Effect of bombesin and substance P on the smooth muscle of the chicken crop

The effect of bombesin and of substance P was investigated in smooth muscle strips of the chicken crop. Bombesin in picomolar concentration (0.1×10^-12–5×10^-12mol/l) caused a concentration-related contraction of the muscle strips. Substance P in nanomolar concentration (0.1×10^-9–10×10^-9mol/l) was effective in the same manner. Tetrodotoxin (2×10^-7mol/l) did not influence the contraction responses to either bombesin or substance P. The excitatory effect of bombesin and of substance P did not follow activation of cholinergic receptors since their effect on the crop smooth muscle was not antagonized by atropine (10^-4mol/l) or by hexamethonium (10^-4mol/l). Strips stored for 24 hours in the Tyrode's solution at 4°C without a supply of oxygen maintained their full sensitivity to bombesin and to substance P. These results are consistent with a direct action of bombesin and substance P on the crop smooth muscle.     

5-Hydroxytryptamine potentiates contraction mediated by the intramural cholinergic nerve in the longitudinal smooth muscle of the ruminant forestomach

The effects of 5-hydroxytryptamine (5-HT) on the longitudinal smooth muscle from the rumen and reticulum of the bovine forestomach were investigated. 5-HT (0.25–490 μM) caused a contraction and a relaxation of the ruminal strips while it produced only an excitatory effect on the reticular strips. These effects were not affected by tetrodotoxin, hexamethonium, atropine or morphine, but were blocked by methysergide, LSD-25 or phenoxybenzamine. 5-HT potentiated the contraction evoked by stimulation of the intramural cholinergic nerves but did not show any effect on the relaxation produced by the non-adrenergic inhibitory nerves' excitation. The 5-HT-induced potentiation was not affected by morphine, LSD-25, methysergide and hexamethonium or high concentration of nicotine. Nicotine and dimethylphenylpiperazinium also caused a transient augmentation of the nerve-mediated contraction, but these effects were abolished by the competitive ganglionic blockers. The evoked contraction was depressed in high-Mg²⁺ solution, but this depression was antagonized partly by 5-HT. The affinity of the cholinomimetics to post-synaptic muscarinic receptor was not affected by 5-HT. It is concluded that contractions or relaxations of bovine forestomach strips induced by 5-HT are mediated through activation of D-receptors in the smooth muscle, and the 5-HT-induced potentiation of the evoked contraction may be elicited through presynaptic neural effects of 5-HT on the cholinergic nerves.     

Histamine receptors mediate contraction of reticular groove smooth muscle of adult goats

The present study was conducted to evaluate the effect of histamine and to characterise its receptor subtypes in reticular groove (RG) smooth muscle of adult goats. The studies were done using floor and lip regions of RG. We used tension experiments on smooth muscle of RG isolated from adult goat for functional characterisation of H₁ and H₂ receptors. Western blotting and immunohistochemistry experiments were conducted for molecular characterisation of these receptors. Histamine evoked concentration-dependent contraction of isolated RG circular and longitudinal smooth muscle preparation. Pyrilamine antagonised the action of histamine. Histamine did not induce any relaxant effect on RG preparations. Additionally, cimetidine did not produce any significant effect on histamine-induced response. Non-selective histaminic receptor antagonist cyproheptadine attenuated the contraction response to histamine in the smooth muscle. Molecular characterisation and localisation of H₁ and H₂ receptor proteins confirmed the presence of these receptors in RG. It is most likely that histamine-induced contractile effect in RG smooth muscle of goats is mediated by H₁ histaminic receptors.     

Spasmogenic action of endothelin-1 on isolated equine pulmonary artery and bronchus

REASONS FOR PERFORMING STUDY: There is currently little published information about the effects of endothelin-1 (ET-1), a potent endogenous spasmogen of vascular and airway smooth muscle, on pulmonary vasculature and airways or which ET receptor subtypes mediate ET-1-induced vasoconstrictive and bronchoconstrictive action in the horse. OBJECTIVES: To investigate the effect of endothelin-1 (ET-1) on smooth muscle from isolated equine pulmonary artery and bronchus. In addition, the roles of ETA and ETB receptors in ET-1 mediated contraction in these tissues were assessed. METHODS: The force generation of ring segments from pulmonary arteries or third-generation airways (obtained from horses subjected to euthanasia for orthopaedic reasons) were studied in an organ bath at 37 degrees C in response to exogenous endothelin and selective endothelin A (BQ123) or B receptor (BQ788) antagonists. RESULTS: ET-1 produced concentration-dependent contractions of the equine pulmonary artery and bronchus. The threshold for contraction was 10(-10) and 10(-9) mol/l ET-1 for pulmonary artery and bronchus, respectively. The maximal contraction induced by the highest ET-1 concentration (10(-7) mol/l) was 173 and 194% of the contraction obtained with 100 mmol/l KCl in pulmonary artery and bronchus, respectively. ET-1 potency was 25 times greater in equine pulmonary artery than in equine bronchus (concentration of ET-1 producing 50% of maximal contraction [EC50] = 5.6 10(-9) mol/l and 2.2 10(-8) mol/l, respectively). In pulmonary artery, ET-1 induced contractions were significantly inhibited by the ETA receptor antagonist BQ123 (1 micromol/l; dose-response curve to ET-1 was shifted to the right by 5.4-fold), but not by the ETB antagonist BQ788. In bronchus, dose-responses curves to ET-1 were shifted to the right by BQ123 (1 micromol/l; 2.5-fold), but not by BQ788 (1 micromol/l). In the presence of both antagonists, the dose-response curve to ET-1 was shifted to the right by 4.5-fold. CONCLUSIONS: These functional studies demonstrate that ET-1 is a potent spasmogen of equine third generation pulmonary artery and bronchus, and that contractions are mediated via ETA receptors in the former and both ETA and ETB receptors in the latter. POTENTIAL CLINICAL RELEVANCE: Endothelin receptor antagonists may have potential for treating equine pulmonary hypertension or bronchoconstriction.     

Preliminary pharmacological characterization of ovine mesenteric vasculature

Spirally cut strips of ovine mesenteric vein and artery were studied in isolated organ baths. No qualitative differences were observed in the autonomic and autacoid reactivity of these blood vessels. Both arterial and venous preparations responded in a dose-related manner to 5HT greater than or equal to adrenaline greater than phenylephrine greater than histamine. The responses of venous and arterial strips to 5HT were antagonized by methysergide while mepyramine inhibited histamine-induced contractions. Phentolamine competitively inhibited adrenaline on arteries. Vascular preparations, incubated with mepyramine (2 X 10(-7) M) and contracted half-maximally with 5HT, responded with relaxations to the higher doses of histamine. Specific H2-agonists, impromidine and dimaprit also caused relaxations of half-maximally contracted venous and arterial strips. Impromidine was approximately 500-5000 times more potent than histamine and dimaprit. Trimetaquinol effectively relaxed both venous and arterial preparations while isoproterenol had either no effect or produced weak contractions/relaxations. This investigation suggested the presence of (i) both excitatory and inhibitory receptors for histamine, (ii) D-tryptaminergic receptors mediating contractile effects of 5HT, and (iii) a predominance of alpha-adrenergic receptors, in the mesenteric vasculature of sheep.     

Thermographic study of in vivo modulation of vascular responses to phenylephrine and endothelin-1 by dexamethasone in the horse

REASONS FOR PERFORMING STUDY: In vitro, glucocorticoids potentiate vasoconstriction of equine digital vessels to catecholamines and this has been implicated as a mechanism of glucocorticoid-induced laminitis. This observation has never been confirmed in vivo. OBJECTIVES: To study the effects of glucocorticoid therapy on vasoconstrictor responsiveness in the horse in vivo. METHODS: In a blinded, randomised cross-over experiment, 9 horses were treated with either dexamethasone (0.1 mg/kg bwt i.v. q. 24 h) or saline i.v. for 6 days. The changes in local average skin temperature before (baseline) and after intradermal injections of the alpha1-adrenoceptor agonist phenylephrine (PHE; 10(-4), 10(-5), 10(-6), 10(-7) and 10(-8) mol/l), endothelin-1 (ET-1; 10(-5), 10(-6), 10(-7), 10(-8) and 10(-9) mol/l) or ET-1 plus a blocker (BQ-123 10(-6) mol/l; RES-701 10(-6) mol/l; and L-NAME 10(-4) mol/l) were investigated with a thermograph. RESULTS: Dexamethasone (DEX) decreased baseline skin temperatures, suggesting reduced blood flow as a consequence of an increase in vasomotor tone. This was accompanied by potentiation of the response to PHE as demonstrated by a left shift in the dose-response curve and a decrease in the EC50. Dexamethasone did not potentiate ET-1, but the interplay with the lower baseline temperature resulted in a significantly lower skin temperature for this vasoconstrictor after DEX. The different ET-1 blockers had no effect on ET-1 modulated skin temperatures. CONCLUSIONS: Dexamethasone decreases skin perfusion. This is accompanied by a potentiated alpha1-adrenoceptor agonist response and a greater response to ET-1. POTENTIAL RELEVANCE: Glucocorticoid therapy probably decreases perfusion of the equine hoof. During disease states that already are characterised by hypoperfusion and/or increased levels of circulating catecholamines, glucocorticoid therapy could, according to the vascular model of laminitis, tilt the balance in favour of laminitis.     

Histamine mediates the muscle layer-specific responses in the isolated swine myometrium

To clarify the role of histamine in uterine contractility, the effect of this biogenic amine on the myometrium of cyclic mature gilts was investigated by an isometric tension recording study in vitro. In addition, using crude membrane preparations isolated from the longitudinal (LM) and circular muscle (CM), the distribution of H1 histamine receptors was characterized by ₃H-pyrilamine binding assay. Histamine caused a tetrodotoxin-resistant contractile response of LM and CM in Krebs solution, but LM (-logEC₅₀= 6.34) was more sensitive than CM (-logEC₅₀= 5.4). Pyrilamine decreased the excitatory response of histamine in both muscle layers. In pyrilamine-treated LM, a high concentration of histamine (1-30 μm) caused a slight inhibition of spontaneous contraction, and this inhibition was abolished by ranitidine. On the other hand, histamine did not cause any inhibition in the pyrilamine-treated CM preparations. Dimaprit (10-300 μm) concentration-dependently inhibited the spontaneous contraction of LM but not of CM. In the presence of pyrilamine and ranitidine, N α-methylhistamine, even at 10 μm, did not affect the spontaneous and electrical field stimulation (5Hz)-induced contraction of LM and CM layers. Specific ₃H-pyrilamine binding sites were distributed heterogeneously in the swine myometrium. The maximum number of binding sites in LM (132.5 ± 9.9 fmol/mg protein, n= 10) was 2.5 times higher than that in CM (52.2 ± 3.2 fmol/mg protein, n= 6). These results indicate that there is a muscle layer-dependent difference of histamine-induced response in the swine myometrium. In the LM layer, histamine acts on both H1 and H2 histamine receptors, and causes contraction (via H1 receptors at a low concentration) or relaxation (via H2 receptors at a high concentration in the presence of pyrilamine). However, histamine causes only a contraction in the CM layer, likely the result of the absence of H2 histamine receptors. Histamine-induced contraction is conspicuous in the LM layer, because of the heterogeneous distribution of H1-receptors between LM and CM.     

Influence of the autonomic nervous system in the horse urinary bladder

alpha and beta-adrenergic receptors in detrusor muscle and bladder base of horses were investigated by in vitro responses of smooth muscle strips to exogenous agonist and antagonist drugs. Noradrenaline, isoprenaline and salbutamol induced relaxation of detrusor muscle strips which was significantly inhibited by propranolol and butoxamine suggesting that the response is mediated by beta-2 adrenergic receptors. In the urinary bladder base noradrenaline, phenylephrine and B-HT 920 induced strong contractile effects. These contractile responses were inhibited by the alpha antagonist phenoxybenzamine, the alpha-1 selective antagonist prazosin and the alpha-2 selective antagonist yohimbine. The inhibitory action of prazosin was more potent than that observed with yohimbine suggesting that the response in the bladder base of horses is mediated predominantly by alpha-1 adrenergic receptors, although alpha-2 receptors also participate.     

Adrenergic regulation of vascular smooth muscle tone in calf digital artery

Radioligand binding studies and functional assays on isolated smooth muscle preparations were performed in order to obtain a biochemical and functional characterization of the beta-adrenoceptor (beta-AR) subtypes involved in regulation of the smooth muscle relaxation of the calf's common digital artery. The results indicate that the common digital artery possesses two beta-AR populations (40% beta(1) and 60% beta(2)) and the beta(2)-subtype appears to predominate as far as function is concerned. Only the beta(2)-AR agonists clenbuterol and fenoterol caused dose-related relaxant effects, antagonized by propranolol, when tested in preparations precontracted both with PGF(2alpha) (1.4 x 10(-5) m) and noradrenaline (1.2 x 10(-6) m). In noradrenaline precontracted preparations the beta(1)-AR selective agonists dobutamine and xamoterol caused vasodilation which was not antagonized by (+/-)propranolol. While the functional relaxant effects of dobutamine may be attributed to its potent competitive alpha-AR blocking activity, further investigations are required to explain the effect of xamoterol. The vasodilator effect of (+/-)isoproterenol was irregular. The recorded contractile effects, mainly at dosages greater than 10(-6) m, suggest the loss of drug selectivity for beta-AR and alpha-AR activation. Indirect evidence indicates that the alpha-adrenoceptor (alpha-AR) population in this tissue which produces a strong contraction is functionally dominant over the beta-AR, suggesting limited therapeutic benefit for beta-AR drugs to control blood flow disorders in the calf's distal limb.     

Influence of closure of the reticular groove on the bioavailability and disposition kinetics of meclofenamate in sheep

Sodium meclofenamate is a non-steroidal anti-inflammatory drug with anaphylactic protective activity in cattle. The objectives of this study were to describe the pharmacokinetic behaviour of sodium meclofenamate after intravenous and oral administration to sheep and to determine the influence of closure of the reticular groove on the bioavailability of the drug. Sodium meclofenamate was administered by the intravenous (2.2 mg/kg) and oral (20 mg/kg) routes to sheep (n = 6). During the oral study the reticular groove was closed by intravenous administration of lysine vasopressin (0.3 IU/kg) or left open (saline solution). The closure of the reticular groove was assessed by determination of the blood glucose curves after oral administration of a glucose solution. After intravenous administration of meclofenamate, the distribution and elimination half-lives of the drug were 7.2 min and 542 min respectively, V_ss was 1.68 L/kg and Cl_B was 2.47 mL/min kg. Two different patterns of the plasma concentration curves were observed after oral administration of sodium meclofenamate. When the reticular groove was closed, two peaks were observed ( t _max-2 12-15 min, C _max-1 3.30-24.01 μg/mL; and t _max-2', 52.50-75 min, C _max-2' 6.45-11.08 μg/mL).     

Effects of muscarinic receptor antagonists on acetylcholine-induced contractions of jejunal smooth muscle in horses

This study investigated the effects of a muscarinic type 1 (M(1)), 2 (M(2)), and 3 (M(3)) antagonists (4-DAMP, pirenzepine, and methoctramine, respectively) on acetylcholine (Ach)-induced contractions of longitudinal jejunal muscle strips of horses. Strips were irrigated with Krebs-Henseleit solution gassed with 95% O(2) and 5% CO(2), and the developed tension in response to Ach was recorded before and after incubation with increasing concentrations of 4-DAMP (10(-8)-10(-6) M), pirenzepine (10(-6)-10(-4) M), and methoctramine (10(-5)-10(-3) M). When competitive antagonism was characterized, the affinity constant (pA(2)) was calculated by Schild plots. A parallel rightward shift in the concentration-response curves was observed after 4-DAMP and pirenzepine. Methoctramine presented a dual effect on the concentration-response curves: lower concentrations induced a parallel rightward shift without altering the maximum intensity of contraction (E(max)), while the highest concentration increased slope of the concentration-response curve and increased E(max). The pA(2) for 4-DAMP and pirenzepine was 9.18 and 7.13, respectively. Acetylcholine-induced contractions of longitudinal jejunal smooth muscle are mediated mainly via M(3) receptors. The complex role of M(2) receptors in jejunal smooth muscle contractions was evident because methoctramine potentiated the contractile response to higher doses of Ach.     

Endothelin receptor mediating contraction of isolated bovine coronary artery

We studied endothelin (ET) receptors and their subtypes on isolated bovine coronary arteries. Endothelin receptors that mediated contraction of isolated bovine coronary artery were characterized by the use of antagonists and agonists. Contractions induced by the nonselective agonist ET-1 (10-10-10-7 M) were not affected by the removal of the endothelium (pEC50: 8.52, maximal contraction: 105% of that induced by 60 mM KCl). BQ-123 (3 x 10-7 M) antagonized contractions of endothelium-denuded coronary rings induced by low concentrations of ET-1 (10-10 or 10-9 M), but potentiated the contractions induced by higher concentrations of ET-1 (3 x 10-8 and 10-7 M). BQ-788 (10-6 M) potentiated contractions induced by ET-1 (3 x 10-10 and 10-7 M). In the presence of BQ-788 (10-6 M), BQ-123 (3 x 10-8-3 x 10-6 M) concentration - dependently inhibited contractions induced by ET-1 (3 x 10-10 and 10-7 M) (pA2: 6.61). Sarafotoxin S6b (10-9-3 x 10-7 M) evoked contractions in the denuded coronary artery (pEC50: 8.49, maximal contraction: 139% of 60 mM KCl). The BQ-123 caused a concentration-dependent rightward shift of contractions induced by sarafotoxin S6b (pA2: 7.89). The present study indicates that ET-1 and sarafotoxin S6b contract the isolated bovine coronary artery by stimulating ETA receptors on smooth muscle cells, and that ETB receptors might suppress the ET-1-induced contractions.     

奶牛输卵管平滑肌前列腺素类受体的分析研究

本研究选用了前列腺素类化合物(Prostaglandin E2（PGE2）、Prostaglandin F2α（PGF2α）、Prostaglandin D2（PGD2)）和受体选择性激动剂（Butaprost、U-46619）,用多道生理信号采集系统测定其对体外分离的奶牛输卵管峡部及壶腹部平滑肌收缩的影响,以此初步揭示受体的种类。结果发现,PGE2和Butaprost均抑制了奶牛输卵管峡部、壶腹部的自发性收缩运动,呈现明显的浓度依存性舒张反应;PGF2α在高浓度(1～10 μmol/L)下,使峡部和壶腹部的自发性收缩运动有了显著增强;PGD2在低浓度时轻微抑制了壶腹部平滑肌的收缩,但在高浓度(1～10 μmol/L)时加强了峡部和壶腹部平滑肌的收缩;U-46619从低浓度便引起了输卵管峡部和壶腹部平滑肌的强烈收缩。结果表明,EP4、EP2、FP、DP和TP受体同时存在于奶牛输卵管平滑肌上,能与内源性前列腺素类结合并参与调节输卵管平滑肌的自发性收缩。     

Mechanism of carbon monoxide-induced relaxation in the guinea pig ileal smooth muscle

The mechanism of carbon monoxide (CO)-induced relaxation were investigated in the guinea-pig ileum. CO (10%) inhibited the 40 mM KCl-induced contraction. This effect was antagonized by ODQ (1 microM), a soluble guanylate cyclase inhibitor. In contrast, CO did not inhibit the 40 mM KCl-induced increase in cytosolic Ca2+ level ([Ca2+]i). Cumulative addition of KCl induced a graded increase in both [Ca2+]i and muscle tension. In the presence of CO, the increase in muscle tension was attenuated whereas the increase in [Ca2+]i was only slightly decreased. Thus, the [Ca2+]i-tension relationship constructed by cumulative addition of KCl shifted downwards in the presence of CO. Using the patch clamp, CO was found to have little effect on the peak Ba currents (I(Ba)) when voltage was stepped from -60 mV to 0 mV. From these results, we conclude that CO inhibits contraction of guinea-pig ileum mainly by the decrease in the sensitivity of contractile elements to Ca2+ via a cyclic GMP-dependent pathway but not by the inhibition of L-type Ca2+ channel.     

Electrocardiographic functional diagnosis of the autonomic nervous system in cattle. 1. Electrocardiographic determination of maximum dose for the beta-adrenergic substance isoprenaline

Reference is made to the importance of functional diagnosis of the autonomic nervous system in cattle, and a concept is described by which higher methodological reliability should be obtainable for intra-organic diagnosis of sympathetic nerve activity. What is needed, among others, is to eliminate the autonomous cardiac effect through pharmacological blockade by means of the parasympathetic atropine and the beta-receptor blocker propanolol. The beta-adrenergic substance isoprenaline, required to estimate propranolol blocking action upon the beta-adrenegic receptors, then was injected through indwelling catheters to the external jugular veins of cattle. The doses were between 50 microgram and 560 microgram. Isoprenaline doses between 200 microgram and 250 microgram were established as maximum doses by electrocardiographic examination, determination of heart rate, and clinical observation. Such maximum isoprenaline doses were found to be suitable for checking the extent to which beta-adrenergic blockade of the heart has been caused by beta-receptor blockers. However, sub-maximum isoprenaline doses of something between 100 microgram and 150 microgram should be used to establish the extent to which beta-receptors have caused relaxation of smooth musculature.     

Effects of topical administration of timolol maleate on intraocular pressure and pupil size in cats

Effects of topical administration of a single dose of timolol maleate, a nonselective beta-adrenergic blocking agent, on intraocular pressure (IOP) and pupil diameter were evaluated in the normotensive eyes of 10 clinically normal cats over 12 hours. Mean (+/- SEM) normal IOP was 17.1 (+/- 1.1) mm of Hg and diurnal fluctuation was observed, with the highest IOP seen in the evening. Mean (+/- SEM) normal pupil diameter was 10.1 (+/- 0.5) mm. Topical treatment with 0.5% timolol resulted in reduction of IOP in treated and nontreated eyes. This effect was time-dependent and was first observed at 6 hours after treatment. Mean reduction of IOP was 22.3% in the treated eye and 16.3% in the nontreated eye. The treated eye had reduced pupil diameter at 30 minutes after treatment, and miosis persisted throughout the 12 hours of the study. Mean reduction of pupil diameter was 38.7%. A contralateral effect on pupil diameter was not seen in the nontreated eye. Topical administration of timolol maleate results in a reduction of IOP in treated and contralateral eyes, which supports the use of timolol for treatment of glaucoma in cats. In addition, the treated eye becomes miotic. This effect may indicate beta-adrenergic inhibition or alpha-adrenergic activation of the iris sphincter muscle. beta-Adrenergic blockade would then result in miosis.     

Reticular groove contraction in dairy cattle following drenching with an anti-bloat solution or a combination of anti-bloat solution and NaCl

AIM: To determine whether the inclusion of NaCl in an antibloat drench increased the incidence of contraction of the reticular (oesophageal) groove in cattle. METHODS: Non-lactating Friesian dairy cows aged 3-10 years (n=30) were subjected to a 13C-octanoic-acid breath test after being drenched with either an anti-bloat solution alone or a mixture of anti-bloat solution and NaCl, to determine the incidence of reticular groove contraction. RESULTS: Drenching with an anti-bloat solution alone did not result in detectable by-pass of the reticulorumen in 27/29 cows; minor by-pass occurred in 2/29 cows. The inclusion of NaCl in the anti-bloat solution increased the incidence of reticulorumen by-pass; minor by-pass occurred in 12/30 cows and substantial by-pass was detected in 5/30 cows. The incidence of by-pass did not vary significantly with cow age. CONCLUSIONS: Drenching with an anti-bloat solution alone did not result in significant by-pass of the reticulorumen. The inclusion of NaCl in the anti-bloat drench increased the incidence of reticulorumen by-pass. The proportion of anti-bloat/ NaCl fluid by-passed was considered to be of no practical significance to the protection from bloat afforded in the majority of animals, but may significantly decrease protection from bloat afforded by drenching in 10-15% of cows. The proportion of animals at risk within a herd may vary with their physiological state and the method and frequency (number of doses per drench) of drenching.     

Electrocardiographic functional diagnosis of the vegitative nervous system in cattle. 2. Determination of the propranolol blockade effect on cardiac beta-receptors under application of maximum isoprenaline doses]

The blocking effects of 50 mg and 100 mg of propanolol, a beta-receptor blocker, upon the beta-adrenergic receptors of cattle heart were verified by means of 250 microgram of isoprenaline, a maximum dose. The 50-mg-propanolol dose inhibited between 77 and 80 per cent of the isoprenaline-caused QT reduction, whic action was considered as being sufficiently safe to rule out any beta-adrenergic cardiac effect. Blockade was further increased to the order of between 89 and 92 per cent by using 100 mg of propanolol, but certain side-effects occurred (expiratory dyspnoe, quinidinlike action in terms of PQ extension, and vagovasal collapse). Therefore, 50 mg of propanolol are recommended as the proper dosage with which to examine cardiac and extracardiac beta-adrenergic receptors in cattle. Application of propanolol to non-anaesthetised, nonatropinised cattle resulted in higher bloackade of isoprenaline-caused QT reduction, as compared to the parameters PQ, TP, TQ, time of cardiac action, PP, and momentary heart rate. This phenomenon is being analysed. With reference being made to the peculiarities of sympathico-parasympathetic interactions on the heart, QT time is considered as a more safe parameter by which to assess substrate competition between propanolol and isoprenaline at cardiac beta-receptors, while the ventriculodiastolic ECG recordings TQ, TP, and PQ as well as time of cardiac action, PP and momentary heart rate might come under a somewhat stronger influence of the parasympathetic system.     

Effects of bethanechol on canine urinary bladder smooth muscle function

We studied whether the effects of bethanechol are mediated via a muscarinic receptor, the role of extracellular calcium on bladder contraction, and down-regulation of bladder contraction by bethanechol after activation with potassium chloride (KCl) and acetylcholine (Ach). Smooth muscle strips of normal urinary bladder were studied with standard methods to measure isometric force. Bethanechol caused a dose-dependent increase in bladder contraction. The potency of bethanechol is higher than Ach, as shown by higher peak active isometric stress (P(max)) and lower half-maximal contraction (ED(50)) (P< 0.01). The contractile responses to bethanechol were diminished in the presence of atropine, nifedipine and in calcium-free medium as shown by P(max) decreased by 58%, 87% and 65% and ED(50) increased by 314-, 24- and 16-fold, respectively. When bladder strips were stimulated with KCl and Ach, pre-treatment with bethanechol reduced the responses to KCl by 116-242% (P<0.05), while the contractile responses to Ach were unaltered. Thus, bethanechol induces bladder contraction via muscarinic receptor activation while both intracellular and extracellular calcium play a crucial role on bladder smooth muscle contraction. The mechanisms of down-regulation by bethanechol may be related to interference with calcium influx into the smooth muscle cells, rather than the desensitisation of muscarinic receptors or post-receptor steps of signal transduction following bethanechol binding to the receptor.