaminomethyl 1,3-dioxolane methiodide (CD), and high K+ depolarizations in the isolated guinea pig ileal longitudinal muscle was studied. The replacement of [Formula: see text] with impermeant anions, such as isethionate (Ise−), was found to selectively inhibit a portion of the initial phasic response to K+ and CD, leaving the secondary and sustained tonic responses unchanged. In Ca2+-free solutions, the loss of contractile responses to high K+ was faster and more pronounced in Cl−-free compared with Cl−-containing solutions. Furthermore, the uptake of Ca2+, as represented by 45Ca2+, from the saline solution was delayed and reduced in Ise−-containing [Formula: see text]-free solutions. Replacement of [Formula: see text] with other impermeant anions, such as gluconate and methylsulphate, had a similar action on contractile activity as for Ise− replacement. [Formula: see text] replacement with permeant anions, such as nitrate, however, did not significantly inhibit the phasic response and sometimes increased the tonic response to K+. These results indicate that there is a [Formula: see text]-dependent Ca2+ pool in the guinea pig ileal longitudinal muscle and we speculate that this [Formula: see text]-dependent Ca2+ pool is associated with membrane structures, such as calveolae, which would thus offer a degree of protection to depletion by removal of extracellular Ca2+. Overall, these data suggest that agonist responses in guinea pig ileal longitudinal muscle preparations utilize at least three Ca2+ pools: a [Formula: see text]-sensitive pool supplying Ca2+ primarily for phasic contractions, a [Formula: see text]-insensitive pool supplying Ca2+ for tonic and phasic contractions, and an extracellular pool that is most sensitive to organic Ca2+ channel antagonists such as D-600 and supplies Ca2+, presumably entering the cell through voltage-operated Ca2+ channels, for the tonic contractions.
Effect of ovine conceptus and endometrial secretory products on luteal progesterone production in vitro
Authors: Beckner D. W. , Manns J. G.
Published: April 2011

The objectives of this study were the following: (i) to determine if ovine conceptus secretory products are directly luteotrophic to luteal tissue in vitro and (ii) to determine if ovine conceptus secretory products stimulate endometrial tissue to secrete a luteotropin in vitro. Conceptus-conditioned medium (CCM) was prepared by incubating day 14 ovine conceptuses in minimal essential medium (MEM) for 24 h and harvesting the supernatant. Endometrium-conditioned CCM (E-CCM) and endometrium-conditioned medium (ECM) were prepared by incubating dispersed ovine endometrial cells from day 9–10 cycling ewes in CCM or MEM, respectively, for 16 h and harvesting the supernatants. Media, conditioned as described, were incubated at various dilutions with dispersed luteal cells from day 9–10 cycling ewes for 90 min or 6 h in the absence or presence of 50 ng/mL ovine luteinizing hormone (oLH). CCM did not alter progesterone (P4) production in the 90-min incubation but did increase (p < 0.05) P4 production in the 6-h incubation (1:4, 1:8, 1:16 dilutions). When coincubated with oLH, CCM did not increase P4 production above that stimulated by oLH alone. The effect of E-CCM was similar to CCM or ECM and did not differ significantly from basal. It is concluded that the day 14 ovine conceptus does secrete a factor that is able to directly stimulate P4 secretion by luteal cells in a 6-h, but not a 90-min, incubation. Conceptus secretory products did not stimulate endometrial cells to secrete a luteotropin. The data are consistent with the suggestion that the luteotrophic factor secreted by the conceptus is a prostaglandin of the E series.
Cultured juxtaglomerular cells: production and localization of renin
Authors: Lacasse J. , Kreft C. , Gutkowska J. , Genest J. , Cantin M.
Published: April 2011

Trypsin- or collagenase-dispersed renal cortical cells from newborn mice were filtered and cultured. The cultures comprised 25% juxtaglomerular cells as identified by immunocytochemistry. Renin was measured by radioimmunoassay in the culture medium and in the cells at various time intervals. This in vitro system was responsive to isoproterenol, which stimulated renin release in a dose-dependent manner.
Comparative aspects and temperature dependence of [3H]1,4-dihydropyridine Ca2+ channel antagonist and activator binding to neuronal and muscle membranes
Authors: Rampe D. , Luchowski E. , Rutledge A. , Janis R. A. , Triggle D. J.
Published: April 2011

Binding of [3H]nitrendipine, [3H]nimodipine, and (+)[3H]PN 200-110 to microsomal preparations of guinea pig smooth and cardiac muscle and brain synaptosomes revealed high affinity interaction with KD values in the sequence, (+)PN 200-110 > nitrendipine > nimodipine. Bmax values for a particular tissue were independent of the 1,4-dihydropyridine employed in radioligand binding at 25 °C. The temperature dependence of [3H]nitrendipine binding in cardiac and smooth muscle microsomal preparations and brain synaptosomes was measured from 0° to 37 °C and for skeletal muscle preparations from 0° to 30 °C. Bmax values increased with temperature for cardiac membranes, but did not vary in other tissues, van't Hoff plots were nonlinear in all tissues, enthalpy and entropy changes becoming increasingly negative with increasing temperature. Competition binding of the activator–antagonist enantiomeric 1,4-dihydropyridine pairs of Bay k 8644 and PN 202-791 for [3H]nitrendipine in smooth muscle did not reveal significant thermodynamic differences between activator and antagonist molecules.
Bethanidine increased Na+ and Ca2+ currents and caused a positive inotropic effect in heart cells
Authors: Bkaily G. , Payet M. D. , Benabderrazik M. , Renaud J.-F. , Sauvé R. , Bacaner M. B. , Sperelakis N.
Published: April 2011

The effects of bethanidine sulphate, a pharmacological analog of the cardiac antibrillatory drug, bretylium tosylate, were studied on action potentials (APs) and K+, Na+, and Ca2+ currents of single cultured embryonic chick heart cells using the whole-cell current clamp and voltage clamp technique. Extracellular application of bethanidine (3 × 10−4 M) increased the overshoot and the duration of the APs and greatly decreased the outward K+ current (IK) and potentiated the inward fast Na+ currents (INa) and the inward slow calcium current (ICa). However, intracellular introduction of bethanidine (10−4 M) blocked INa. In isolated atria of rat, bethanidine increased the force of contraction in a dose-dependent manner. These findings suggest that when applied extracellularly, bethanidine exerts a potentiating effect on the myocardial fast Na+ current and slow Ca2+ current and an inhibitory effect of IK. The positive inotropic effect of bethanidine could be due, at least in part, to an increase of Ca2+ influx via the slow Ca2+ channel and the Na–Ca exchange. It is suggested that the decrease of IK by bethanidine may account for its antifibrillatory action.
Postnatal development of β-adrenergic response in ventricular muscle of the rat heart
Authors: Vornanen Matti
Published: April 2011

In adult mammalian, heart responses to β- and α-adrenergic stimulation are different: the β-type effect exhibits a larger increase of relaxation than of contraction, while the α-stimulation has no selective influence on relaxation. The present results show that the effect of isoprenaline (ISO) on the neonatal rat heart during the 1st postnatal week is not a typical β-effect in that the relaxant influence of β-stimulation is lacking. During the 2nd and 3rd postnatal weeks the typical β-response, with improved relaxation, gradually appears. The absence of the typical β-effect is not caused by the lack of β-receptors or cAMP-dependent phosphorylation reactions because in other respects, the positive inotropic effect of ISO is well developed at the moment of birth. In addition to these qualitative changes, also prominent quantitative changes occurred in the ISO response. The dose–response curves were shifted to the right with advancing age, suggesting reduced β-agonist potency of the maturing tissue. The developed tension (Tmax) abruptly increased between the 12th and 17th postnatal days and then steeply declined during the next 2 weeks. Changes in Tmax correlated fairly well with the general ability of the tissue to generate extra force, as expressed by rest-dependent potentiation of twitch. However, during the 2nd postnatal week cardiac tissue seemed to be subsensitive to ISO, since all contractile parameters except T′max were depressed. The results suggest that the postnatal changes in β-response are primarily determined by alternations in the electromechanical coupling process of the developing tissue, and less by the proper adrenergic mechanisms.
Effect of nitroglycerin and ibuprofen on left ventricular topography and rupture threshold during healing after myocardial infarction in the dog
Authors: Jugdutt Bodh I.
Published: April 2011

The effect of nitroglycerin and ibuprofen, given between 2 and 7 days after left anterior descending coronary artery ligation, on the mechanical resistance of the infarcted left ventricle to rupture or the rupture threshold (balloon technique), and on topography (computerized planimetry) and function (two-dimensional echocardiography) at 7 days (n = 32) and 42 days (n = 34) postligation was studied in 66 dogs randomly allocated to sham (no infarction, n = 22) and infarction subgroups (15 controls; 15 received nitroglycerin, 30 mg oral isosorbide dinitrate b.i.d; 14 received ibuprofen, 200 mg t.i.d orally). Nitroglycerin decreased mean arterial and left atrial pressures, decreased diastolic cross-sectional area, and improved systolic function, while ibuprofen increased diastolic area. Infarction subgroups showed infarct shrinkage and more infarct hydroxyproline at 6 weeks. Compared with shams, all infarct subgroups showed early expansion and thinning, with further marked late thinning in controls. Nitroglycerin produced less expansion and thinning both at 1 and 6 weeks, while ibuprofen produced marked early thinning. Rupture threshold was less at 6 weeks than 1 week with controls and ibuprofen but remained unchanged with nitroglycerin. Passive prerupture stiffness was less at 6 weeks than at 1 week in controls but remained unchanged with nitroglycerin and ibuprofen. Thus, reduced expansion and thinning with nitroglycerin during the first week after infarction improved function, mechanical strength, and resistance to distension at 6 weeks.
Attenuation of pulmonary and systemic vasoconstriction with pentoxifylline and aminophylline
Authors: Hakim T. S. , Petrella J.
Published: April 2011

The effects of acute administration of therapeutic doses (1–10 mg/kg) of pentoxifylline and aminophylline on the resistance of the systemic and pulmonary circuits in anaesthetized dogs and pigs were tested. During room air breathing, neither of the two substances caused a significant change in systemic vascular resistance (SVR) or pulmonary vascular resistance (PVR).During hypoxia (10% O2 and nitrogen), however, both substances caused a significant reduction in PVR (p < 0.05) without affecting SVR. The largest dose of pentoxifylline decreased PVR from 7.8 ± 2.8 to 4.4 ± 1.5 in dogs and from 9.9 ± 1.4 to 5.8 ± 0.6 mmHg∙L−1∙min in pigs. Aminophylline was equally effective and selective in lowering PVR but not SVR during hypoxia. When SVR was elevated in dogs by continuous infusion of angiotensin, pentoxifylline lowered SVR from 139 ± 27 to 83 ± 20 mmHg∙L−1∙min (p < 0.05). The simultaneous small elevation in PVR during angiotensin infusion was also attenuated to base-line value by pentoxifylline injection. These results suggest that xanthines, in therapeutic doses, can have a profound vasodilator effect on either the systemic or on the pulmonary circuit, only wherever the vessels are constricted. The vasodilatory effect of pentoxifylline is viewed as a second beneficial effect besides the benefit derived from its action on erythrocyte deformability.
Elementary properties of cardiac calcium channels: a brief review
Authors: Hess Peter
Published: April 2011

This article reviews the new insight into the function of cardiac calcium channels made possible by electrophysiological recordings from single cells and single channels. The unitary properties of the two different types of cardiac calcium channels are discussed and contrasted, and special emphasis is given to the mechanisms of channel permeation, gating, and modulation by exogenous and endogenous ligands.
Hypothalamic α-adrenergic blockade modifies drinking and blood pressure responses to central angiotensin II in conscious rats
Authors: Jones D. L.
Published: April 2011

These experiments investigated in the awake rat the involvement of noradrenergic projections to the rostral hypothalamus in the drinking and pressor responses elicited by intracerebroventricular (i.c.v.) injections of 25 ng of angiotensin II. Phentolamine mesylate in doses of 2.5–125 μg injected into the rostral hypothalamus produced a dose-dependent depression of both the drinking and pressor responses elicited by i.c.v. administration of angiotensin II. A paradoxical increase in heart rate was associated with a decrease in pressor responses with increasing doses of phentolamine. This response was due to tissue injections, since pretreatment by injecting 12.5 μg of phentolamine into the ventricle did not block either the cardiovascular or drinking responses to i.c.v. injections of angiotensin II. Yohimbine (0.33–3.3 μg), DL-propranolol (25 μg), and atenolol (25 μg) did not, but prazosin (0.7 μg) did significantly alter the pressor responses. Although yohimbine also was without effect on drinking, prazosin reduced the drinking responses. These results suggest that α1-adrenergic receptors in the rostral hypothalamus are involved in the control of both the drinking and pressor responses elicited by i.c.v. injections of angiotensin II. In the case of propranolol and atenolol, β-adrenergic receptors altered only the drinking response in a nonspecific manner by eliciting competing behaviors. Whether they are involved in modifying the drinking response only remains to be demonstrated.
Contraction of guinea pig trachea by epidermal growth factor – urogastrone
Authors: Patel P. , Itoh H. , Lederis K. , Hollenberg M. D.
Published: April 2011

To evaluate further the action of epidermal growth factor – urogastrone (EGF–URO) in smooth muscle systems, we examined the effect of the peptide on guinea pig tracheal strips. The cumulative addition of EGF–URO to the organ bath resulted in a concentration-dependent tonic contraction without tachyphylaxis. The half-maximal contraction was obtained at 13 ± 3 ng/mL EGF–URO (2 nM). The maximum contraction at 100 ng/mL approached 60% of that induced by 1 μM histamine. No significant difference in the EGF–URO-induced contraction was observed in the presence or absence of a functional epithelium, Preincubation with 1 μM indomethacin for 20 min abolished the action of EGF–URO. The contractile effect of EGF–URO was not affected by yohimbine, propranolol, atropine, tetrodotoxin, and esculetin. However, mepacrine caused inhibition by 37 ± 7% (mean ± SEM for n = 3). Verapamil (10 μM) inhibited the EGF-induced response by 62 ± 5% (mean ± SEM for n = 4); the response was also absent in Ca-free (1 mM EGTA) buffer. However, the response was restored after the readdition of calcium. Our results suggest that EGF–URO can modulate tracheal smooth muscle contractility via a cyclooxygenase product and raise the possibility that EGF–URO might play a role in controlling pulmonary smooth muscle tone in vivo.
Sheep testicular gonadotropin binding sites: characterization and changes with surgical shortening of the scrotum
Authors: Yarney T. A. , Sanford L. M. , Sairam M. R.
Published: April 2011

Gonadotropin receptors in previously frozen (−70 °C) sheep testicular tissue were characterized, and methods of assessment of receptor binding activity were established and applied to an investigation of testicular function in the short scrotum ram. Binding of 125I-labelled ovine luteining hormone (125I-oLH) and 125I-labelled ovine follicle-stimulating hormone (125I-oFSH) to testicular membranes was highly specific and saturable. Uptake of labelled gonadotropins was proportional to the amount of membrane protein, with 125I-oFSH showing greater specific binding. Initial association of 125I-oLH with binding sites was comparable at 4, 25, and 34 °C; with prolonged incubation, maximal binding occurred at 4 °C. Equilibrium was achieved in 8 h at 34 °C and in 16 h at 25 and 4 °C. In contrast, the temperature-dependent association of LH with rat testicular membranes was greater at 25 than at 4 °C. The rate of association of 125I-oFSH to binding sites was proportional to incubation temperature, with equilibrium being achieved in 2 h at 34 °C and in 16 h at 25 °C; binding at 4 °C was slow and still increasing by 48 h. Binding of radioactive and nonradioactive oLH and oFSH was hormone specific and increased in a dose-dependent manner until saturation occurred. Shortening the scrotum of adult rams led to reductions (p < 0.05) in testicular weight (60%) and in the number of LH (55%) and FSH (90%) binding sites per testis, with no apparent change in serum testosterone concentration. Results demonstrate that gonadotropin receptors in frozen-stored sheep testis tissue can be quantitated and are greatly reduced in number with testicular heat stress.
The development of voltege-dependent ionic conductances In murine spinal cord neurones in culture
Authors: Krieger C. , Sears T. A.
Published: April 2011

The development of voltage-dependent ionic conductances of foetal mouse spinal cord neurones was examined using the whole-cell patch-clamp technique on neurones cultured from embryos aged 10–12 days (E10–E12) which were studied between the first day in vitro (V1) to V10. A delayed rectifier potassium conductance (IK) and a leak conductance were observed in neurones of E10.V1, E11, V1, and E12, V1 as well as in neurones cultured for longer periods. A rapidly activating and inactivating potassium conductance (IA) was seen in neurones from E11, V2 and E12, V1 and at longer times in vitro. A tetrodotoxin (TTX) sensitive sodium-dependent inward current was observed in neurones of E11 and E12 from V1 onwards. Calcium-dependent conductances were not detectable in these neurones unless the external calcium concentration was raised 10- to 20-foid and potassium conductances were blocked. Under these conditions calcium currents could be observed as early as E11, V3 and E12, V2 and at subsequent times in vitro. The pattern of development of voltage-dependent ionic conductances in murine spinal neurones is such that initially leak and potassium currents are present followed by sodium current and subsequently calcium current.
Dose response of luteinized porcine granulosa cells in vitro to prolactin: dependency on pre-exposure to human chorionic gonadotrophin
Authors: Chedrese Pedro J. , Rajkumar Kadaba , Ly Hoa , Murphy Bruce D.
Published: April 2011

This study examined the hypothesis that human chorionic gonadotrophin (hCG) increases prolactin (PRL) stimulation of the utilization of lipoprotein-borne cholesterol by pig luteinized granulosa cells in culture. These cells, which luteinize in culture, were harvested from 6-mm or greater diameter follicles and cultured in the presence of 1% fetal calf serum and 1 μ/mL insulin for 48 h. On the third day, the media were replaced with fresh serum-free media, with the same dose of insulin, and on the following day (day 4) the media were replaced with serum- and insulin-free media. At this time (day 4) hCG was added to some cultures. On day 5, cells from the group with hCG and cells from the group without hCG were treated with graded doses of ovine PRL (0.1–3.0 μg/mL). To a second set of cells, likewise treated, 100 μg of porcine low density lipoprotein (LDL) was added. Two days later (day 7) media were sampled and replaced with media alone or media containing hormones and (or) LDL. On day 9 cultures were terminated. In the cells pre-exposed to hCG, PRL (1 μg/mL) in the presence of LDL increased progesterone production 1.7-fold (p < 0.01) on day 7 and 2.2-fold (p < 0.01) on day 9. In the granulosa cells in culture pre-exposed to hCG, the effect of PRL on LDL utilization was dose dependent and saturable at 1 μg/mL on days 7 and 9. We conclude that brief pretreatment of luteinized pig granulosa cells with hCG results in a dose-dependent PRL-induced utilization of LDL for progesterone synthesis.
Nitric oxide-induced vasodilation of organic nitrate-tolerant rabbit aorta
Authors: Slack Christopher J. , McLaughlin Brian E. , Nakatsu Kanji , Marks Gerald S. , Brien James F.
Published: April 2011

It is postulated that the organic nitrate vasodilator agents, including glyceryl trinitrate (GTN) and isosorbide dinitrate (ISDN), are prodrugs, such that biotransformation to the active inorganic metabolite, nitric oxide (NO), occurs prior to the onset of vasodilation. Furthermore, it is proposed that organic nitrate tolerance in vascular tissue involves decreased formation of NO. To test this latter hypothesis, we examined vasodilation induced by NO, GTN, and ISDN in non-tolerant, GTN-tolerant, and ISDN-tolerant rabbit aortic rings (RARs). Isolated RARs were contracted submaximally with phenylephrine; the time of onset of relaxation and percent relaxation of tissue were determined in response to NO (0.3 μM), GTN (0.03 μM), and ISDN (0.12 μM) before and after a 1-h treatment with 500 μM GTN, 500 μM ISDN, or buffer only. The data demonstrated that the response to NO was not changed in GTN-tolerant and ISDN-tolerant tissues, in which there was virtually no GTN-induced or ISDN-induced relaxation. These results are consistent with the postulate that organic nitrate vasodilator drugs must undergo biotransformation to NO before vasodilation can occur and that the mechanism of organic nitrate tolerance involves decreased formation of NO.
Sensitivity changes to inotropic agents in rabbit atria after chronic experimental diabetes
Authors: Grassby Paul F. , McNeill John H.
Published: April 2011

The effect of experimental diabetes on the sensitivity of isolated left atrial strips to inotropic agents was investigated in rabbits made diabetic with alloxan. After 4 weeks of diabetes no change in sensitivity was detected in response to isoproterenol or ouabain. In contrast, 15 weeks of diabetes induced a decreased sensitivity to β-adrenergic stimulation, exhibited as a shift to the right in concentration–response curves obtained in response to isoproterenol and noradrenaline. In addition, after 15 weeks of diabetes the inotropic response to ouabain was depressed, and a small decrease in sensitivity was detected in response to forskolin. In contrast, no significant changes in the concentration–response curves obtained from α-adrenergic stimulation by phenylephrine or calcium chloride were detected. Unlike the streptozotocin diabetic rat, which exhibits low serum thyroid hormone levels, no changes in serum thyroid hormones were detected in the alloxan diabetic rabbit. It is suggested that the increased inotropic sensitivity to α-adrenergic agonists observed in the diabetic rat, but not in the rabbit, may be due to low serum thyroid hormone levels. In contrast, the deleterious effects of diabetes on β-adrenergic and ouabain sensitivity occur independently of changes in serum thyroid hormones.
Characterization of a developmentally transient adrenergic depolarizing response in cultured locus coeruleus neurons
Authors: Finlayson Paul G. , Marshall Kenneth C.
Published: April 2011

The effects of iontophoretically applied noradrenaline have been tested on intracellularly recorded locus coeruleus neurons grown in explant cultures from neonatal mice. In addition to hyperpolarizing responses mediated by α2-adrenergic receptors, as observed in locus coeruleus neurons in vivo and in brain slices from adult animals, α1-mediated depolarizations were observed to succeed the initial hyperpolarizations in some cultures. It was shown that the depolarizing responses were only present in younger cultures, i.e., less than 26 days in vitro. In cultures less than 20 days old, all cells displayed the biphasic hyperpolarizing-depolarizing responses. Both components of the response appear to be direct, since they were present when synaptic transmission was blocked by including tetrodotoxin or by altering divalent cations in the perfusate. The depolarizing responses were frequently reduced in solutions with altered divalent cation content, and this might reflect a calcium dependency of this response. The hyperpolarizing and depolarizing components of the responses to noradrenaline were progressively blocked by increasing concentrations of the selective antagonists yohimbine and prazosin, respectively, in the dose ranges of 100 nM – 1 μM (yohimbine) and 20–200 nM (prazosin). Recent results from electrophysiological studies of locus coeruleus neurons in brain slices suggest that similar changes occur in the animal as well as in culture. It is possible that the transient depolarizing responses reflect a developmentally important enhanced responsiveness of locus coeruleus neurons during the early postnatal period.
Responses of the isolated rectum of the rainbow lizard (Agama agama) to sympathomimetics
Authors: Inyang A. L. , Okpako D. T.
Published: April 2011

The relaxant effects of isoprenaline, noradrenaline, and adrenaline on the isolated rectum of the rainbow lizard (Agama agama) were studied. Responses were measured as a reduction of carbachol-induced contractions for each sympathomimetic agent. Isoprenaline, adrenaline, noradrenaline produced a dose-dependent relaxation of this preparation and the order of potency was as given. The pD2 value of 8.15 ± 1.88 obtained for isoprenaline was significantly different (p < 0.05) from those for adrenaline (5.80 ± 0.90) and noradrenaline (5.25 ± 1.18). H35/25, propranolol, and practolol competitively antagonized the relaxant effects of isoprenaline on the isolated lizard rectum. The pA2 values for these β-adrenoceptor antagonists did not differ significantly (at p < 0.05). α-Adrenoceptor antagonists, phentolamine and phenoxybenzamine, failed to alter the relaxant responses of these sympathometics to any appreciable extent. These results are interpreted to suggest that the relaxant effect produced by these sympathomimetics are mediated predominantly by β-adrenoceptors that are not significantly differentiated into subtypes, α-Adrenoceptors in this preparation contribute minimally to the observed inhibitory response following sympathomimetic stimulation.Key words: sympathomimetics, lizard rectum, inhibitory response, β-receptors, α-receptors.
Noradrenaline turnover in brown adipose tissue and the heart of fed and fasted golden hamsters
Authors: Trayhurn P. , Howe A.
Published: April 2011

The effect of fasting on sympathetic activity in tissues of the golden hamster has been investigated using measurements of noradrenaline turnover. Fasting for 60 h did not have a significant effect on noradrenaline turnover, both fractional and total, in brown adipose tissue or the heart. Fasting did, however, result in a functional atrophy of brown adipose tissue; tissue weight, protein content, and cytochrome oxidase activity were each reduced after a 60-h fast. These results suggest that the atrophy of brown adipose tissue induced by fasting in the golden hamster does not relate to a major decrease in sympathetic activity. The findings add further support for the view that the thermogenic capacity of brown adipose tissue is not primarily dependent on sympathetic activity in the golden hamster.
The 1988 Stevenson Memorial Lecture. Physiological responses to severe hypoxia in man
Authors: West John B.
Published: April 2011

Recent measurements at extreme altitude and in low pressure chamber simulations have clarified the human responses to extreme hypoxia. Man can only tolerate the severe oxygen deprivation of great altitudes by an enormous increase in ventilation which has the advantage of defending the alveolar [Formula: see text] against the reduced inspired [Formula: see text]. Nevertheless the arterial [Formula: see text] on the Everest summit is less than 30 Torr (1 Torr = 133.3 Pa). An interesting consequence of the hyperventilation is that the respiratory alkalosis greatly increases the oxygen affinity of the hemoglobin and assists in oxygen loading by the pulmonary capillary. The severe hypoxemia impairs the function of many organ systems including the central nervous system, and there is evidence of residual impairment of memory and manipulative skill in climbers returning from great altitudes. At the altitude of Mt. Everest, maximal oxygen uptake is reduced to 20–25% of its sea level value, and it is exquisitely sensitive to barometric pressure. It is likely that the seasonal variation of barometric pressure affects the ability of man to reach the summit without supplementary oxygen.Key words: high altitude, hyperventilation, respiratory alkalosis, CNS impairment, barometric pressure.
Intestinal aspects of lipid absorption: in review
Authors: Thomson A. B. R. , Keelan M. , Garg M. L. , Clandinin M. T.
Published: April 2011

The rapidly evolving field of lipid absorption is reviewed with the thrust of new knowledge focused on the interpendency of the luminal and cellular phases of absorption. To date little attention has been paid to factors that regulate the phospholipid biosynthesis in the enterocyte. The availability of 20:4ω6 may be the rate-limiting factor for phospholipid synthesis. The source of 20:4ω6 is unknown, whether it be synthesized de novo the enterocyte or entirely originating from degradation of bile phospholipid. It has been established that dietary fat can modulate the enterocyte membrane lipid composition and transport properties. Specified fats such as as fish oils rich in 20:5ω3 and 22:6ω3 have been implicated as protective against hypercholesterolemia. However, the effects of these dietary fats on the transport of nutrients across the enterocyte are not yet known, nor are the mechanisms responsible for the adaptive responses of the brush border identified.