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Biomedical subjects

S Manzini

Publications and source records attributed to S Manzini.

At least 145 records · Page 8Linked to original sources
PubMed1986

Functional and binding evidence of taurine inhibition of alpha-adrenoceptor effects on guinea-pig ventricle.

The effect of taurine on alpha- and beta-mediated positive inotropic effects was investigated in guinea-pig ventricular strips. Loading with taurine dose-dependently antagonized the phenylephrine-induced positive inotropic effect while it was ineffective on beta-mediated positive inotropic effect. The superfusion with a taurine-free medium determined a loss of intracellular taurine, while the loading with 20 mM taurine prevented this depletion. Preincubation of cardiac membranes with different concentrations of taurine (1 to 20 mM) decreased 3H-prazosin binding, and the saturation curve obtained after preincubation of cardiac membranes with 20 mM taurine showed that taurine had a more marked effect on the number of binding sites. In both experimental models, beta-alanine did not mimic any taurine effects, suggesting that taurine actions might be specific.

Animals↗
PubMed1986

An atropine-like inhibitory effect of DMPP on rat isolated urinary bladder.

DMPP inhibits the nerve-mediated contractions of the rat isolated bladder, its effect being greater in preparations from newborn (2 day old) than adult animals. This effect of DMPP was unaffected by hexamethonium. In preparations from adult animals the effect of DMPP increased with frequency of stimulation and was fully prevented by the presence of atropine. In bladders from newborn rats low concentrations of furthrethonium (FHR) (10 nM) activated a series of rhythmic contractions which were unaffected by tetrodotoxin and abolished by DMPP through an hexamethonium-insensitive action. On the other hand DMPP did not affect rhythmic contractions produced by a low concentration of eledoisin (60 nM). In bladders from adult rats FHR (10 microM) and KCI (30 mM) produced contractures of comparable magnitude. DMPP inhibited, in concentration-related manner the FHR-induced tonic contraction but had little effect on that produced by KCI. These findings indicate that in the rat bladder, DMPP antagonizes selectivity cholinergically-mediated contractions through a mechanism which is unaffected by hexamethonium or tetrodotoxin. An "atropine-like' activity of DMPP should be considered.

Aging↗
PubMed1986

5-Hydroxytryptamine delays relaxation time of norepinephrine-induced vasoconstriction.

The effect of low concentration of 5-hydroxytryptamine (5-HT; 0.03-0.3 microM) on cellular and extracellular Ca2+ -dependent norepinephrine (NE; 5 microM)-induced vasoconstriction was assessed in isolated perfused rabbit ear artery. The most remarkable effect of 5-HT is a concentration-dependent enhancement of the duration of the extracellular Ca2+ -dependent NE-induced vasoconstriction. This effect of 5-HT is still present in 6-hydroxydopamine-pretreated arteries and in the presence of deoxycorticosterone and is not mimicked by the K+ channel blocker tetraethylammonium. Administration of nifedipine (0.3 microM) and EDTA (1 mM) failed to antagonize 5-HT-induced prolongation of relaxation kinetics of extracellular Ca2+ -dependent NE-induced vasoconstriction. On the other hand, this phenomenon was abolished by caffeine (15 mM) and markedly reduced by dibutyryl cyclic AMP (3 mM). 5-HT (0.3 microM), but not NE (30-50 nM), enhanced the vasoconstriction elicited by caffeine (15 mM) that was procaine sensitive and unaffected by nifedipine. These results suggest that 5-HT prolonged relaxation kinetics of NE-induced vasoconstriction through an impairment of cellular mechanisms that decrease the myoplasmic level of free Ca2+. A similar mechanism could be of relevance for 5-HT enhancement of vascular smooth muscle responsiveness to vasoactive agents.

Animals↗
PubMed1986

Motor effect of neurokinins on the rat duodenum: evidence for the involvement of substance K and substance P receptors.

The motor effects of kassinin (KAS), substance P (SP) or neurokinin A (NKA) on rat duodenum have been investigated in vivo (urethane anesthesia) or in vitro. Intravenous neurokinins produced a phasic contraction of the duodenum that was unaffected by atropine, hexamethonium or tetrodotoxin. KAS, NKA and SP were almost equieffective in producing this phasic contraction. In addition KAS and NKA (but not SP) induced a tonic contraction with a superimposed series of rhythmic contractions. SP did not produce tonic or rhythmic contractions even in doses producing maximal effects on blood pressure. The KAS-induced tonic and rhythmic contractions were unaffected by atropine or hexamethonium and potentiated markedly by tetrodotoxin. Similar findings were obtained after topical application of neurokinins on the outer surface of the duodenum in vivo or recording the mechanical response of the longitudinal muscle in vitro. The phasic component of the KAS- or SP-induced contraction was reduced selectively, both in vivo and in vitro by [D-Pro2,D-Trp7,9]SP, an SP antagonist. It is concluded that two types of receptors mediate the motor effects of neurokinins in the rat duodenum, one of which is of the SP-P type and is mainly involved in producing the phasic contraction. The other receptor is of the SP-K type and mediates mainly the tonic contraction.

Animals↗
PubMed1985

Further evidence for involvement of adenosine-5'-triphosphate in non-adrenergic non-cholinergic relaxation of the isolated rat duodenum.

The nature of the inhbitory non-adrenergic non-cholinergic (NANC) neurotransmitter responsible for neurogenic relaxation of rat duodenum was studied with in vitro techniques. Adenosine 5'-triphosphate (ATP)(1 mM), gamma-aminobutyric acid (GABA, 1 mM), dimethylphenylpiperazinium (DMPP, 0.1 mM) and field stimulation (60 V, 2 ms, 0.1 Hz) produced transient relaxation followed by rebound contraction. In contrast vasoactive intestinal polypeptide (VIP) (0.3 microM) and noradrenaline (1 microM) induced relaxation which set in more slowly and lasted longer. Tetrodotoxin (0.85 microM) abolished field stimulation-induced relaxation but not ATP-, VIP- or noradrenaline-induced relaxation. Nucleotide pyrophosphatase (0.25 U/ml), but not the proteolytic enzyme alpha-chymotrypsin (2 U/ml), selectively antagonized NANC relaxation. The rank order of potency of various adenine derivatives for inducing relaxation was adenosine-5'-triphosphate greater than adenosine-5'-diphosphate much greater than adenosine greater than adenosine-5'-monophosphate. ATP-induced relaxation was selectively antagonized by the putative P2 purinoceptor antagonist reactive blue 2, but unaffected by the selective P1 purinoceptor antagonist 8-phenyltheophylline. The duration of ATP- as well as beta-gamma-methylene adenosine-5'-triphosphate (a stable analogue of ATP)-induced relaxation was similar and was unaffected by indomethacin 10 microM (which abolished the rebound contraction). In those preparations whose contractile tone was increased by using a high-K+ medium the ability of ATP to elicit relaxation was markedly reduced, while GABA- and DMPP-induced relaxation was abolished. On the other hand, ATP-, GABA- and DMPP-induced relaxation of the tonic component of 5-hydroxytryptamine (5-HT)(0.1 mM)-induced contraction was similar to that observed in control conditions. These findings add further weight to the proposal that endogenous ATP is involved in determining NANC relaxation of rat duodenum.

Adenosine↗
PubMed1985

Contribution of neurogenic and myogenic factors to the contractile activity of the guinea-pig distal colon in vivo and in vitro.

The response of the guinea-pig distal colon to distension and drugs expected to interfere with neural control of contractile activity were investigated in urethane anaesthetized animals and compared to results obtained in the isolated preparation. Under urethane anaesthesia bout 50% of the unloaded preparations had no detectable contractile activity. However these preparations contracted in response to topical acetylcholine. Saline distension induced the appearance of a phasic contractile activity in 'quiescent' preparations and enhanced amplitude of contractions in previously active ones. Atropine (1 mg/kg i.v.) reduced tone and transiently suppressed phasic contractile activity of the distal colon. When phasic contractile activity resumed a second dose of atropine had no further inhibitory effect. Topical physostigmine (20 micrograms in 0.1 ml) produced a marked and long lasting increase in tone paralleled by a marked enhancement in amplitude of the phasic contractile activity. These excitatory effects of topical physostigmine were suppressed by intravenous atropine (1 mg/kg). Hexamethonium (20 mg/kg i.v.) produced a sudden and transient increase in tone and suppressed DMPP (0.1 mg/kg i.v.) but not noradrenaline (2 micrograms/kg i.v.) induced relaxations. Propranolol (2 mg/kg i.v.) or phentolamine (0.5 mg/kg i.v.) transiently increased tone of the guinea-pig distal colon and suppressed noradrenaline induced relaxations. DMPP induced relaxations were reduced by propranolol plus phentolamine. Topical tetrodotoxin (50 micrograms in 0.1 ml) had an overall slight excitatory effect on phasic contractile activity of the in vivo preparation. The effects of i.v. atropine, hexamethonium, phentolamine or propranolol on tone and spontaneous activity were prevented by pretreatment with tetrodotoxin. Isolated segments of guinea-pig distal colon exhibited a fairly regular spontaneous phasic contractile activity whose amplitude was increased by stretching of the preparation. Atropine (3 microM) produced a transient inhibition while hexamethonium (40 microM) had no effect on spontaneous contractile activity. Tetrodotoxin (0.5 microM) had both inhibitory and excitatory effects on tone and spontaneous activity of the preparation. At steady state amplitude of contractions was enhanced (15-30% increase) by tetrodotoxin. DMPP (1-100 microM) first induced a phasic contraction and then suppressed transiently the spontaneous activity of the isolated preparation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

High-cholesterol diet induces altered responsiveness of rabbit arterial smooth muscle to noradrenaline.

The potential effect of feeding a high-cholesterol atherogenic diet (HCD) on in vitro responsiveness of rabbit arterial smooth muscle was investigated. The vasoconstrictor response produced by either exogenous or endogenous (field stimulation) noradrenaline was significantly depressed in isolated segments of ear artery after HCD as compared to regular diet fed animals. On the other hand no changes to high K+ could be observed in arterial segments after HCD as compared to regular diet fed rabbits. In addition, the alpha-adrenoceptor-mediated inotropic response and contraction of bladder smooth muscle showed only minor or no changes after HCD as compared to regular diet fed rabbits.

Adrenergic alpha-Agonists↗
PubMed1985

Regional selectivity of calcium blockers at intestinal level.

Exposure of isolated segments of rat duodenum and proximal colon to either high K+ (55.9 mM) or carbachol (0.1 mM) produced a typical biphasic contraction whose tonic component appears to be almost entirely dependent upon the presence of extracellular Ca++. Verapamil and nifedipine suppressed high K+-and carbachol-induced tonic contractions of both duodenum and proximal colon but a large component of carbachol-induced contraction of proximal colon was insensitive to these substances. Verapamil and nifedipine were: a. 5 and 3 times more effective in antagonizing high K+-induced tonic contractions in the rat duodenum than in the proximal colon, respectively, and b. 10 and 4 times more effective in antagonizing high K+ than carbachol induced tonic contractions of rat duodenum, respectively. The verapamil- or nifedipine- resistant component of carbachol induced tonic contraction of proximal colon was suppressed by drugs which, like octylonium bromide and urethane, have been shown to interfere with mobilization of Ca++ from intracellular storage sites. Experiments in Ca++-free medium indicate the existence in the proximal colon of a significant intracellular Ca++ store which could be mobilized during carbachol but not high K+-induced tonic contractions. These findings indicate that, in the rat intestine, significant regional differences exists in Ca++ pools mobilized by different activating stimuli and in sensitivity to the blocking action of drugs which interfere with Ca++ mobilization from either intra- or extracellular Ca++ pools.

Animals↗
PubMed1985

Inhibitory effect of GABA on sympathetic neurotransmission in rabbit ear artery.

GABA 100 microM inhibited neurogenic vasoconstrictor responses elicited in rabbit ear artery by field stimulation at various frequencies. GABA was ineffective both on resting tone and on noradrenaline (0.05-5 microM)- and high-K+ (24-54 mM)-induced tonic contraction. GABA effectiveness against field stimulation-induced vasoconstriction was inversely related to the frequency of stimulation. This action of GABA was mimicked by a selective GABAB agonist, such as baclofen (100 microM), but not by selective GABAA agonists as muscimol (100 microM) and homotaurine (100 microM). The selective GABAB antagonists 5-aminovaleric acid (1 mM) and homotaurine (100 microM) completely suppressed the inhibitory effect of GABA on field stimulation-induced vasoconstrictions. GABA action was partially reversed also by the selective GABAA antagonist picrotoxin (100 microM); however, this drug "per se" determined an increase in amplitude of field stimulation-induced contractions which in turn could have determined the minor effect of GABA. As a whole these data suggest that GABA can inhibit sympathetic neurotransmission in rabbit ear artery through the stimulation of a prejunctional receptor of the GABAB subtype.

Amino Acids↗
PubMed1984

An analysis of the effects of urethane on cardiovascular responsiveness to catecholamines in terms of its interference with Ca++ mobilization from both intra and extracellular pools.

Urethane (1 X 10(-2) - 1 X 10(-1) M) reduced, in a concentration-dependent manner, both intra and extracellular Ca++ dependent noradrenaline-induced contractions of perfused rabbit ear artery as well as the tonic contractions produced by perfusion with high K+ solution. However, a quantitative analysis of the data indicated that for urethane concentrations similar to those found in plasma during anesthesia urethane antagonism is confined to noradrenaline-induced contractions which depend upon the mobilization of Ca++ from intracellular storage sites. In KCl-contracted arteries, urethane enhanced the relaxant effects of isoprenaline. - Urethane reduced the amplitude of contractions of spontaneously beating guinea-pig right atrium at concentrations which have only a limited effect on frequency. In addition, it decreased in a concentration-dependent manner the amplitude of isoprenaline-activated electrically driven, and K+ depolarized guinea-pig right ventricular strips. Urethane had no effect on the chrono and inotropic actions of isoprenaline on cardiac preparations. In in vivo experiments the chronotropic response to low doses of isoprenaline was significantly higher in urethane-treated as compared to unanesthetized rats. The higher dose of isoprenaline tested produced a significant fall in systolic blood pressure in urethane-anesthetized rats. A significant correlation exists between the chronotropic response to isoprenaline and resting heart rate values in urethane-anesthetized rats. These results indicate that urethane, at concentrations similar to those found in plasma during anesthesia selectively interferes with mobilization of Ca++ from intracellular storage sites. In addition, the interference of urethane anesthesia with the isoprenaline chronotropic effect 'in vivo' cannot be explained by a direct interference of urethane with beta-adrenoceptors at cardiac level.

Animals↗
PubMed1984

Evidence that GABAA receptors mediate relaxation of rat duodenum by activating intramural nonadrenergic-noncholinergic neurones.

GABA produced rapid and transient relaxation of rat duodenum. Homotaurine (3-aminopropansulphonic acid) but not (+/-)-baclofen had a GABA-like effect. GABA-induced relaxation was almost completely inhibited by tetrodotoxin but was unaffected by atropine. Cross desensitization developed between GABA and homotaurine but not between GABA and (+/-)-baclofen. The concentration response curve to the relaxant effects of GABA was shifted to the right by both bicuculline and picrotoxin. However maximal relaxation was still produced by GABA in the presence of bicuculline but not in the presence of picrotoxin. GABA-induced relaxation was not affected by prazosin, yohimbine, propranolol or reserpine pretreatment. Field stimulation (0.1 Hz) of rat isolated duodenum in the presence of atropine and guanethidine produced relaxation similar to that produced by GABA. The ganglionic stimulant DMPP produced a similar effect. Neither Met-enkephalin, noradrenaline, 5-HT, histamine, VIP or arachidonic acid could be held responsible for GABA-induced neurogenic relaxation of rat duodenum. ATP produced relaxations which closely mimicked those produced by either GABA or field stimulation. Exposure to ATP desensitized responses to both GABA and field stimulation to about the same extent. ATP, GABA and field stimulation-induced relaxation was unaffected by either theophylline or indomethacin, but was significantly and selectively antagonized by apamin. In conclusion, GABA-induced relaxation of rat isolated duodenum is largely dependent upon activation of intra-mural nonadrenergic-noncholinergic neurones. The GABA receptor involved appears to be of the GABAA subtype. Circumstantial evidence is provided indicating that ATP might be the endogenous substance released by GABA.

Animals↗
PubMed1984

Differential effects of vasodilators on the mobilization of calcium pools during contractions of rabbit ear artery induced by noradrenaline and high potassium.

The effects of some vasodilators on the mobilization of different Ca2+ pools during contractions produced by noradrenaline and high K+ medium in rabbit ear artery has been investigated. Sodium nitrite was much more effective in antagonizing high K+-stimulated Ca2+ fluxes through the potential-dependent Ca2+ channels than noradrenaline-induced mobilization of intracellular Ca2+ stores or Ca2+ fluxes through receptor-operated channels. Papaverine was only slightly more active on contractions sustained by influx of extracellular Ca2+ (through potential-dependent channels and receptor-operated channels) than on those sustained by intracellular Ca2+. Verapamil and nifedipine were much more effective in antagonizing contractions sustained by Ca2+ entry through potential-dependent channels than through receptor-operated channels. Nifedipine was completely ineffective in antagonizing noradrenaline-induced mobilization of intracellular Ca2+ stores while verapamil had a limited inhibitory action in high concentrations. Phentolamine was equieffective in antagonizing both types of noradrenaline-induced contractions while having no effect on high K+-induced tonic contraction.

Animals↗
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

Differences between the effects of phenylephrine and other inotropic interventions on post-rest contraction in guinea-pig ventricular strips.

The influence of several inotropic interventions on the strength of the post-rest contraction (PCR) was studied in isolated guinea-pig ventricular strips. In preparations stimulated at 1 Hz and incubated in 3.6 mM Ca++, the PRC-maximum potentiation was obtained after a rest interval of 2 sec (optimum resting time: ORT); a post-rest potentiation was present until 15 sec of rest. An increase in stimulation rate and in Ca++ concentration induced a shift in the ORT towards 15-20 sec, and an increase in the potentiation of PRC. At a low stimulation rate (0.33 Hz) the PRC was lower than steady-state contraction (SSC) at all rest intervals tested. Phenylephrine (5 X 10(-6) M) did not modify the ORT either at 1 or 2.5 Hz, and reduced the height of PRC at 0.33, 1 and 2.5 Hz. These results are discussed in terms of the different effects induced by the various inotropic interventions on cellular calcium availability.

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

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↗