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Biomedical subjects

C A Maggi

Publications and source records attributed to C A Maggi.

At least 577 records · Page 32Linked to original sources
PubMed1984

Postnatal development of myogenic contractile activity and excitatory innervation of rat urinary bladder.

Bladder strips from newborn compared with adult rats exhibited marked differences in both myogenic properties and postganglionic excitatory innervation. In the first 2-wk of life myogenic contractile activity progressively changed from a quiescent state (at birth) to the asynchronous contractile activity typical of bladder strips from adult animals. After birth activation of muscarinic cholinoceptors changed the myogenic contractile activity in a manner similar to that observed at later stages of development. Neurogenic contractions of bladders from newborn animals were atropine sensitive in the whole range of frequencies studied. During the first 2 wk the atropine-resistant component of these contractions increased progressively to reach an adult-like condition, i.e., atropine-resistant contractions account for over 90% and approximately 60% of contractions elicited at 0.1 and 1-20 Hz, respectively.

Aging↗
PubMed1984

System and organ-selectivity of smooth muscle relaxants on in vitro spontaneously contracting preparations.

The effects of verapamil, papaverine and octylonium bromide on amplitude and frequency of spontaneous contractions of rabbit duodenum and rat colon, portal vein and right atria have been investigated. Myogenic nature of spontaneous contractions was demonstrated by their resistance to tetrodotoxin (100 micrograms/ml) and hexamethonium (10(-4) M). Verapamil (10(-7) - 5 X 10(-6) M) reduced, in a concentration-dependent manner, amplitude and frequency of spontaneous contractions with a certain degree of selectivity for duodenal preparations. Automaticity of rat right atria was affected by concentrations of verapamil higher than those required to modify automaticity of intestinal preparations. Papaverine (3 X 10(-6) - 3 X 10(-4) M), was almost equipotent in reducing the amplitude of spontaneous contractions of each preparation but inhibited the frequency of contractions in the following order: colon greater than duodenum greater than atrium. Octylonium bromide (10(-6) - 10(-4) M) was characterized by its greater effectiveness in reducing frequency and amplitude of spontaneous contractions of rat colon as compared to the other preparations. All three smooth muscle relaxant drugs, in spite of concentration-related reduction in amplitude, determined a parallel enhancement of frequency of spontaneous contractions in rat portal vein. Differences in drug selectivity are discussed in terms of different roles played by various Ca++-dependent processes (which constitute the cellular target of action of these smooth muscle relaxant drugs) in the genesis of frequency and amplitude of myogenic contractions in the various preparations.

Animals↗
PubMed1984

Evidence for the involvement of arachidonic acid metabolites in spontaneous and drug-induced contractions of rat urinary bladder.

The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and endogenous arachidonic acid (AA) depletion on spontaneous and drug-induced contractions of the rat urinary bladder have been determined by both in vivo and in vitro experiments. Our results suggest that some AA metabolites (presumably prostaglandins) are involved in the physiologic regulation of the micturition reflex in the rat. In vivo findings indicate that the ability of various NSAIDs to inhibit distension-induced rhythmic contractions is proportional to their anti-inflammatory effectiveness. NSAIDs administration or depletion of endogenous AA at the detrusor muscle level by essential fatty acid-free diet (EFAFD) decreased the responsiveness of the urinary bladder to reflex activation. Topical AA triggered a series of neurogenic rhythmic contractions in the preparation which failed to respond to saline loading. This effect was prevented by NSAID pretreatment. The effect of topical AA was mimicked in NSAID-treated preparations by topical prostaglandins. Both NSAIDs and EFAFD reduced the responsiveness of the rat urinary bladder to acetylcholine and purinergic stimulation in vivo and in vitro. NSAIDs enhanced, while EFAFD reduced, the responsiveness of the isolated bladder to stable cholinomimetics. Responsiveness to KCl was unaffected by NSAIDs or EFAFD. These latter findings indicate that either blockade of AA metabolism along the cyclooxygenase pathway or endogenous AA depletion might alter bladder responsiveness at the postjunctional level. However, because the amplitude of distension-induced rhythmic contractions is unaffected by NSAIDs or EFAFD, it appears unlikely that endogenous prostanoids play a role in excitatory neurotransmission or in tension development during physiological-like activation of the bladder muscle. In vitro findings indicate that both NSAIDs and EFAFD reduce the myogenic contractility and the responsiveness to stretch of bladder muscle. These findings are suggestive that AA metabolites could regulate micturition by enhancing the amplitude of the myogenic contractions of the bladder muscle and, consequently, the discharge of vesical afferents to the central nervous system.

Adenosine Diphosphate↗
PubMed1984

The effect of urethane on spontaneous and stimulated contractions of isolated rabbit urinary bladder.

The effects of urethane on the spontaneous and stimulated contractility of isolated strips from rabbit urinary bladder has been investigated to assess if, and at which concentrations, this anaesthetic interferes with the contractility of the bladder smooth muscle. Urethane produces a generalized depression of both spontaneous and stimulated bladder muscle contractility but is expected that, in concentrations similar to those found in plasma during anaesthesia, its effect does not exceed the 10-20% inhibition. Urethane depression of bladder muscle contractility appears attributable, at least in part, to an inhibition of calcium ions mobilization from an intracellular store.

Animals↗
PubMed1983

Contribution of cellular and extracellular Ca2+ during 5-hydroxytryptamine-induced contractions of rabbit ear artery.

The ability of 5-hydroxytryptamine (5-HT) as compared to norepinephrine (NE) to mobilize different Ca2+ pools was investigated in rabbit ear artery (REA). 5-HT appears to both mobilize intracellular Ca2+ and trigger transmembrane Ca2+ influx in this preparation. Although stimulation of alpha-adrenoceptors by 5-HT appears to be involved, the duration of 5-HT-induced cellular and extracellular Ca2+-dependent contractions outlasts the duration of those produced by equipotent concentrations of NE. Both cellular and extracellular Ca2+-dependent contractile responses produced by low but not high concentrations of 5-HT were significantly higher in arterial segments pretreated with 6-OH dopamine and in presence of desoxycorticosterone and propranolol while those produced by NE were unaffected. The duration of extracellular Ca2+-dependent 5-HT and NE-induced contractions was enhanced over the whole concentration range and in a similar manner. These findings as well as the results obtained with the receptor antagonists cyproheptadine and phentolamine could be interpreted as an indication that: (a) stimulation of alpha-adrenoceptors by 5-HT is only in part responsible for the contractile effects of 5-HT in REA; (b) additional mechanism(s) activated by 5-HT appear to modulate the duration of both cellular and extracellular Ca2+-dependent contractions and, (c) difference(s) in tissular handling of these amines do not appear to play a role in their different contractile effects.

Animals↗
PubMed1983

Reserpine-induced detrusor hyperreflexia: an in vivo model for studying smooth muscle relaxants at urinary bladder level.

A new in vivo model for studying the effects of smooth muscle relaxant drugs at urinary bladder level has been developed. This involves the determination of a cystometrogram at a physiological filling rate in urethane anesthetized rats. The amount of infused saline required to elicit TTX-sensitive rhythmic contractions (micturition reflex) of urinary bladder was choosen as end point to evaluate the effect of test substances. Reserpine pretreatment significantly reduced the volume of saline required to elicit the micturition reflex. The effect of reserpine can be reproduced by intravenous prazosin, but not by propranolol or yohimbine, in control rats. Intravenous, but not topical, hexamethonium reversed the effects of reserpine pretreatment on the amount of infused saline required to elicit rhythmic contractions. The nature of rhythmic contractions produced by saline filling of the urinary bladder in these experimental conditions, as well as the potential mechanism(s) involved in the effects of reserpine, are discussed in view of the existing literature on the physiology and pharmacology of the micturition reflex. The effects of various drugs commonly used to produce a relaxation of bladder muscle suggest that this model might be useful for detecting substances of potential therapeutic usefulness in the treatment of bladder hypermotility disorders.

Animals↗
PubMed1983

The effect of peripherally administered GABA on spontaneous contractions of rat urinary bladder in vivo.

Intravenous GABA suppresses the spontaneous contractions of rat urinary bladder produced by saline loading (micturition reflex) without possessing any significant inhibitory effect on spontaneous and stimulated (neuro-hormones and field stimulation) contraction of rat detrusor strips in vitro. The in vivo effects of GABA, in view of the results obtained with atropine, hexamethonium and tetrodotoxin in the same experimental conditions, are likely to be ascribable to an action at pelvic ganglia level.

Animals↗
PubMed1983

The effects of clonidine on electrically-induced contractions of rat detrusor strips in vitro.

Clonidine (10(-9)-3 X 10(-6) M) produced a concentration dependent inhibition of field stimulation-induced contractions of rat detrusor muscle strip at 0.1 and 1 Hz which were completely abolished by tetrodotoxin (5 X 10(-7) M) but were unaffected by hexamethonium (10(-5) M). Pretreatment with yohimbine (10(-8)-10(-7) M) did not modify the amplitude of contractions but produced a rightward parallel shift of clonidine's cumulative response curve without a depression of the maximal response. The corresponding pA2 value for yohimbine was 8.44 +/- 0.1. Atropine (3 X 10(-6) M) produced a partial inhibition of contractions at both frequencies. In the presence of atropine the cumulative response curve of clonidine was significantly reduced at 1 but not at 0.1 Hz. Indomethacin (5 X 10(-5) M) and theophylline (2 X 10(-4) M) produced a partial inhibition of amplitude of contractions at both frequencies without any interference with the effect of a supramaximal concentration of clonidine. Prazosin (10(-6) M), propranolol (10(-6) M), chlorpheniramine (10(-6) M), ranitidine (10(-6) M), haloperidol (10(-7) M), pizotifen (10(-6) M), naloxone (10(-6) M), quinidine (10(-6) M), strychnine (10(-5) M) or picrotoxin (10(-5) M) neither affected the amplitude of contractions at either frequency nor antagonized clonidine effects. The contractile response of non stimulated strips to acetylcholine (10(-5) M), carbachol (3 X 10(-6) M) and ATP (10(-3) M) were not significantly influenced by pretreatment with clonidine (3 X 10(-6) M). These results suggest that stimulation of prejunctional alpha 2-adrenoreceptors located on postganglionic nerve endings might reduce the output of excitatory neurotransmitter(s) in rat urinary bladder.

Acetylcholine↗
PubMed1983

Alpha-adrenoceptor subtypes and Ca2+ mobilization in the rabbit ear artery.

The mobilization of cellular and extracellular Ca2+ pools by selective alpha 1-adrenoceptor (phenylephrine) and alpha 2-adrenoceptor (xylazine) agonists as well as noradrenaline was evaluated in rabbit ear artery. Noradrenaline and phenylephrine possess full intrinsic activity for both types of Ca2+ mobilization whereas xylazine up to 1 mM had only a limited contractile effect, being more effective in inducing extracellular Ca2+-dependent response. However, extracellular Ca2+ was mobilized by xylazine in a concentration 20 times higher than that required to stimulate pre-junctional alpha 2-adrenoceptors. Noradrenaline (5 microM) and xylazine (1 mM) induced cellular and extracellular Ca2+-dependent contractions which were prazosin-sensitive and yohimbine-resistant. Xylazine-induced contractile activity, particularly that dependent upon the extracellular Ca2+ pool, was markedly reduced by selective adrenergic denervation with 6-hydroxydopamine, but the actions of noradrenaline were unaffected. These results suggest that: (1) rabbit ear artery contain post-junctional alpha 1-adrenoceptor but not alpha 2-adrenoceptors; (2) stimulation of these alpha 1-adrenoceptors can account for the overall contractile activity of exogenously added noradrenaline and (3) stimulation of alpha 1-adrenoceptors results in mobilization of cellular as well as extracellular Ca2+ pools.

Animals↗
PubMed1983

Beta-adrenoreceptor blockers and CaCl2-induced arrhythmias in the rat: discrepancies between antiarrhythmic properties and survival rate.

Although propranolol antagonized CaCl2-induced arrhythmias in the rat due to its local anaesthetic properties, arrhythmias-protected animals died because of respiratory failure. To assess the relative role played by beta 2-adrenoreceptor blocking and local anaesthetic properties in the genesis of this phenomenon, five beta-blockers with different degrees of local anaesthetic properties have been tested at their respective ED50 against CaCl2-induced arrhythmias in the rat and their respective surviving/arrhythmias-protected animals ratio (SAPAR) calculated. A highly significant correlation exists between local anaesthetic properties and SAPAR but not between SAPAR and beta 2-adrenoreceptor blocking properties. Further studies showed that (a) assisted ventilation but not picrotoxin or terbutaline pretreatment protected rats against propranolol-CaCl2-induced respiratory failure, and (b) intracerebroventricular propranolol failed to antagonize CaCl2-induced arrhythmias while producing a dose-dependent inhibition of breathing rate. These results suggest that, in this test model, local anaesthetic properties of beta-blockers are responsible for their antiarrhythmic effect at peripheral level, and superimpose to the effects of CaCl2 in inducing respiratory failure at central level.

Adrenergic beta-Antagonists↗
PubMed1983

The effects of nifedipine and verapamil on high K+ induced contractions of the rat intestinal tract in vivo.

The effects of intravenous nifedipine and verapamil against the contraction produced by topical application of 54 mM K+ on the outer surface of rat duodenum, jejunum, ileum, caecum, colon and rectum have been investigated. Both drugs exhibited a descending gradient of relaxant activity with the exception of the rectum, verapamil being 1/3-1/4 as potent as nifedipine in all the test systems studied. Since these drugs at effective spasmolytic doses significantly affect heart rate and systemic blood pressure, their use as smooth muscle relaxants in intestinal disturbances would present several drawbacks.

Animals↗
PubMed1983

Assessment of potential selectivity of antispasmodics for the various sections of the gastrointestinal tract of the rat as a guideline for their clinical use.

Two spasmolytic drugs, N-butylscopolammonium bromide and octylonium bromide have been challenged against topical carbachol-induced contracture of gastric antrum, duodenum, jejunum, ileum, caecum, colon and rectum of the rat. Experimental data indicate that N-butylscopolammonium bromide, a competitive anticholinergic agent, is more effective on the upper than on the lower sections of the rat gastrointestinal tract. On the other hand octylonium bromide, which has been reported to have little if any competitive antimuscarinic properties at effective spasmolytic doses, showed a more composite spectrum of activity. Hexamethonium, a nicotinic cholinoceptor antagonist, was about equally effective in inhibiting carbachol-induced contractions of all the GIT sections under study. Data in the literature and our own findings do not support the use of competitive antimuscarinic drugs for the treatment of colonic hypermotility. In fact, at effective spasmolytic doses they are expected to produce a greater inhibition of motility of the upper sections of the GIT than at the colonic level.

Animals↗
PubMed1983

Octylonium bromide: a smooth muscle relaxant which interferes with calcium ions mobilization.

A series of "in vitro" experiments have been carried out to determine the mechanisms(s) responsible for the smooth muscle relaxant properties exhibited by octylonium bromide. Unlike N-butyl-scopolammonium bromide, octylonium bromide possesses both competitive and non competitive antimuscarinic and antihistaminic properties. Pretreatment of ileal segments with dibenamie, which destroyed muscarinic spare receptors, revealed the non competitive nature of octylonium bromide antagonism. The competitive antagonism toward BaCl2-induced contraction of rat ileum and aorta suggested that octylonium bromide interferes with Ca++ mobilization. As compared with verapamil a known Ca++ entry blocker and unlike it, octylonium bromide is more effective in antagonizing Ca++-induced contraction in K+ depolarized rat colon than aorta. Both octylonium bromide and verapamil reduced in a concentration-dependent manner the tonic contraction produced by exposure to high K+ of rat duodenum and rabbit ear artery. Both octylonium bromide and verapamil antagonized carbachol-induced phasic plus sustained tonic contraction of rat colon in high K+ Ca++-free medium. Unlike octylonium bromide, verapamil antagonized the phasic contraction only and inhibition of the overall contraction did not exceed 60%. Unlike verapamil, octylonium bromide antagonized norepinephrine-induced contraction of rabbit ear artery in high K+ C++-free medium. Interference with mobilization of cellular and extracellular Ca++ pools produced by different neurohormones is likely to be the mechanism responsible for octylonium bromide smooth muscle relaxant properties in both animals and humans.

Animals↗
PubMed1982

An in vivo procedure for estimating spasmolytic activity in the rat by measuring smooth muscle contractions to topically applied acetylcholine.

An in vivo procedure for evaluating potential organ selectivity of spasmolytics has been developed. This involves the determination of comparative potencies, expressed as DR10 of spasmolytics against contractions induced by topical application of acetylcholine on rat colon, rectum and urinary bladder. Experiments with two well known spasmolytics, namely N-butyl-scopolammonium bromide and dicyclomine HCl yielded results consistent with data reported in the literature. This procedure provides a rapid, inexpensive and rather accurate estimate of organ selectivity of spasmolytics.

Acetylcholine↗
PubMed1982

A simple procedure for assessing norepinephrine-induced cellular and extracellular Ca++ mobilization in rabbit ear artery.

Although the response of vascular smooth muscle to norepinephrine (NE) is biphasic in nature, there is no simple procedure for the separate quantitative analysis of intracellular and extracellular Ca++ dependent NE-induced contractions. Intraluminal NE in high-K+Ca++-free medium produces a dose-dependent contraction which is selectively antagonized by procaine (1 X 10(-3) M--5 X 10(-3) M). Subsequent reperfusion with normal Krebs of NE-pretreated arterial segments results in a dose-dependent contraction which is strictly related to extracellular Ca++ concentration and is selectively inhibited by verapamil (5 X 10(-6) M--5 X 10(-5) M). These results can be interpreted as an indication that this procedure is suitable for the separate analysis of the capability of vasoactive drugs to differentially mobilize cellular and extracellular Ca++ pools in perfused rabbit ear artery preparations.

Animals↗
PubMed1982

Modulation by beta-adrenoreceptors of spontaneous contractions of rat urinary bladder.

1 Propranolol (0.1 mg/kg i.v.) but not metoprolol (0.2 mg/kg i.v.) pretreatment increased the spontaneous motility triggered by progressive filling of rat urinary bladder without a concomitant effect on bladder capacity, except at high filling volumes. Compared to controls, the spontaneous motility of urinary bladder in propranolol pretreated rats displayed a higher frequency, indicating the existence of a tonic sympathetic inhibition. 2 beta-adrenoreceptor stimulation by isoprenaline (0.1-10 microgram/kg i.v.) or terbutaline (0.1-1 mg/kg i.v.) in vivo produced a dose dependent inhibition of bladder spontaneous motility which was antagonized by propranolol (0.1 mg/kg i.v.) but not by metoprolol (0.2 mg/kg i.v.). Propranolol (0.2 mg/kg i.v.) pretreatment did not antagonize the inhibition of bladder motility produced by intravenous papaverine (0.5 mg/kg). 3 Propranolol (0.1 mg/kg i.v.) significantly antagonized the isoprenaline-induced tachycardia (beta 1 mediated) and fall in diastolic blood pressure (beta 2 mediated) while metoprolol (0.2 mg/kg i.v.) antagonism was confined to beta 1 mediated responses. 4 Isoprenaline (0.25-1.5 microM) inhibited in a concentration dependent manner field stimulation induced contractions of rat detrusor muscle strips as did tetrodotoxin (0.5 microM). Hexamethonium (50 microM) had no inhibitory effect. 5 Our in vivo findings support the view that beta 2-adrenoreceptors are responsible for modulating bladder motility mainly by suppressing the onset of spontaneous contractions.

Animals↗