bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of nitric oxide synthase inhibitors, l‐NG‐nitroarginine and l‐NG‐nitroarginine methyl ester, on responses to vasodilators of the guinea‐pig coronary vasculature
Authors: Vials Amanda , Burnstock Geoffrey 
Published: July 2012

The effects of l‐NG‐nitroarginine (l‐NOARG) and l‐NG‐nitroarginine methyl ester (l‐NAME) on vasodilatation induced by ATP, substance P, 5‐hydroxytryptamine (5‐HT), bradykinin and sodium nitroprusside (SNP) were examined in the guinea‐pig coronary bed, by use of a Langendorff technique. The effects of these inhibitors of nitric oxide synthesis were assessed on their ability to inhibit both the amplitude and the area of the vasodilator response.
The vasodilator responses evoked by low doses of 5‐HT (5 × 10−10−5 × 10−8 mol) were almost abolished by l‐NAME and l‐NOARG (both at 10−5, 3 × 10−5 and 10−4 m), although l‐NOARG (3 × 10−5 m) was significantly less potent than l‐NAME (3 × 10−5 m) as an inhibitor of vasodilator responses to 5‐HT (5 × 10−8 mol).
The vasodilator responses evoked by substance P (5 × 10−12−5 × 10−9 mol) were reduced in the presence of l‐NAME and l‐NOARG (both at 10−5 and 3 × 10−5 m). The response to substance P was almost abolished by l‐NAME and l‐NOARG (both at 10−4 m).
The amplitude of the vasodilator responses to ATP (5 × 10−11 and 5 × 10−9−5 × 10−7 mol) was little affected by either l‐NAME or l‐NOARG (both at 10−5, 3 × 10−5 and 10−4 m). However, the area of the response to ATP (5 × 10−10‐5 × 10−7 mol) was inhibited by l‐NAME (10−5, 3 × 10−5 and 10−4 m) and to a lesser extent by l‐NOARG (10−5 and 10−4 m).
The amplitude and area of the vasodilator responses to bradykinin (5 × 10−12−5 × 10−11 mol) were reduced, but not abolished, by l‐NOARG and l‐NAME.6 Neither the amplitude nor area of the responses to sodium nitroprusside (5 × 10−10−5 × 10−7 mol) were inhibited by either l‐NAME or l‐NOARG (both at 10−5 and 3 × 10−5 m).7 It is concluded that in the guinea‐pig coronary vasculature, the vasodilatation evoked by substance P and low doses of 5‐HT is mediated almost exclusively via nitric oxide, whereas the vasodilatations evoked by ATP and bradykinin appear to involve other mechanisms in addition to the release of nitric oxide. l‐NAME was a more effective agent than l‐NOARG in inhibiting the vasodilator actions of 5‐HT and ATP in this preparation.
Endothelium‐dependent modulation of resistance vessel contraction: studies with NG‐nitro‐l‐arginine methyl ester and NG‐nitro‐l‐arginine
Authors: Bennett Michael A. , Watt Pamela A.C. , Thurston Herbert 
Published: July 2012

The effect of NG‐nitro‐l‐arginine methyl ester (l‐NAME) and NG‐nitro‐l‐arginine (l‐NOARG) on noradrenaline (NA)‐induced contractility and acetylcholine (ACh)‐induced endothelium‐dependent relaxation was studied in rat mesenteric resistance arteries.
Third order branches of mesenteric arteries were dissected and mounted on two forty micron wires in a Mulvany myograph.
Incubation with l‐NAME and l‐NOARG (10 μm) caused a time‐dependent shift in the 50% response to NA (ED50) (0.01 μm‐10 μm) but was not associated with an increase in the maximum contractile response.
l‐NAME and l‐NOARG (10 μm) caused a time‐dependent inhibition of ACh (1 μm)‐induced relaxation with a maximum effect after 120 min.
Following endothelium removal, incubation with either l‐NAME or l‐NOARG caused no significant shift in the ED50, although the residual relaxation response to ACh (1 μm) was further attenuated.6 Incubation with the cylco‐oxygenase inhibitor, indomethacin, enhanced the relaxation to ACh and reduced the inhibitory effects of l‐NAME and l‐NOARG.7 In conclusion, l‐NAME and l‐NOARG are potent inhibitors of acetylcholine‐induced endothelium‐dependent relaxation in mesenteric resistance arteries. The shift in ED50 associated wtih these inhibitors suggests a probable role for the endothelium in modulating the contractility of the resistance vasculature.
Evidence for the absence of a functional role for muscarinic M2 inhibitory receptors in cat trachea in vivo: contrast with in vitro results
Authors: Killingsworth C.R. , Yu Mingfu , Robinson N.E. 
Published: July 2012

Summary
. The effect of the selective muscarinic M2 receptor antagonist, gallamine and the selective M2 receptor agonist, pilocarpine, on airway constriction induced by vagal stimulation was studied in anaesthetized cats. In addition, the effect of gallamine on contraction of cat isolated tracheal and bronchi preparations induced by electrical field stimulation was also investigated.
. In in vivo experiments, extrathoracic airway constriction was measured with an electromechanical caliper that was attached to the outer surface of tracheal ring 4. Intrathoracic airway constriction was determined by measuring the changes in total lung resistance and dynamic compliance during vagal stimulation.
. Intravenous gallamine (0.1, 1, and 10 mg kg−1) augmented the rise in total lung resistance induced by vagal stimulation in a dose‐ and frequency‐dependent manner. At stimulation frequencies of 8 and 12 Hz the fall in dynamic compliance provoked by vagal stimulation was also significantly increased by gallamine (10 mg kg−1). Gallamine was without effect on airway constriction induced by acetylcholine.
. Vagal stimulation at 4 Hz produced significant tracheal constriction, but the amount of constriction did not change following injection of increasing doses of gallamine. Similarly, there was no difference in tracheal constriction at any frequency of stimulation (0.5–16 Hz) when frequency‐response curves before and after gallamine injection (10 mg kg−1) were compared.
. Pilocarpine (0.01–10 μg kg−1, i.v.) diminished changes in total lung resistance and dynamic compliance induced by vagal stimulation, an effect that was reversed by gallamine (10 mg kg−1, i.v.). Vagally‐induced tracheal constriction was not significantly affected by any dose of pilocarpine, nor was it modified by gallamine (10 mg kg−1) given subsequently.
. Atropine (0.5 mg kg−1) completely blocked tracheal constriction induced by vagal stimulation, indicating that the changes in tracheal ring diameter provoked by stimulation were mediated by muscarinic receptors and that intravenous drugs could reach the cervical trachealis muscle.
. In vitro tissue bath studies demonstrated a significant leftward shift of the frequency‐response curve to electrical field stimulation in both tracheal strips and bronchial rings following gallamine (10−1m) administration.
. Although the functional presence of muscarinic M2 autoreceptors was demonstrated in feline isolated tracheal and bronchial preparations, a corresponding functional role was not detected in cat trachea in vivo. This was despite repeated demonstration of muscarinic M2 receptor‐mediated limitation of airway constriction of intrathoracic airways in vivo.
Characterization of receptors involved in the direct and indirect actions of prostaglandins E and I on the guinea‐pig ileum
Authors: Lawrence Ruth A. , Jones R.L. , Wilson N.H. 
Published: July 2012

Summary
. A study of the effects of prostaglandin E2 (PGE2) and eleven synthetic analogues on the guinea‐pig isolated ileum preparation has revealed three distinct contractile actions, each associated with a different prostaglandin E (EP‐) receptor subtype. In addition, PGI2 (prostacyclin) and its stable analogues can activate prostaglandin I (IP‐) receptors to elicit both contraction and relaxation of the ileum.
. Two of the PGE actions involve direct stimulation of the smooth muscle, being unaffected by 1 μm morphine treatment. One action is blocked by AH 6809 at micromolar concentrations and ICI 80205 and 16,16‐dimethyl PGE2 are particularly potent agonists. Activation of EP1‐receptors appears to be involved. The second action is unaffected by AH 6809; sulprostone and MB 28767 are potent agonists. Comparison with agonist potency rankings on the guinea‐pig vas deferens indicates that EP3‐receptors may be involved.
. The third PGE effect and the stimulant PGI effect are blocked by morphine, indicating enteric neurones and/or sensory nerve terminals as sites of action. EP2‐receptors may be involved in the PGE action, in view of the marked effect of morphine on the contractile actions of misoprostol, 11‐deoxy PGE2‐1‐alcohol, 11‐deoxy PGE1 and butaprost, all of which show some selectivity for EP2‐receptors. The PGI action is most easily studied with cicaprost (EC25 = 1.3 nm), since iloprost, carbacyclin and to a lesser extent PGI2 also have agonist activity at EP1‐receptors.
. The contractile action of 17‐phenyl‐ω‐trinor PGE2 on the ileum is unaffected by morphine. Since this analogue shows only weak agonist activity on the rabbit jugular vein (EP2 preparation) and guinea‐pig vas deferens (EP3), it may be a more useful standard agonist than PGE2 in EP1‐receptor studies.
. In the presence of morphine and AH 6809, cicaprost inhibits histamine‐induced contractions (IC25 = 22 nm). PGI2 and iloprost show mixed inhibitory/potentiating actions, whereas carbacyclin only potentiates histamine contractions. This IP‐receptor‐mediated inhibition may account for the bell‐shaped log concentration‐response curve of cicaprost (no inhibitors present) and the very marked block of iloprost‐induced contractions by AH 6809.
. We have found no evidence for either IP‐receptors mediating direct contraction or EP‐receptors mediating inhibition of the ileum longitudinal smooth muscle, as has been suggested in the literature.
. In view of the complexity of prostanoid action on the guinea‐pig ileum we feel that the preparation must be used with caution to ascertain the EP1 agonist or antagonist potencies of novel compounds.
The effects of chronic treatment with the dihydropyridine, Bay K 8644, on hyperexcitability due to ethanol withdrawal, in vivo and in vitro
Authors: Whittington M.A. , Butterworth A.R. , Dolin S.J. , Patch T.L. , Little H.J. 
Published: July 2012

Summary
. The effects of chronic treatment with the dihydropyridine, Bay K 8644, were studied on the ethanol withdrawal syndrome, in vivo and in vitro.
. Addition of racemic Bay K 8644 to the drinking mixture, throughout the chronic ethanol treatment, decreased the behavioural excitability seen during ethanol withdrawal in vivo.
. All the signs of hyperexcitability in field potentials in the isolated hippocampal slice, caused by ethanol withdrawal, were decreased by the chronic administration of Bay K 8644.
. These effects resembled those previously reported for chronic administration of calcium channel antagonists; racemic Bay K 8644 has both calcium channel activating and antagonist properties.
. Measurement of brain levels of Bay K 8644 at the end of the chronic treatment showed that the compound reached micromolar concentrations during the treatment, but none could be detected in the tissues at the time of the above measurements.
. It is possible that the results might be explained by predominance of the calcium channel antagonist properties of this compound, owing to the high central concentrations achieved during the treatment. Tolerance to the calcium channel activating properties of Bay K 8644 may also have occurred during the chronic treatment.
Bradykinin receptors in the guinea‐pig taenia caeci are similar to proposed BK3 receptors in the guinea‐pig trachea, and are blocked by HOE 140
Authors: Field Julie L. , Hall Judith M. , Morton Ian K.M. 
Published: July 2012

Summary
. Bradykinin (BK) receptors of the guinea‐pig taenia caeci were compared with those of the guinea‐pig trachea, a preparation proposed to possess novel BK3 receptors.
. Bradykinin‐evoked contractile responses were unaffected in both preparations by the selective BK1 receptor antagonist [des‐Arg9,Leu8]‐BK (1 μm−10 μm). The BK2 receptor antagonists, d‐Arg‐[Hyp3,d‐Phe7]‐BK and d‐Arg‐[Hyp3,Thi5,8,d‐Phe7]‐BK, both had low affinities (apparent pKB estimates < 6) which did not differ significantly between the two preparations (P > 0.05). In contrast, the novel bradykinin receptor antagonist d‐Arg‐[Hyp3,Thi5,d‐Tic7,Oic8]‐BK (HOE 140) potently antagonized responses to bradykinin with relatively high affinity (apparent pKB = 8.42 ± 0.15 and 8.94 ± 0.16 in the taenia caeci, and trachea, respectively).
. We conclude that the bradykinin receptors in the guinea‐pig taenia caeci have similar recognition properties to those present in the guinea‐pig trachea, and in this respect the taenia caeci represents a useful preparation for the further study of proposed novel BK3 receptors.
Influence of NG‐nitro‐l‐arginine methyl ester on vagally induced gastric relaxation in the anaesthetized rat
Authors: Lefebvre R.A. , Hasrat J. , Gobert A. 
Published: July 2012

Summary
. The influence of the nitric oxide (NO) biosynthesis inhibitor NG‐nitro‐l‐arginine methyl ester (l‐NAME) on the gastric relaxation induced by peripheral vagal stimulation was investigated in the anaesthetized rat.
. Peripheral vagal stimulation (10 Hz, 10 V, 1 ms for 20 s) induced a reproducible biphasic response: a short‐lasting increase followed by a more pronounced decrease in intragastric pressure. This response also occurred in reserpinized animals (5 mg kg−1, i.p., 24 h before the experiment) while atropine (1 mg kg−1, i.v.) abolished the initial increase in intragastric pressure.
. l‐NAME (1–30 mg kg−1, i.v.) induced an increase in arterial blood pressure. l‐NAME (1 mg kg−1, i.v.) had no influence on the vagally induced gastric response while l‐NAME (10 and 30 mg kg−1 i.v.) significantly changed it: the initial increase in intragastric pressure was enhanced while the decrease in intragastric pressure was reduced or abolished. NG‐nitro‐l‐arginine (l‐NNA, 10 mg kg−1, i.v.) had the same effect.
. An i.v. infusion of phenylephrine (10 μg kg−1 min−1) inducing a pressor response similar to that produced by l‐NAME (30 mg kg−1, i.v.) did not influence the vagal gastric response. Infusion of l‐arginine (300 mg kg−1 bolus, then 100 mg kg−1 h−1) starting 30 min beforehand, reduced the pressor effect and prevented the influence of l‐NAME (10 mg kg−1, i.v.) on the vagal gastric response. After injection of both atropine (1 mg kg−1, i.v.) and l‐NAME (30 mg kg−1, i.v.), the vagally induced decrease in intragastric pressure was similar to that obtained under control conditions.
. These results are consistent with NO being released and inducing gastric relaxation during peripheral vagal stimulation. In addition to NO, another inhibitory non‐adrenergic non‐cholinergic neurotransmitter is released.
Effect of dihydropyridines on calcium channels in isolated smooth muscle cells from rat vena cava
Authors: Mironneau J. , Yamamoto T. , Sayet I. , Arnaudeau S. , Rakotoarisoa L. , Mironneau C. 
Published: July 2012

Summary
. Whole‐cell patch‐clamp method was applied to single smooth muscle cells freshly isolated from the rat inferior vena cava.
. Depolarizing pulses, applied from a holding potential of − 90 mV, activated both Na+ and Ca2+ channels. The fast Na+ current was inhibited by nanomolar concentrations of tetrodotoxin (TTX). The slow Ba2+ current (measured in 5 mm Ba2+ solution) was inhibited by Cd2+ and modulated by dihydropyridine derivatives. When the cells were held at a holding potential of −80 mV, racemic Bay K 8644 increased the Ba2+ current (ED50 = 10 nm) while racemic isradipine inhibited the current (IC50 = 21 nm).
. The voltage‐dependency of isradipine blockade was assessed by determining the steady‐state availability of the Ca2+ channels. From the shift of the inactivation curve in the presence of isradipine, we calculated a dissociation constant of 1.11 nm for inactivated Ca2+ channels. Scatchard plots of the specific binding of (+)‐[3H]‐isradipine obtained in intact strips incubated in 5.6 mm or 135 mm K+ solutions confirmed the voltage‐dependency of isradipine binding.
. Specific binding of (+)‐[3H]‐isradipine was completely displaced by unlabelled (±)‐isradipine, with an IC50 of 15.1 nm. This value is similar to the IC50 for inhibition of the Ba2+ current (21 nm) in cells maintained at a holding potential of −80 mV.
. Bay K 8644 had no effects on the Ba2+ current kinetics during a depolarizing test pulse. The steady‐state inactivation‐activation curves of Ba2+ current were not significantly shifted along the voltage axis.
. The present data suggest the existence of two distinct dihydropyridine binding sites which can be bound preferentially by agonist or antagonist derivatives.
Effects of cromakalim on the contraction and the membrane potential of the circular smooth muscle of guinea‐pig stomach
Authors: Ito Katsuaki , Kanno Tomohiro , Suzuki Keiko , Masuzawa‐Ito Kaoru , Takewaki Tadashi , Ohashi Hidenori , Asano Masahisa , Suzuki Hikaru 
Published: July 2012

Summary
. The effects of cromakalim on mechanical and electrical activities of the circular smooth muscles of guinea‐pig stomach antrum were observed.
. Cromakalim (> 1 × 10−7 m) decreased the amplitude of spontaneous rhythmic contractions and also the acetylcholine‐enhanced spontaneous contractions. Cromakalim was less effective against the 25.9 mm and 35.9 mm K+‐induced tonic contractions.
. Glibenclamide (1 × 10−6 m) itself caused no detectable change in the spontaneous contractions, those potentiated by acetylcholine or tonic contractions induced by high K+ solutions, but attenuated the actions of cromakalim. On the other hand, charybdotoxin (3 × 10−8 m) increased the amplitude of spontaneous contractions but failed to affect the actions of cromakalim.
. Cromakalim (> 1 × 10−6 m) decreased the amplitude and duration of slow waves, and hyperpolarized the membrane. These actions of cromakalim were completely antagonized by 1 × 10−6 m glibenclamide, whereas part of the effects of cromakalim on mechanical activity was resistant to glibenclamide.
. The results suggest that the inhibition by cromakalim of the electrical activity and the hyperpolarization, which may be associated with the opening of glibenclamide‐sensitive K+ channel, are responsible for its inhibitory action on circular smooth muscle of guinea‐pig stomach. Further, some effects independent of glibenclamide‐sensitive K+ channel may also be responsible for the mechanical effect.
Contributions of α1‐adrenoceptors, α2‐adrenoceptors and P2x‐purinoceptors to neurotransmission in several rabbit isolated blood vessels: role of neuronal uptake and autofeedback
Authors: MacDonald A. , Daly C.J. , Bulloch J.M. , McGrath J.C. 
Published: July 2012

Summary
. The roles of autofeedback and neuronal uptake in neurotransmission produced by electrical field stimulation in several rabbit isolated blood vessels were examined.
. Blocking drugs were used to separate the possible purinergic and noradrenergic contributions to the end organ response: prazosin, antagonist at postjunctional α1‐adrenoceptors; rauwolscine and yohimbine, antagonists at pre‐ and postjunctional α2‐adrenoceptors; α,β‐methylene ATP, desensitizing agent at postjunctional P2x‐purinoceptors. In addition to desensitizing postjunctional P2x‐purinoceptors, α,β‐methylene ATP potentiated the noradrenergic component of the nerve‐induced responses.
. In the presence of an intact neuronal uptake mechanism, the vessels showed different contributions of purinergic (via P2x‐purinoceptors) and noradrenergic (via α1‐adrenoceptors and α2‐adrenoceptors) components to the end organ response to nerve stimulation: saphenous artery (approximately equal contributions from P2x‐purinoceptors and α1‐adrenoceptors), ileocolic artery (mainly P2x‐purinoceptors with a smaller contribution from α1‐adrenoceptors), plantaris vein (mainly α1‐adrenoceptors with a small contribution from α2‐adrenoceptors and P2x‐purinoceptors) and saphenous vein (α1‐adrenoceptors).
. The presence of α2‐adrenoceptor‐mediated autofeedback could be demonstrated for both purinergic and noradrenergic components of the nerve‐induced responses in the artery preparations. In the veins, potentiation of nerve‐induced responses by α2‐adrenoceptor antagonists could not be studied due to blockade of postjunctional α2‐adrenoceptor‐mediated vasoconstriction.
. Blockade of neuronal uptake with cocaine potentiated the noradrenergic component of the nerve‐induced responses. Both α1‐adrenoceptor‐ and α2‐adrenoceptor‐mediated components were potentiated, with a relatively greater potentiation of the α2‐adrenoceptor‐mediated component. In the case of saphenous vein an α2‐adrenoceptor‐mediated component which was previously absent was uncovered.
. Blockade of neuronal uptake with cocaine had no effect or reduced the purinergic component of responses, the latter effect presumably due to enhanced α2‐adrenoceptor‐mediated autofeedback.
. In the presence of cocaine, nerve‐induced responses in the saphenous vein were biphasic. Rauwolscine potentiated the first phase and inhibited the second phase thus demonstrating effects of pre‐ and postjunctional α2‐adrenoceptor‐mediated activation in the same preparation.
. In conclusion, neuronal uptake and autofeedback processes play important and complex interacting parts in determining the relative contributions of α1 and α2‐adrenoceptors and P2x‐purinoceptors in the end organ response to neurotransmission in blood vessels.
Characterization of postsynaptic α‐adrenoceptors in the arteries supplying the oviduct
Authors: Costa Gonzalo , Isla Miguel , García‐Pascual Angeles , Jimenez Eugenio , Recio Paz , Labadia Alicia , García‐Sacristán Albino 
Published: July 2012

In vitro experiments were designed to characterize postjunctional α‐adrenoceptor subtypes in ring segments (1 mm length; outer diameter 300–500 μm) from arteries supplying the oviduct of the heifer.
Noradrenaline, adrenaline and phenylephrine evoked concentration‐dependent contractile responses. The pD2 values were 5.67, 5.89 and 5.93, respectively. Medetomidine, clonidine and B‐HT 920 (2‐amino‐6‐allyl‐5,6,7,8‐tetra‐hydro‐4H‐(thiazo)‐4,5‐d‐azepine) were ineffective.
The α‐adrenoceptor selective antagonists, prazosin (1 nm−0.1 μm) and rauwolscine (0.1–10 μm) competitively antagonized the response to noradrenaline. The pA2 values were 9.38 and 6.83, respectively.
The dissociation constant (KD) for noradrenaline calculated by use of the irreversible antagonist, dibenamine, was 3.95 (2.09–5.81) μm. The occupancy‐response relationship was non‐linear. Half‐maximal response to noradrenaline was obtained with 22% receptor occupancy while maximal response required 100% occupancy.
B‐HT 920 evoked a biphasic contractile concentration‐dependent response in preparations incubated in a physiological solution containing 20 mm K+, 0.1 μm prazosin and 1 μm propranolol. Rauwolscine 0.1 μm significantly (P < 0.01) blocked the first component of the B‐HT 920 concentration‐response curve with an apparent pA2 value of 8.52 (7.86–9.18).
These results strongly suggest that α‐adrenoceptors in oviductal arteries are mainly of the α1 subtype, although a possible role for α2‐adrenoceptors cannot be excluded.