bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of the dihydropyridine Bay K 8644 in guinea‐pig isolated trachealis
Authors: Allen S.L. , Foster R.W. , Small R.C. , Towart R. 
Published: July 2012

In trachea bathed by Krebs solution containing indomethacin 0.8 μmol 1−1, Bay K 8644 (0.01‐1 μmol 1−1) evoked mild spasm. Peak tension was achieved after 10 min and was generally less than 20% of an acetylcholine (ACh) maximum. The effect of Bay K 8644 was not potentiated by addition of 2.5 mmol 1−1 potassium chloride (KCl) to the Krebs solution.
Bay K 8644 (1 μmol 1−1) caused a small potentiation of KCl and tetraethylammonium (TEA). In contrast it did not modify the actions of ACh or histamine.
Bay K 8644 (1 μmol 1−1) caused a small potentiation of the effect of calcium chloride (CaCl2) tested in trachea bathed by a K+‐rich, Ca2+‐free, MOPS‐buffered physiological salt solution.
Organic inhibitors of calcium influx such as nifedipine (0.1 μmol 1−1), verapamil (1 μmol 1−1) or diltiazem (10 μmol 1−1) each caused marked depression of concentration‐effect curves to KCl. Bay K 8644 (0.01‐1 μmol 1−1) provided concentration‐dependent protection against this effect in all three cases.
Estimation of calcium influx by the lanthanum technique revealed that Bay K 8644 (1 μmol 1−1) was able to promote the cellular influx of Ca2+.
Intracellular electrophysiological recording showed that Bay K8644 (1 μmol 1−1) caused no change in the resting membrane potential of trachealis cells and no change in the properties of the spontaneous electrical slow waves. However, Bay K 8644 was able to delay the slow wave suppression evoked by 1 μmol 1−1 nifedipine.
The ability of Bay K 8644 to promote Ca2+ influx and its ability to protect against the effects of several structurally‐unrelated inhibitors of Ca2+ influx are consistent with Bay K 8644 acting as an agonist at the dihydropyridine receptor associated with the voltage‐operated Ca2+ channel (VOC) of trachealis muscle. By this action it potentiates those spasmogens (KCl, TEA) which act by permitting Ca2+ influx through VOCs. In contrast it has no effect on those spasmogens (ACh, histamine) which principally act to liberate Ca2+ from intracellular sites of sequestration.
Potassium changes the relationship between receptor occupancy and the inotropic effect of cardiac glycosides in guinea‐pig myocardium
Authors: Bachmaier A. , Ebner F. , Reiter M. 
Published: July 2012

K+ (2.4–15.6 mmol l−1) antagonized the positive inotropic effect of dihydro‐ouabain. The concentration‐effect curves became steeper with the shift to higher concentrations of the glycoside. At 1.2 mmol l−1 Ca2+, an increase in K+ from 2.4 to 12 mmol l−1 required tenfold higher concentrations of dihydro‐ouabain to produce equal inotropic effects. This factor was reduced to four at 3.2 mmol l−1 Ca2+. The same change in K+ concentration, at 1.2 mmol l−1 Ca2+, diminished the inotropic effect of ouabain on rested‐state contractions by a factor of six.
The positive inotropic effect of Ca2+ was also antagonized by K+ (1.2–12 mmol l−1). Reduction of Na+ from 140 to 70 mmol l−1 abolished the antagonistic action of K+ (1.2–8.0 mmol l−1) Moreover the inotropic effect of Ca2+ was enhanced.
Reduction of Na+, from 140 to 70 mmol l−1, antagonized the positive inotropic effect of dihydro‐ouabain more at low (2.4 mmol l−1) than at high (8.0 mmol l−1) K+. Accordingly, the extent of the dihydro‐ouabain‐K+ antagonism was reduced.
When the K+ concentration was increased from 2.4 to 12 mmol l−1, [3H]‐ouabain binding was reduced by a factor of three. This is less than the reduction in the inotropic effectiveness of ouabain or dihydro‐ouabain.
Reduction of stimulation frequency from 1 to 0.1215 Hz did not significantly alter the antagonistic effect of K+. Diminution of of the action potential was observed only at K+ concentrations greater than 5.9 mmol 1−1, whereas the resting membrane potential was continuously depolarized over the entire range of K+ concentrations.
The results support the view that the reduction in receptor affinity cannot be the sole cause of the antagonism between the glycoside and K+. Impairment of passive Na+ influx during diastole, due to the K+‐dependent depolarization of the resting membrane potential, contributed to about one half of the glycoside‐K+ antagonism.
The effect of hypoxia on neuroeffector transmission in the bovine retractor penis and rat anococcygeus muscles
Authors: Bowman Anne , McGrath J.C. 
Published: July 2012

The effects of reducing the Po2 of the bathing fluid were studiedon non‐adrenergic non‐cholinergic (NANC) transmission in isolated preparations of the bovine retractor penis muscle, the rat anococcygeus muscle, the guinea‐pig taenia caeci and the guinea‐pig urinary bladder.
Hypoxia rapidly and reversibly impaired NANC transmission in the bovine retractor penis and rat anococcygeus muscles but did not affect transmission in the guinea‐pig taenia caeci or bladder, suggesting that different NANC mechanisms are involved.
Although neurally‐evoked relaxation of the bovine retractor penis was impaired by hypoxia, relaxations produced by vasoactive intestinal peptide, prostaglandin E1, sodium nitroprusside or an inhibitory factor isolated from the bovine retractor penis were unaffected. Since the inhibitory factor is similar to, and may actually be the NANC transmitter, the results suggest that the site of action of hypoxia in impairing transmission is prejunctional at the inhibitory nerve endings.
An unusual effect of γ‐aminobutyric acid on synaptic transmission of frog tectal neurones in vitro
Authors: Nistri A. , Sivilotti Lucia 
Published: July 2012

Bath‐applied γ‐aminobutyric acid (GABA) enhanced, in a dose‐dependent fashion, the amplitude of optic nerve‐evoked monosynaptic excitatory responses of the frog optic tectum superfused in vitro at 7°C.
Muscimol was more potent than GABA in eliciting similar effects.
GABA‐induced responses were antagonized by picrotoxin and were insensitive to bicuculline or strychnine.
Raising the bath temperature to 20°C reduced the potency of GABA on these preparations.
No significant effect of GABA on the compound action potential of the whole optic nerve was found.
These data indicate that GABA can amplify visual inputs to the tectum through bicuculline‐insensitive mechanisms.
Evidence that oxmetidine inhibits transmembrane calcium flux in cardiac and vascular tissue
Authors: Gristwood R.W. , Jim K.F. , Macia R.A. , Matthews W.D. , Morl C.J. , Owen D.A.A. 
Published: July 2012

Oxmetidine, at concentrations in excess of 1 times 10−6M, caused concentration‐dependent negative inotropic and chronotropic responses in guinea‐pig isolated heart preparations.
Oxmetidine, at concentrations in excess of 1 times 10−5M, caused negative inotropic responses in guinea‐pig papillary muscle preparations. The negative inotropic responses to oxmetidine were associated with shortening of the plateau phase of the action potential.
Verapamil and nifedipine caused similar shortening of the plateau phase of the action potential at equivalent negative inotropic concentrations indicating that oxmetidine may also act as a calcium antagonist.
In preparations partially depolarized by raising extracellular K+ concentration, oxmetidine also exhibited negative inotropic activity and reduced the calcium‐dependent action potential. However, unlike verapamil and nifedipine, oxmetidine did not show voltage‐dependent activity.
Oxmetidine, at concentrations in excess of 1 times 10−5M, inhibited Ca2+‐dependent contractions of dog saphenous vein preparations and inhibited 45Ca2+‐uptake into veins depolarized by high extracellular K+.
In vivo, these calcium antagonist actions of oxmetidine were demonstrated by vasodilatation, reduction in blood pressure, bradycardia and reduced cardiac output in anaesthetized cats.
Oxmetidine, at concentrations of 1 times 10−5M and above, shows properties consistent with inhibition of transmembrane Ca2+ flux. This action can be distinguished from other calcium antagonists as the effects of oxmetidine are not voltage‐dependent.
Acceleration of recovery of gastric epithelial integrity by 16,16‐dimethyl prostaglandin E2
Authors: Wallace John L. , Whittle Brendan J.R. 
Published: July 2012

The effects of pretreatment with 16,16‐dimethyl prostaglandin E2 (DmPGE2) on the recovery of gastric mucosal ‘barrier’ parameters after ethanol‐induced damage were studied using an ex vivo chamber preparation in the rat.
DmPGE2 (4–40 μg kg−1) significantly reduced the extent of haemorrhagic damage to the gastric mucosa induced by the topical application of 50% ethanol followed by 0.05 M hydrochloric acid.
The lowest dose of DmPGE2 tested (4 μg kg−1) had no effect on the ethanol‐induced changes in transmucosal potential difference (PD) or K+ efflux. However, DmPGE2 at doses at 20 or 40 μg kg−1 significantly reduced the changes in these indices of epithelial integrity.
The recovery of PD and K+ efflux to control levels after ethanol‐injury was accelerated by DmPGE2.
With the two higher doses of DmPGE2 (20 and 40 μg kg−1) there was a significantly (P < 0.001) lower level of epithelial discontinuity, measured histologically, in samples taken at the end of the experiment.
These results suggest that at the higher doses, DmPGE2 confers some protection to the gastric epithelium as well as accelerating the recovery of epithelial integrity after damage induced by ethanol.
Dietary and pharmacological alterations in endogenous angiotensin II: effect on noradrenaline pressor responsiveness in the rat
Authors: Jones Donald R. , Penner S. Brian , Smyth Donald D. 
Published: July 2012

Rats were placed on either a low sodium intake (low sodium diet 0.025% dry weight, tap water for drinking) or a high sodium intake (normal sodium diet 0.45% dry weight, 0.9% saline for drinking) for 10 days. The pressor‐response curve to angiotensin II in rats previously on a high sodium intake was shifted to the left of that found in rats previously on a low sodium intake.
Suppression of endogenous angiotensin II formation with captopril (0.3 mg kg−1) or acute volume repletion (3% body wt per 30 min) resulted in a significant parallel shift of the pressor‐response curve for angiotensin II to the left in the low salt group. In the high salt group captopril produced a similar but smaller parallel shift of the dose‐response curve to the left.
Similar manipulation of endogenous angiotensin II concentrations with high and low salt intake plus captopril treatment or acute volume repletion, produced no alterations in the pressor response for noradrenaline.
The attenuated in vivo response to angiotensin II in the low salt intake group may be explained in part by the suppressed vascular sensitivity to angiotensin II in this group, as measured in the isolated perfused kidney of the rat. In kidneys from rats previously on a low sodium intake, an enhanced maximal vasoconstrictor response to noradrenaline was observed as compared to kidneys from high sodium intake rats.
These results indicate that, whereas alterations in endogenous angiotensin II concentrations within physiological limits affects the response to exogenous angiotensin, there is little if any effect on the pressor response to noradrenaline.
The effects of nisoldipine (Bay K 5552) on cardiovascular performance and regional blood flow in pentobarbital ‐ anaesthetized pigs with or without β‐adrenoceptor blockade
Authors: Duncker D.J. , Hartog J.M. , Hugenholtz P.G. , Saxena P.R. , Verdouw P.D. 
Published: July 2012

The effects of the 1,4‐dihydropyridine derivative nisoldipine, infused intravenously (i.v.) at 3 different rates (0.25, 0.5 and 1.0 μg kg−1 min−1), were studied in anaesthetized pigs on cardiovascular performance with or without β‐adrenoceptor blockade produced by propranolol.
Nisoldipine caused dose‐dependent decreases in arterial blood pressure (30%), systemic vascular resistance (30%) and left ventricular filling pressure (15%), but raised heart rate (25%) and LV dP/dt max (20%). Cardiac output was not significantly affected.
Transmural myocardial blood flow and vascular conductances increased dose‐dependently after nisoldipine. The elevation in blood flow to the left ventricle favoured epicardial layers. Endocardial blood flow showed small increases as the changes in conductance of the endocardial layer more than compensated for the loss in perfusion pressure. The endo‐epi blood flow ratio decreased from 1.16 ± 0.05 to 0.70 ±0.01. Myocardial O2‐consumption was unaltered as the decrease in arterial‐coronary venous O2‐content difference (30%) was balanced by the increase in transmural blood flow.
Nisoldipine increased blood flow to skeletal muscle (500%), stomach (50%) and adrenals (25%), but decreased that to the liver (50%), spleen (25%) and kidneys (25%). No changes were noticed in the small intestine, skin and brain. In spite of differential effects on blood flow, vascular conductance in all organs and tissues, with the exception of the liver, increased.
After β‐adrenoceptor blockade the responses of mean arterial blood pressure, cardiac output and systemic vascular resistance to nisoldipine remained virtually unchanged, but the elevations in heart rate and LV dP/dt max were abolished, as was the decrease in left ventricular filling pressure.
A higher dose of nisoldipine was required after β‐adrenoceptor blockade to elicit significant vasodilatation in the epi‐ and endocardial layers. However, the reduction in endo‐epi blood flow ratio by nisoldipine was not affected by propranolol. Myocardial O2‐consumption tended to decrease as the diminution in the arterial‐coronary venous O2‐content difference (30%) slightly exceeded the increase of left ventricular blood flow (30%).
Except for the brain and liver, effects of nisoldipine on regional vascular conductances were attenuated after β‐adrenoceptor blockade.
Propylbenzilylcholine mustard is selective for rat heart muscarinic receptors having a low affinity for agonists
Authors: Christophe Jean , De Neef Philippe , Robberecht Patrick , Waelbroeck Magali 
Published: July 2012

Propylbenzilylcholine mustard (PrBCM), an irreversible muscarinic antagonist, inactivated receptors with a low affinity for agonists faster than those with a high affinity in rat heart membranes. This result was obtained using either: (a) a low ionic strength buffer (allowing heterogeneity among antagonist binding sites, (b) the same buffer enriched with GTP, or (c) a high ionic strength buffer (where antagonists showed similar binding characteristics to all receptors).
These data suggest either that PrBCM is a ‘selective’ antagonist which detects conformational differences between low and high affinity receptors, or that the agonist affinity of cardiac muscarinic receptors is determined, in part, by the relative concentrations of receptor and GTP binding protein.
Pharmacokinetics and antiarrhythmic activity of ajmaline in rats subjected to coronary artery occlusion
Authors: Hashimoto Yukiya , Hori Ryohei , Okumura Katsuhiko , Yasuhara Masato 
Published: July 2012

The pharmacokinetics and the antiarrhythmic action of intravenous ajmaline were investigated in anaesthetized rats subjected to coronary artery occlusion.
Ajmaline (0.125‐2 mg kg−1, i.v. given just after occlusion) suppressed arrhythmias in a dose‐dependent manner, judged by the reduction of premature ventricular complexes. The incidence of malignant arrhythmias (ventricular tachycardia and fibrillation) was preferentially suppressed at the higher doses of ajmaline (1 and 2 mg kg−1).
Coronary occlusion induced a change in pharmacokinetics of ajmaline (2 mg kg−1) and its total body blood clearance was significantly decreased from 56.6 ml min−1 kg−1 in sham‐operated rats to 43.1 ml min−1 kg−1 in rats after coronary occlusion.
Ajmaline exhibited a significantly increased negative dromotropic action (increased PQ interval) in rats after coronary occlusion compared with that in sham‐operated rats. The difference seems to be due to the pharmacokinetic change since the concentration‐effect relationship was similar in the two groups of rats.
We suggest that the measurement of drug levels is important in the assessment of antiarrhythmic agents.
How is ventilation maintained in the presence of the muscle relaxant, dantrolene sodium? A study in the anaesthetized rat
Authors: Farquhar Ruth , Leslie G.C. , Part N.J. 
Published: July 2012

The effects of intravenous injection of the muscle relaxant dantrolene sodium on ventilation, integrated EMG of external intercostal muscles and motor unit discharge in these muscles were measured in anaesthetized rats.
Dantrolene sodium was administered in a carrier solution at pH 10. The carrier was not responsible for the effects seen on dantrolene sodium infusion.
Dantrolene sodium (5 mg kg−1 body weight) reduced inspired ventilation (V̇1) on average from 308 ± 106 ml min−1 (s.d., n = 8) in the control period to 247 ± 118 ml min−1 (n = 8) after dantrolene sodium. Expired ventilation was reduced likewise from 214 ± 132 ml min−1 (n = 8) to 229 ± 109 ml min−1 (n = 8). These changes are significant at P < 0.05.
The integrated EMG was increased by 40.0 ± 29.3% (n = 9), a change significant at P < 0.001.
Dantrolene sodium not only decreased the mean interspike interval of individual motor units by 16.2 ± 11.1 % (n = 13), a change significant at P < 0.001, but also increased the duration of the burst of activity of each individual motor unit on average by 36.2 ± 52.4% (n = 13), a change significant at P < 0.05.
The recruitment of additional motor units was also effected by dantrolene sodium. These units did not behave in any noticeably different manner from units previously active.
It is concluded that the nervous system compensates for the effect of dantrolene sodium only to a limited extent by increasing the frequency of discharge of active motor units. Recruitment of additional motor units and increased burst duration play at least as important a role.
Action of dopamine on the exocrine pancreatic secretion of the intact dog
Authors: Delcenserie R. , Devaux M.A. , Sarles H. 
Published: July 2012

The effects of dopamine and domperidone, a dopamine antagonist, have been studied on the exocrine secretion of the dog pancreas. The purpose of this study was to see if dopamine acted on enzyme secretion and if its action was merely ‘pharmacological’ or had a physiological role.
Conscious Beagle dogs, fitted with Thomas cannulae were studied following infusions of dopamine 125–1000 μg kg−1 h−1.
During dopamine infusion, a secretory peak lasting 10 min was observed. This was followed by a stable plateau which was approximately 1/3 of the peak. The pattern of water, bicarbonate and protein secretion was similar. The maximum effect was obtained with 500 μg kg−1 h−1 dopamine.
The stimulatory action of dopamine was blocked by domperidone, without any detected effect on the central nervous system, but not by propranolol or phenoxybenzamine. Domperidone 10 μg kg−1 almost completely suppressed the secretory response to the maximally effective dose of dopamine. This inhibition was not competitive. Atropine decreased the secretory response to dopamine.
The protein response was not observed when dopamine was infused against a background infusion of secretin. This suggests that the effect of dopamine on protein secretion could be due to a wash‐out phenomenon.
The maximally effective dose of domperidone, 10 μg kg−1, did not modify the pancreatic response to a solid meal.
Thus, in the non‐anaesthetized dog, the effect of dopamine on water and bicarbonate secretion has been confirmed. It is concluded that dopamine had no detectable action on protein secretion and that the physiological role of dopamine with respect to pancreatic secretion is still questionable.
Hypersensitivity to methoxamine in atria isolated from streptozotocin‐induced diabetic rats
Authors: Canga Liliana , Sterin‐Borda Leonor 
Published: July 2012

The reactivity to methoxamine (Met) of atria isolated from the hearts of normal and from acutely streptozotocin‐diabetic rats has been studied.
Met (1 × 10−6 M) increased the tension of both normal and diabetic atria, but in diabetic atria, the dose‐response curve to Met was shifted to the left and the efficacy of Met was enhanced.
Inhibitors of α‐adrenoceptors blocked, in a competitive manner, the positive inotropic effect induced by Met in both types of atrial preparations.
Inhibitors of the cyclo‐oxygenase pathway for arachidonic acid metabolism blocked the atrial response to Met in non‐diabetic as well as in diabetic atria. The inhibition of prostacyclin synthetase prevented the effect of Met in normal atria, while blockers of thromboxane generation inhibited it in diabetic ones.
Agents that inhibit the activity of lipoxygenase(s) significantly reduced the positive inotropic action induced by Met in diabetic atria but failed to modify it in non‐diabetic preparations.
These results show that diabetic atria are more sensitive to Met than normal atria. In diabetes the response to α‐adrenoceptor stimulation could be mediated by oxidative products generated via thromboxane synthetase and lipoxygenase(s) activities; whereas in normal preparations the action of Met may involve the release of prostacyclin.
Non involvement of γ‐aminobutyric acid in catechol‐induced seizures
Authors: Dewhurst D.G. 
Published: July 2012

The effects of certain anticonvulsant agents, namely, vaproate, diazepam and phenobarbitone were investigated on catechol‐induced spontaneous and evoked convulsions, in anaesthetized rats and mice.
Valproate and diazepam significantly reduced the intensity of spontaneous convulsions and the frequency of occurrence of the longer‐latency components (M2 and M3) of the evoked muscle response.
Phenobarbitone significantly reduced spontaneous convulsions and the M3 component of the evoked muscle response.
None of the drugs affected the short latency M1 component indicating a supra‐spinal site of action of these drugs.
Agents which modify γ‐aminobutyric acid (GABA)‐mediated transmission were without effect on the frequency of occurrence of M1, M2 or M3.
The results suggest that the convulsant action of catechol is not dependent on antagonism of GABA‐mediated inhibition.