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PubMed1959

The actions of bretylium: adrenergic neurone blocking and other effects.

Bretylium caused a specific and lasting depression of many excitatory and inhibitory responses evoked by electrical stimulation of the peripheral sympathetic nervous system, probably by impairing conduction of impulses in adrenergic neurones with consequent failure of noradrenaline and adrenaline release. This effect, which will be referred to as the adrenergic neurone blocking action, was preceded by weak sympathomimetic effects. In the presence of bretylium the effects of adrenaline and noradrenaline were increased, as after sympathectomy. Concentrations producing blocking of adrenergic neurones did not prevent the release of adrenaline and noradrenaline from the adrenal medulla by splanchnic nerve stimulation or by the injection of dimethylphenylpiperazinium iodide, nor did they cause antiparasympathetic or parasympathomimetic effects. No action on the central nervous system has been detected. Curare-like neuromuscular block occurred with 10 to 30 times the amount required to block the response to adrenergic nerve stimulation alone and was accompanied by signs of temporary synaptic block in autonomic ganglia. Adrenergic nerve trunks and sensory nerves in the skin were readily blocked for long periods by topical application of bretylium, whereas the phrenic nerve of the rat was not. Bretylium had little effect on gastrointestinal propulsion or on the sensitivity of smooth muscle to acetylcholine, 5-hydroxytryptamine, adrenaline, or noradrenaline, but moderate amounts depressed the peristaltic reflex and the sensitivity of the guinea-pig ileum to histamine. Bretylium caused postural hypotension in the cat in doses which had little effect on the supine blood pressure. Experiments on the nictitating membrane indicated that compensation for the effects of bretylium on low rates of stimulation of postganglionic sympathetic nerves could be attained by a small increase in the rate of stimulation, whereas compensation for its effects on high rates required an increase in the rate of stimulation beyond physiological limits.

Acetylcholine↗

PubMed1959

Nicotine and the effect of antisympathomimetic agents on the aorta of the rabbit.

The responses of strips of rabbit aorta to almost maximal doses of nicotine were less readily antagonized by five antisympathomimetic agents than were comparable responses to noradrenaline. The effect was most marked with dibenamine, ergotamine, and tolazoline: approximately twice the dose of noradrenaline was required to match the test dose of nicotine after treatment with the antagonists. Dose/response curves for nicotine before and after phentolamine 10(-7) indicate that the phenomenon may be reversed with low doses of nicotine and that the release of noradrenaline by nicotine within the tissues is probably a graded response. The pattern of nicotine/phentolamine antagonism in this preparation is consistent with the view that nicotine acts indirectly by releasing a noradrenaline-like substance, and the difficulty found in antagonizing responses to nicotine with antisympathomimetic agents is probably similar to that responsible for failure of atropine to block some parasympathomimetic responses to nicotine.

Animals↗

PubMed1972

The presence of -adrenoceptors in the guinea-pig seminal vesicle.

1. The preparation of longitudinal smooth muscle strips from guinea-pig seminal vesicles is described.2. Isoprenaline and salbutamol inhibited contractions produced by parasympathomimetic agents.3. The inhibitory action of isoprenaline was blocked by low concentrations of propranolol and butoxamine. It was concluded that beta(2)-adrenoceptors were present in the tissue.4. The inhibitory action of isoprenaline was not apparent when adrenaline, noradrenaline, hypogastric nerve or transmural stimulation were used to contract the tissue.

Acetylcholine↗

PubMed1989

Effect of endothelium removal on stimulatory and inhibitory modulation of rat aortic prostacyclin synthesis.

1. Removal of the endothelium (DE) enhanced the in vitro release of prostacyclin (PGI2) by rat aortae in response to adrenaline (Ad), noradrenaline (NA), thromboxane A2 analogue U46619, phorbol dibutyrate (PDBU) and sodium fluoride (NaF) when assessed at 3 h post DE. At 6 h post DE, there were no differences between the dose-response curves obtained from aortic rings with or without endothelium. 2. At 3 h post DE the antagonism of Ad- and NA-stimulated PGI2 synthesis by yohimbine and prazosin, and NA-stimulated PGI2 synthesis by nifedipine was markedly reduced in aortae without endothelium when compared with controls. These effects were reversed by protracted incubation of aortic tissue post DE (6 h and 9 h). 3. Acetylcholine, carbachol, substance P and nitroprusside were without effect on de novo or NA-stimulated PGI2 synthesis, whether or not the endothelium was present and irrespective of incubation time, post-DE. 4. These results indicate that: (a) PGI2 synthesis linked to excitatory receptors (alpha-adrenoceptors, thromboxane A2) and associated systems (G proteins, protein kinase C) in the smooth muscle component of the rat aorta is not influenced by endothelium-derived relaxing factor (EDRF); (b) the changes of response to stimulators and inhibitors of PGI2 synthesis may be due to an increased reactivity of the vessels caused by the trauma of DE; and (c) vasodilators (parasympathomimetics, substance P and nitroprusside) that do not act directly on excitatory receptors do not influence PGI2 synthesis.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1985

Supersensitivity to methacholine in rat urethra following hypertrophy or disuse.

It has been possible to sensitize the rat urethra without cutting its nerves. This was achieved by hypertrophy or disuse. Hypertrophy of the urethra (2-4-fold weight increase) was caused by the presence of an intraluminal paraffin bolus. Disuse was caused by diverting the flow of urine from the lower urinary tract. When examined in vitro after an experimental period of 1 to 4 weeks the EC50 value of the parasympathomimetic drug methacholine was in both cases half of that of controls. The common cause of the development of supersensitivity in the two types of experiments is thought to be decreases in the local concentration of transmitter at the muscle cells. The present findings favour the idea of a parasympathetic motor control of the rat urethra.

Animals↗

PubMed1977

Choline acetyltransferase activity in parotid glands of rats after prolonged treatment with pilocarpine.

The enzyme activity, expressed as total activity and concentration, was found to be decreased in the cholinergic neurones of the glands after treatment with pilocarpine for 10 days. The secretion of saliva evoked by the parasympathomimetic drug is thought to have reduced the reflex stimulation of the glands via the cholinergic secretory nerves and thereby lowered the enzyme activity in the nerves.

Acetyltransferases↗

PubMed1980

Amylase secretion in response to activation of different autonomic receptors in the rabbit parotid gland.

The contribution by different autonomic receptors to the amylase secretion from the parotid gland of the anaesthetized rabbit was studied as the response to various parasympathomimetic and sympathomimetic drugs. Amylase secretion by infusions of pilocarpine and parasympathetic nerve stimulation was low, but regularly higher in response to pilocarpine than to parasympathetic nerve stimulation. These effects were reduced to the same level by beta-adrenoceptor block indicating the presence and for pilocarpine also the release of catecholamines, probably from the adrenals. Isoprenaline injections produced a high amylase secretion, that was blocked by atenolol, indicating that predominantly beta 1-adrenoceptors were activated. Phenylephrine was without amylase secretory effects. By accepting isoprenaline maximum as maximum for sympathetically produced amylase secretion, a theoretical frequency-response relationship for amylase secretion by sympathetic nerve stimulation could be calculated: ED50 was 0.9 Hz. The results indicate that under experimental conditions in vivo there are certain differences between the rat and the rabbit parotid glands in the autonomic control not only of fluid, but particularly of amylase secretion.

Amylases↗

PubMed1981

Preponderance for either alpha- or beta-adrenoceptor mediated sensitization in the rat submaxillary gland.

The sensitivity of the rat submaxillary gland was examined 3-4 weeks after either parasympathetic decentralization or sympathetic decentralization or denervation. The threshold doses for secretion of saliva of parasympathomimetic (methacholine) and sympathomimetic (noradrenaline, adrenaline, phenylephrine and isoprenaline) drugs were estimated and the amount of saliva secreted in response to supraliminal doses of these drugs was measured. Each type of operation caused the development of a supersensitivity that involved all three types of receptors, i.e. muscarinic cholinoceptors, alpha-adrenoceptors and beta-adrenoceptors. Following parasympathetic decentralization the sensitization was predominantly mediated via alpha-adrenoceptors, and also via cholinoceptors. Following sympathetic decentralization or denervation the postjunctional sensitization was predominantly mediated via beta-adrenoceptors; most of the supersensitivity to noradrenaline, adrenaline and phenylephrine found after sympathetic denervation was of the prejunctional type. An increase in receptor density and an intracellular arrangement where the response of cholinoceptors and alpha-adrenoceptors is mediated via one pathway and the response of beta-adrenoceptors via another are suggested as factors that may be of importance for the development of the postjunctional supersensitivity. The present study shows that the traffic of secretory impulses in the sympathetic nerve is of importance for the level of sensitivity of the secretory cells. Since postjunctional supersensitivity following sympathetic denervation did not exceed that following sympathetic decentralization it is suggested that under normal conditions a continuous release of noradrenaline from the nerve endings is of little importance for the level of sensitivity.

Animals↗

PubMed1984

Development of supersensitivity to methacholine in the rat detrusor following either parasympathetic denervation or decentralization.

The male rat urinary bladder belongs to those few structures where both the post- and preganglionic parasympathetic nerves are accessible for severance. In the present study the sensitivity to the parasympathomimetic drug methacholine of muscle strips of either denervated or decentralized bladders was examined in vitro. One week postoperatively denervated and decentralized bladders were sensitized to the same degree, the ED50 values being 4 times less than ED50 of unoperated control bladders. In contrast to the decentralized bladders the supersensitivity in the denervated ones was found to have increased further when tested four weeks postoperatively, the ED50 value being about 20 times less than that of controls. The present findings are in agreement with Cannon's "law of denervation". The results are discussed in relation to possible mechanisms behind the phenomenon of supersensitivity.

Animals↗

PubMed1994

Depletion of secretory granules from the feline parotid gland: action of NANC transmitters per se.

A parotid acinar degranulation of approximately 60 and 40% was observed in cats under pentobarbitone anaesthesia after a 90-min period of continuous stimulation of the parasympathetic auriculo-temporal nerve at 10 Hz in the absence and presence of atropine, respectively. Atropine completely abolished the large fluid response of the gland to the nerve stimulation. In the non-atropinized cats, bethanechol, infused into the carotid artery at a dose rate evoking a salivary flow similar to that in response to parasympathetic nerve stimulation, caused an acinar degranulation of approximately 25% and acinar vacuolation. Vasoactive intestinal peptide (VIP; 0.5 microgram kg-1 min-1 also infused into the carotid artery for 90 min) caused an acinar degranulation of the same magnitude as the parasympathomimetic drug but the peptide did not give rise to any fluid secretion or vacuole formation. The experiments were performed in the presence of alpha- and beta-adrenoceptor blockers. Thus, in parotid glands of the cat, producing no overt secretion of fluid, non-adrenergic, non-cholinergic (NANC) mechanisms may be at work causing exocytosis of the acinar granules. These mechanisms are also likely to contribute to the secretion of granules in response to parasympathetic nerve activity in the absence of blockade of the classical autonomic receptors.

Adrenergic alpha-Antagonists↗

PubMed1998

Idiopathic detrusor-urethral dyssynergia in dogs: a retrospective analysis of 22 cases.

Results of a retrospective study of 22 dogs with signs of dysuria and/or stranguria in which a diagnosis of idiopathic detrusor-urethral dyssynergia was made are presented. The diagnosis was based on the exclusion of detectable pathological conditions which could also cause urine outflow obstruction. The affected cases were 22 middle-aged male dogs (mean age 4.9 years) of large and giant breeds (mean bodyweight 36.7 kg). Nine dogs had had periodic clinical signs for longer than one year, one for seven months and eight for two to five weeks, while in four dogs signs had begun four to five days before referral. All dogs received the alpha-sympatholytic agent prazosin as an initial treatment and in 11 it remained the only therapy. There was a good effect in seven and a moderate response in the other four dogs. In one dog, prazosin was ineffective and was replaced by diazepam, which markedly reduced the signs. Three other dogs required frequent catheterisation and antibiotics were administered. These dogs responded favourably. Another three dogs with evidence of impaired bladder contractility were also treated with the parasympathomimetic agent carbachol. One did not improve and was euthanased. Four dogs developed bladder paralysis and severe infectious cystitis. Only one of these could be managed satisfactorily by long-term administration of prazosin, carbachol and antibiotics, and the others had to be euthanased.

Animals↗

PubMed1994

Cardiac response to autonomic drugs in atria of diabetic mouse.

Comparisons of chronotropic effects of sympathomimetic and parasympathomimetic agents were made in isolated atria from alloxan-induced diabetic and age-matched control mice. In atria from mice rendered diabetic for three months, the cardiac response to bethanechol was potentiated compared with that of the age-matched control atria. However, the cardiac responses of atria from alloxan-treated mice to noradrenaline, 3-isobutyl-1-methyl-xanthine and 1,1-dimethyl-4-phenyl piperazinium iodide were similar to those of the controls.

1-Methyl-3-isobutylxanthine↗

PubMed1966

The dependence of the action potential of the frog's heart on the external and intracellular sodium concentration.

1. The overshoot of the action potential of the frog's heart was reduced when external sodium chloride was replaced by sucrose. However, the potential decrement was only 17.3 mV for a 10-fold reduction of sodium as compared with 58 mV expected on the basis of the sodium hypothesis of excitation.2. Replacement of up to 75% of the external sodium by choline did not reduce the overshoot, provided atropine was present in sufficient concentrations to suppress any parasympathomimetic action.3. The maximum rate of rise of the action potential markedly declined in low sodium fluids whether sucrose or choline chloride was used to replace sodium chloride.4. The maximum rate of rise was reduced to only a small extent when external sodium was replaced by lithium.5. Increasing the intracellular sodium concentration in exchange for lost potassium caused overshoots to decline. The effects resembled those obtained in similar experiments with skeletal muscle fibres (Desmedt, 1953).6. Action potentials occurring under certain conditions even in the presence of very low external sodium concentrations (</= 5% normal) also declined in height when the intracellular sodium concentration was increased.7. The behaviour of the action potential in low external sodium concentrations may be explained by an action of calcium on the excitable membrane.

Animals↗

PubMed1993

Experimental myopia in a diurnal mammal (Sciurus carolinensis) with no accommodative ability.

1. We examined the functional morphology of the intra-ocular muscles of the grey squirrel using pharmacological and histological methods. Using sympathomimetic (phenylephrine) and parasympathomimetic (carbachol) agents, administered by transcorneal iontophoresis, the response of the iris sphincter and dilator muscles and the ciliary muscle were recorded. Measurement techniques included both streak retinoscopy and coincidence optometry for measurement of ocular refraction and high resolution ultrasonography to monitor changes in the intra-ocular component dimensions. 2. The grey squirrel was found not to possess a functional accommodative system. No change in ocular refraction or intra-ocular dimensions could be induced with 40% carbachol. Marked changes in pupil diameter occurred with topical application of both phenylephrine (dilation) and carbachol (constriction). Histological findings were in agreement with pharmacological findings in showing well developed iris sphincter and dilator muscles but only a poorly developed ciliary muscle. 3. Calculation of the depth of focus of the grey squirrel eye reveals that this could be sufficient to account for the behavioural observations of near viewing habits. 4. We then determined whether we could induce axial elongation of the vitreous chamber and a consequent myopia by monocular deprivation (MD) of pattern vision. 5. Monocular deprivation of pattern vision produced a significant experimental myopia due to axial elongation of the vitreous chamber in the deprived eye. 6. The results demonstrate that a functional accommodative system is not necessary to induce experimental myopia in the grey squirrel eye.

Accommodation, Ocular↗

PubMed1975

Miotics in closed-angle glaucoma.

The use of intravenous Diamox with variable doses of Pilocarpine was investigated in the treatment of primary closed-angle glaucoma. It was concluded that one drop of Pilocarpine 3 to 4 hrs after intravenous Diamox is the only parasympathomimetic drug necessary to terminated an acute attack.

Acetazolamide↗

PubMed1973

Hypersecretion of zymogen granules in the pathogenesis of cystic fibrosis.

In the submandibular saliva of 10 cystic fibrosis subjects and 10 controls the turbidity and elevated calcium, protein, and amylase concentrations of the cystic fibrosis secretions, and precipitation of calcium and phosphate in a ratio consistent with hydroxyapatite have been confirmed. By electron microscopy the centrifuged deposits of the cystic fibrosis saliva were seen to be composed predominantly of round or oval subcellular corpuscles. By comparison with submandibular gland, these corpuscles have been identified as inclusion bodies (spherules) from within zymogen granules. Hydroxyapatite crystals formed on standing in the cystic fibrosis saliva. Polyacrylamide gel disc electrophoresis of the cystic fibrosis centrifuged deposits showed five bands, one of which, band 4, was more prominent in the deposit than in the supernatant gels. Comparisons have been made between these results and other studies and have shown (1) elevated calcium and protein in cystic fibrosis exocrine secretions; (2) simultaneous secretion of calcium and enzymes from salivary glands, stomach, and pancreas; and (3) increased salivary secretion of calcium and protein in response to parasympathomimetic and sympathomimetic drugs. Hypersecretion of calcium-containing zymogen granules is postulated as the cause of obstruction in cystic fibrosis.

Adolescent↗

PubMed1978

Effect of autonomic agents on the amount of androgen-dependent granules in convoluted tubular cells of the mouse submandibular gland.

The convoluted tubular cells of the male mouse submandibular gland contain many serous-like granules in their apical cytoplasm. The autonomic regulation of the secretory process of the contents of these granules was studied by the following two methods: (1) immunochemical method using an antiserum specific to the granular components; and (2) histometric observations using light and electron microscopes. The results obtained by these two methods were well in agreement. When male mice were administered either phenylephrine or norepinephrine, the amount of granules in the glands significantly decreased. These two adrenergic stimulators were very effective, whereas synephrine was less effective. When mice were injected with a beta-adrenergic agent(isoproterenol) or a parasympathomimetic agent (pilocarpine), the amount of granules in the glands did not change. The alpha-adrenergic blockers phenoxybenzamine and phentolamine almost completely neutralized the effect of alpha-adrenergic agents on the glands, whereas another alpha-blocker (ergotamine) was less effective. These facts suggest that the secretion of the granular components is mediated by way of alpha-adrenergic receptor sites in the glands.

Adrenergic alpha-Agonists↗

PubMedDate not supplied

Modification of cardiovascular function in dogs by acupuncture: a review.

Acupuncture at Jen Chung (Go-26) in dogs under halothane anesthesia produces sympathomimetic-like effects on the cardiovascular system. This response can be inhibited by pretreatment with propranolol and to a lesser extent with phentolamine. Severe hypotension and cardiac arrest produced by hypoxia in dogs under halothane anesthesia can be reversed by acupuncture at Jen Ying (St-9). This also was interpreted as a sympathomimetic-like effect. Acupuncture at Tsu San Li (St-36) results in a parasympathomimetic-like effect on the cardiovascular system which can be inhibited by atropine. A parasympatholytic-like effect resembling that produced by atropine can be obtained in dogs with sinus arrhythmia and pulsus alternans by acupuncture at Yang Hsi (LI-5).

Acupuncture Therapy↗