bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelin‐ and neuropeptide Y‐induced vasoconstriction of human epicardial coronary arteries in vitro
Authors: Franco‐Cereceda Anders 
Published: July 2012

The effects of the recently discovered peptide endothelin and neuropeptide Y (NPY) on human epicardial coronary arteries were studied in vitro.
Endothelin induced a concentration‐dependent, endothelium‐independent, long‐lasting vasoconstriction regardless of vessel size. NPY evoked contractions of small coronary arteries with a similar potency to that of endothelin, although to a significantly lower degree. Large coronary arteries did not respond to NPY. Endothelin did not relax coronary arteries precontracted with potassium.
The effect of endothelin was dependent on extracellular Ca2+ and, like NPY, significantly reduced by the Ca2+‐antagonist nifiedipine.
In conclusion, endothelin is a potent human vasoconstrictor in vitro. It is suggested that endothelin may be involved in the regulation of coronary blood flow.
Actions of guanine nucleotides and cyclic nucleotides on calcium stores in single patch‐clamped smooth muscle cells from rabbit portal vein
Authors: Komori S. , Bolton T.B. 
Published: July 2012

Single smooth muscle cells were obtained from the rabbit portal vein by enzymic digestion and membrane currents under voltage clamp measured by whole‐cell patch clamp technique.
When held at depolarized potentials, spontaneous outward currents (STOCs) were discharged; it is likely that these represent the cyclical storage and release within the cell of calcium in relation to Ca‐activated K‐channels.
Application of lower concentrations of carbachol (10−5m) or caffeine (10−3m) accelerated STOC discharge. Higher concentrations of caffeine (10−2m) or carbachol (10−4m), or noradrenaline (10−5m), produced an outward current of 1–5 nA which disappeared within 5–15 s and which was considered to result from the discharge of calcium stores; STOC discharge was abolished for a period.
Ryanodine (10−5‐10−4m) or a non‐hydrolysable GTP analogue, GTPγS (10−5‐10−3m) introduced into the cell abolished STOC discharge within 2–5 min. STOCs were large in cells filled with GDPβS (10−3m) and the action of GTPγS introduced at various concentrations was antagonized.
GTPγS (10−4‐10−3m) in the cell reduced or abolished outward current to caffeine (10−2m) noradrenaline (10−5m) or carbachol (10−4m); the effect on caffeine outward current was antagonized by GDPβS (10−3m) introduced into the cell. GDPβS reduced noradrenaline outward current but not caffeine outward current implying the existence of a G‐protein step in noradrenaline‐evoked Ca‐store release, possibly regulating phospholipase C enzyme activity and D‐myo inositol 1,4,5 trisphosphate formation.
If cyclic AMP (10−3m) or cyclic GMP (10−3m) was introduced into the cell, or 8‐bromo cyclic AMP (0.5 × 10−3m) or 8‐bromo cyclic GMP (0.5 × 10−3m) applied to the cell in the bathing solution, STOC discharge was only slightly affected. However, the outward current to caffeine applied after noradrenaline was much enhanced.
The results could be explained if cyclic GMP and cyclic AMP enhance calcium storage whereas GTPγS depletes calcium stores, an action antagonized by GDPβS.
Effects of experimental diabetes on the responsiveness of rat aorta
Authors: Mulhern Mark , Docherty James R. 
Published: July 2012

Vascular responsiveness was examined in aortic ring preparations, with or without endothelium, from rats with experimental diabetes induced by streptozotocin and from vehicle‐treated (control) rats.
There were no significant differences between diabetic tissues and control tissues in the responsiveness to the vasoconstrictors noradrenaline, 5‐hydroxytryptamine and KCl, and to the vasodilators sodium nitroprusside, isoprenaline and acetylcholine.
When maximum contractions to vasoconstrictors was expressed relative to tissue weight, maximum contractions were significantly greater in diabetic tissues.
When expressed in terms of the KCl contraction, there were no significant differences between diabetic and control tissues in the maximum contraction to vasoconstrictors.
These results demonstrate that diabetic‐induced changes in vascular responsiveness, if any, do not occur at the receptor level.
Effects of pinacidil on the sympatho‐adrenal system in dogs
Authors: Damase‐Michel C. , Tran M.A. , Montastruc J.L. , Moatti J.P. , Montastruc P. 
Published: July 2012

The aim of the present work was to study the antihypertensive effect of pinacidil, a potassium channel opener, in sinoaortic denervated (SAD) conscious dogs and to investigate whether the involvement of the sympathetic nervous system induced by this vasodilator compound is only of baroceptor reflex origin.
Pinacidil (0.1, 0.2, 0.4 mg kg−1 i.v.) induced a dose‐dependent decrease in blood pressure in normal as well as in SAD dogs. In contrast, the induced‐tachycardia observed in normal dogs was not found in SAD animals.
Since pinacidil induced an increase in plasma catecholamines, free fatty acids, glucose, plasma renin activity and aldosterone in SAD dogs, it is suggested that this sympathetic activation is independent of the baroreceptor reflex pathways.
The sympathetic activation is mainly of peripheral origin, since pinacidil (0.7 mg kg−1 i.v.) induced an increase in adrenaline release from the adrenal gland after section of the great splanchnic nerve in anaesthetized dogs. This increase is probably due to an effect that does not involve K+ channel opening. However, this effect of pinacidil was not observed during splanchnic nerve stimulation (in this case, the involvement of K+ channel opening is suggested).
Electrophysiological abnormalities and enhanced reperfusion arrhythmias in the isolated hearts of hyperthyroid rats
Authors: Miyazawa Katsuhiko , Hashimoto Hisakuni , Uematsu Toshihiko , Nakashima Mitsuyoshi 
Published: July 2012

The influence of hyperthyroidism on electrophysiological characteristics and on reperfusion arrhythmias was examined in rat hearts.
Electrophysiological studies were performed with glass microelectrodes, and the experiments on reperfusion arrhythmias were done in isolated perfused hearts.
Ventricular muscle from hyperthyroid rats was more prone than that from euthyroid rats to develop triggered activity under conditions believed to cause myoplasmic Ca2+ overload.
The severity of reperfusion arrhythmias was significantly enhanced in hyperthyroid preparations as compared with euthyroid ones.
The enhanced reperfusion arrhythmias in hyperthyroid rats were significantly reduced by propranolol (3 × 10−7m), lignocaine (1 × 10−5m) and verapamil (3 × 10−8m), but not by nadolol (3 × 10−7m) or prazosin (3 × 10−7m).
These results suggest that increased heart rate due to hyperthyroidism and responses mediated via either α‐ or β‐adrenoceptors were not dominant causes of enhanced reperfusion arrhythmias in hyperthyroid hearts.
The increased tendency to develop triggered activity which was observed in the electrophysiological study, may be one possible explanation of enhanced reperfusion arrhythmias in hyperthyroid hearts.
Functional role of cholinoceptors and purinoceptors in human isolated atrial and ventricular heart muscle
Authors: Jakob Helga , Oelert Hellmut , Rupp Johanna , Nawrath Hermann 
Published: July 2012

The effects of cholinergic and purinergic stimulation on action potential, force of contraction and 86Rb efflux were investigated in human atrial and ventricular heart muscle.
In atrial heart muscle, carbachol and (−)‐N6‐(R‐phenyl‐isopropyl)‐adenosine (R‐PIA) and 5′‐(N‐ethyl)‐carboxamido‐adenosine (NECA) evoked transient decreases of action potential duration and force of contraction; the steady‐state effects on force of contraction were virtually identical to control values. In the presence of propranolol, steady‐state values after carbachol, R‐PIA or NECA amounted to about 50% of control values.
In ventricular heart muscle, carbachol, NECA and R‐PIA did not significantly affect the action potential configuration or force of contraction.
Carbachol, NECA and R‐PIA induced a maintained depression of the positive inotropic response to isoprenaline in both atrial and ventricular heart muscle.
The rate constant of 86Rb efflux was slightly increased by carbachol, NECA and R‐PIA in atrial (10–20%) but not in ventricular heart muscle.
In the presence of isoprenaline, carbachol, NECA and R‐PIA did not significantly affect the rate constant of 86Rb efflux in both atrial and ventricular heart muscle. Isoprenaline alone increased the rate constant of 86Rb by about 25% in both tissues.
NK‐1 receptor mediation of neurogenic plasma extravasation in rat skin
Authors: Andrews Paul V. , Helme Robert D. , Thomas Karen L. 
Published: July 2012

Plasma extravasation was induced by electrical nerve stimulation and by perfusion of tachykinins over a vacuum‐induced blister base on rat footpad.
Stimulation of the sciatic nerve (18 V, 15 Hz, 0.5 ms) for 20 min produced a significant increase in the protein content of the perfusate. The response in capsaicin pretreated rats was only 4% of the control response. This indicates that the electrically‐induced plasma extravasation response was mediated by capsaicin‐sensitive sensory fibres.
Exogenous perfusion of the mammalian tachykinins substance P, neurokinin A and neurokinin B and the non‐mammalian tachykinins physalaemin, kassinin and eledoisin was used to determine the tachykinin receptor type mediating the plasma extravasation response. Dose‐response curves of the tachykinins (10−9m−10−4m) gave a rank order of potency of substance P = physalaemin > eledoisin ≥ kassinin > neurokinin B = neurokinin A.
In addition, specific agonists of neurokinin receptors were perfused. Perfusion of [Glp6, D‐Pro9] SP6–11 and [Glp6, L‐Pro9]SP6–11 demonstrated that the L‐Pro isomer was much more potent than the D‐Pro isomer.
The rank order of potency and the greater potency of [Glp6, L‐Pro9]SP6–11 over its D‐isomer indicate an NK‐1 neurokinin receptor mediates plasma extravasation in rat footpad skin.
The binding of (+)‐isradipine by guinea‐pig intact atria
Authors: Herzig Stefan , Lüllmann Heinz 
Published: July 2012

The accumulation of [3H]‐(+)‐isradipine (PN 200‐110) was measured in quiescent guinea‐pig left atria with normal (K+ 2.7 mm) or lowered (K+ 40 mm) membrane potential.
Under control conditions (2.7 mM K+) a high affinity binding of (+)‐isradipine could not be detected. If, however, the atria were partially depolarized to about −30 mV by 40 mM K+, high affinity binding became evident displaying a dissociation constant of 4.2 × 10−11m and a capacity of 9.7 nmol kg−1 wet wt.
The depolarization‐induced binding was reversible upon repolarization of the atria although isradipine was still present in the medium. This indicates that the high affinity binding sites disappear as soon as the cell membranes become polarized.
Isradipine belongs to the less hydrophobic dihydropyridines, but nevertheless the unsaturable binding led to an accumulation of about 84 fold. At a concentration of 2 × 10−8m (+)‐isradipine, which reduces the contractile force by 50%, the cellular concentration will rise to more than 10−6m.
The mode of action of caffeine on catecholamine release from perfused adrenal glands of cat
Authors: Yamada Yutaka , Nakazato Yoshikazu , Ohga Akira 
Published: July 2012

Adrenaline and noradrenaline secretion induced by caffeine was investigated in the perfused cat adrenal glands.
Caffeine (10–80 mm) caused a dose‐dependent increase in both adrenaline and noradrenaline secretion when applied for 1 min and 10 min after replacing Ca2+ with 10−5m EGTA in the perfusion solution. The ratio of adrenaline to noradrenaline was about 1:1. Mg2+ and/or Ca2+ inhibited the response to caffeine.
When caffeine (40 mm) was repeatedly applied in the absence of extracellular Ca2+, the secretory response almost disappeared but only at the second challenge with caffeine. However, the response was partially restored after readmission of Ca2+ (2.2 mm) and was augmented after the readmission of Ca2+ with ouabain (10−5m).
Caffeine‐induced secretion of adrenaline and noradrenaline increased with the increase in the preloaded concentration of Ca2+ and attained a maximum at 16 mM Ca2+.
During perfusion with Ca2+‐free Locke solution containing hexamethonium (10−3m), acetylcholine (10−4m) caused increases in both adrenaline and noradrenaline secretions with a ratio of about 1:2. The secretory responses were partially inhibited by preceding stimulation with exposure to caffeine (80 mm).
These results suggest that caffeine mobilizes Ca2+ from an intracellular storage site that may not be entirely the same as that linked to muscarinic receptors, and causes an increase in both adrenaline and noradrenaline secretion from cat adrenal chromaffin cells.
Effect of bile acid on electrophysiological properties of rabbit sino‐atrial node in vitro
Authors: Kotake Hiroshi , Itoh Toshihiko , Watanabe Masashi , Hisatome Ichiro , Hasegawa Junichi , Mashiba Hiroto 
Published: July 2012

In order to examine the action of bile acid on cardiac pace‐maker activity, the effect of sodium taurocholate (NTC) was studied on the membrane potential and current of rabbit sino‐atrial node preparations by means of a double microelectrode voltage clamp technique.
In spontaneously beating sino‐atrial node preparations, NTC (above 30 μm) decreased the maximum rate of rise of the action potential. Above 100 μm, the compound also exerted a brady‐cardiac effect and decreased the rate of diastolic depolarization significantly.
On the current systems, NTC produced dose‐related decreases in the slow inward Ca2+ current and the time‐dependent outward K+ current.
It is concluded that NTC depresses the spontaneous discharge of the sino‐atrial node through decreases in both inward and outward current systems.
Purinoceptors in the pulmonary circulation of the rat and their role in hypoxic vasoconstriction
Authors: McCormack D.G. , Barnes P.J. , Evans T.W. 
Published: July 2012

P2‐purinoceptors have been characterized in the systemic circulation of a variety of species but little is known about their nature in the pulmonary vasculature.
In the isolated, blood perfused and ventilated lung of the rat the P2x selective analogues α,β‐methylene ATP(α,β‐meATP) (25 μg) and β,γ‐methylene ATP (400 μg) caused a rise in pulmonary artery pressure (127 ± 32% and 110 ± 23% increase respectively, n = 6), demonstrating the existence of vasoconstrictor P2 receptors in the pulmonary circulation.
Repeated boluses of α,β‐meATP resulted in complete desensitization of the constrictor response to β,γ‐meATP, but a small vasodilator response remained indicating unopposed stimulation of P2y receptors. The desensitization by α,β‐meATP had no effect on angiotensin II‐induced vasoconstriction.
After desensitization of the vasoconstrictor P2 receptors with α,β‐meATP, hypoxic pulmonary vasoconstriction remained intact, indicating that these receptors are not involved in this response.
Caffeine‐induced inhibition of calcium channel current in cultured smooth muscle cells from pregnant rat myometrium
Authors: Martin C. , Dacquet C. , Mironneau C. , Mironneau J. 
Published: July 2012

The inhibitory effect of caffeine on the calcium channel current was investigated in cultured myometrial cells isolated from pregnant rats.
Caffeine inhibited the calcium channel current elicited from a holding potential of — 70 mV in a concentration‐dependent manner. The IC50 was estimated to be 35 mM.
The caffeine inhibition was not enhanced when calcium channels were opened by a conditioning depolarizing pulse sequence or when the number of inactivated calcium channels was increased at depolarized holding potentials.
Caffeine antagonized the specific binding of (+)‐[3H]‐isradipine to myometrial membranes. The IC50 value found in binding experiments was similar to the IC50 value for half‐maximal inhibition of calcium channel current. Caffeine decreased the maximal binding capacity of (+)‐[3H]‐isradipine to myometrial membranes without any significant change in the dissociation constant.
The results indicate that caffeine interacts with a site closely associated with the voltage‐dependent calcium channels in myometrial cells and, in turn, inhibits calcium influx.
Modulation of neurotransmission in the guinea‐pig vas deferens by capsaicin: involvement of calcitonin gene‐related peptide and substance P
Authors: Ellis James L. , Burnstock Geoffrey 
Published: July 2012

The effects of capsaicin, calcitonin gene‐related peptide and substance P were studied via three parameters in the guinea‐pig vas deferens: the overflow of ATP and of tritiated noradrenaline, the mechanical responses to field stimulation and the mechanical responses to exogenous noradrenaline and α,β‐methylene ATP.
At 2 Hz, capsaicin inhibited the stimulus‐evoked release of ATP, whereas it was without effect on the release of noradrenaline. At 20 Hz capsaicin did not affect the release of either of the co‐transmitters. Capsaicin enhanced responses to α,β‐methylene ATP, but not to exogenous noradrenaline.
Calcitonin gene‐related peptide, like capsaicin, inhibited the release of ATP, but not noradrenaline at 2 Hz and was without effect on release at 20 Hz. However, calcitonin gene‐related peptide inhibited responses to α,β‐methylene ATP and was without effect on responses to exogenous noradrenaline.
Substance P had no effect on the release of either noradrenaline or ATP at either frequency. However, like capsaicin it enhanced responses to α,β‐methylene ATP and was without effect on exogenous noradrenaline.
These results suggest that the actions of capsaicin on the guinea‐pig isolated vas deferens are mediated via the release of both calcitonin gene‐related peptide and substance P. Furthermore, as capsaicin and calcitonin gene‐related peptide prejunctionally modulate purinergic, but not noradrenergic transmission, this suggests that the mechanisms for the storage and release of the sympathetic co‐transmitters noradrenaline and ATP may not be the same.
Increase in gastric secretion induced by 2‐deoxy‐D‐glucose is impaired in capsaicin pretreated rats
Authors: Evangelista S. , Santicioli P. , Maggi C.A. , Meli A. 
Published: July 2012

Gastric acid secretion was determined following intravenous administration of 2‐deoxy‐D‐glucose (2‐DG; 60 mg kg−1) or electrical stimulation of the vagus nerve in urethane‐anaesthetized rats pretreated when newborn with either capsaicin or the vehicle. The secretory response to 2‐DG was substantially reduced in the capsaicin pretreated rats, while that induced by electrical vagal stimulation (1 mA, 1 ms, 3 Hz) was unaffected.These results suggest that capsaicin‐sensitive fibres are involved in the afferent branch of the reflex response activated by 2‐DG to stimulate gastric acid secretion.
Ventricular fibrillation is reduced in hypothyroid rats with enhanced myocardial α‐adrenoceptor responsiveness
Authors: Chess‐Williams R. , Coker S.J. 
Published: July 2012

The severity of ventricular arrhythmias induced by coronary artery occlusion and reperfusion has been examined in control rats and animals made hypothyroid by pretreatment with 6‐propylthiouracil (PTU). The maximal driving frequency and sensitivity of isolated left atria and papillary muscles to isoprenaline and to phenylephrine in the presence of propranolol, were also examined in tissues from control and hypothyroid animals.
Pretreatment with PTU resulted in a potentiation of responses to the α‐adrenoceptor agonist phenylephrine in both left atria and papillary muscles, while responses to isoprenaline were depressed in left atria but unaltered in papillary muscles from hypothyroid animals.
In rats subject to coronary artery occlusion, PTU pretreatment reduced the incidence of ventricular fibrillation during acute myocardial ischaemia and abolished reperfusion‐induced ventricular fibrillation. Mortality during myocardial ischaemia and reperfusion was also abolished. Diastolic blood pressure was similar in hypothyroid and control animals, but there was a small reduction in systolic blood pressure and a marked decrease in heart rate in PTU pretreated animals.
These results demonstrate that PTU‐induced hypothyroidism represents a condition where cardiac α‐adrenoceptor‐mediated responses are enhanced but the severity of ischaemia‐ and reperfusion‐induced arrhythmias is reduced.
Restricted usefulness of tetraethylammonium and 4‐aminopyridine for the characterization of receptor‐operated K+ ‐channels
Authors: Drukarch B. , Kits K.S. , Leysen J.E. , Schepens E. , Stoof J.C. 
Published: July 2012

Recently, we suggested that the D2‐dopamine receptor involved in the inhibition of evoked [3H]‐acetylcholine release from rat striatum is coupled to K+‐channels.
In the present study, an attempt was made to elucidate further the role of these K+‐channels, using the K+‐channel blocking agents tetraethylammonium and 4‐aminopyridine. With a superfusion method, the effects of both drugs on the D2‐dopamine receptor‐mediated inhibition of the electrically evoked release of [3H]‐acetylcholine from rat striatal tissue slices was investigated.
Both tetraethylammonium (30 mM) and 4‐aminopyridine (0.1 mM) significantly stimulated the electrically evoked release of [3H]‐acetylcholine and completely abolished the effect of the selective D2‐receptor agonist LY 171555 (1 μm) on evoked acetylcholine release. In addition, tetraethylammonium (0.03–30 mM) and 4‐aminopyridine (0.003‐1 mM) strongly increased the basal (non‐evoked) release of radioactivity in a concentration‐dependent manner. The results suggest that the effect of the drugs on the basal release of radioactivity and on the electrically evoked release of acetylcholine cannot exclusively be explained by their action on K+‐channels.
Furthermore, with the use of a receptor binding assay, data were obtained on the affinity of tetraethylammonium and 4‐aminopyridine for D2‐receptors and various other neurotransmitter recognition sites. At concentrations in which both drugs are known to block K+‐channels, they were found to inhibit the specific binding of selective radioligands to their respective recognition sites.
It is concluded that due to their ‘side‐effects’, both tetraethylammonium and 4‐aminopyridine are of only limited value in the investigation of the alleged interaction between neurotransmitter receptors and K+‐channels.
Endothelin induces an increase in renal vascular resistance and a fall in glomerular filtration rate in the rabbit isolated perfused kidney
Authors: Cairns Hugh S. , Rogerson Mary E. , Fairbanks Lynette D. , Neild Guy H. , Westwick John 
Published: July 2012

The effects of endothelin infusion on renal vascular resistance (RVR), glomerular filtration rate (GFR) and the interaction with locally generated endothelium‐derived relaxant factor (EDRF) were studied in the rabbit isolated perfused kidney (IPK). For comparison the effects of infusions of angiotensin II (AII) and noradrenaline (NA) were also assessed.
Each kidney was perfused at a constant rate of 10 ml min−1 and alterations in RVR determined by measuring changes in perfusion pressure. GFR was determined by the clearance of [51Cr]‐EDTA, using timed urine collections.
Endothelin (10−11‐10−9 M) produced a dose‐related increase in RVR. Endothelin was approximately 30 times more potent in molar terms than AII and 500 times more than NA at inducing a 50 mmHg increase in perfusion pressure.
Endothelin appeared to be a weak inducer of EDRF release in the IPK as EDRF inhibitors methylene blue (10 μm) or haemoglobin (10 μm) only slightly augmented the increase in RVR at a given concentration of endothelin. In contrast the effect of NA on RVR was significantly increased by methylene blue (10 μm) whereas that induced by AII was not affected.
Endothelin infusion produced a significant, dose‐dependent decrease in GFR of the IPK, contrasting with an increase in GFR during AII infusion and a minimal effect of NA on GFR. This supports evidence that AII is predominantly a constrictor of efferent glomerular arterioles and that NA constricts both afferent and efferent glomerular vessels. We suggest that the vasoconstrictive effect of endothelin in the kidney is predominantly preglomerular, which explains its effect on GFR.