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Biomedical subjects

A Meli

Publications and source records attributed to A Meli.

At least 181 records · Page 10Linked to original sources
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

Differences in cardiovascular responses to peripherally administered GABA as influenced by basal conditions and type of anaesthesia.

The cardiovascular (blood pressure, heart rate, cardiac contractility) effects of i.v. gamma-aminobutyric acid (GABA) were investigated in guinea-pigs anaesthetized with barbitone or urethane. GABA (0.1-10 mg kg-1) produced a transient 'depressive' effect on cardiovascular parameters which in barbitone-anaesthetized animals was followed by a transient 'excitatory' effect. Resting cardiovascular parameters were higher in urethane-as compared to barbitone-anaesthetized animals. Picrotoxin pretreatment (2 mg kg-1, i.v.) barely affected the cardiovascular changes produced by GABA in barbitone-anaesthetized animals. In picrotoxin pretreated animals anaesthetized with urethane, GABA produced an initial depression of cardiovascular parameters followed by an excitatory phase. Hexamethonium (20 mg kg-1, i.v.) suppressed or reduced markedly the GABA-induced cardiovascular changes both in barbitone- or urethane- anaesthetized animals. Reserpine pretreatment lowered resting cardiovascular parameters. In these animals, regardless of type of anaesthesia, the effects of i.v. GABA were of the 'excitatory' type only. Reserpine pretreated animals anaesthetized with barbitone were selected for further experiments. Various GABAA receptor agonists (homotaurine, muscimol, THIP, 5-aminovaleric acid) mimicked the 'excitatory' effect of GABA in reserpine pretreated animals anesthetized with barbitone and prevented the effects of subsequent GABA administration. On the other hand (+/-)-baclofen, a selective GABAB receptor agonist, had a slight depressant effect and did not prevent the 'excitatory' cardiovascular effects of GABA. Neither bicuculline nor picrotoxin pretreatment prevented the 'excitatory' cardiovascular effect of i.v. GABA in reserpine pretreated, guinea-pigs anaesthetized with barbitone. In adrenalectomized guinea-pigs or in preparations receiving i.v. phentolamine plus propranolol, GABA produced only a small 'depressant' effect on cardiovascular parameters. These findings demonstrate that GABA exerts a neuromodulatory effect on cardiovascular function via peripheral actions which is influenced by: type of anaesthesia resting values of cardiovascular parameters degree of activity of the sympathetic nervous system and catecholamine release from the adrenal medulla.

Adrenal Medulla↗
PubMed1986

Functional evidence for altered activity of GABAergic receptors following chronic desipramine treatment in rats.

The antinociceptive effect of subcutaneous 4,5,6,7-tetrahydroisoxazol[5,4-c]pyridin-3-ol (THIP) or (+/-)-baclofen, measured as reaction time of rats placed on a plate heated to 55 degrees C, was assessed after a single or the last repeated (18 consecutive days) dose (5 mg kg-1 once daily) of subcutaneous desipramine. Baclofen (10 mg kg-1)-induced antinociception was reduced by acute and unaffected by chronic desipramine treatment. On the contrary, THIP (20 mg kg-1)-induced antinociception was unaffected by acute and reduced by chronic desipramine.

Analgesics↗
PubMed1986

Functional evidence for the existence of a capsaicin-sensitive innervation in the rat urinary bladder.

Capsaicin (0.03-3 microM) induces contractions of the rat isolated bladder which are unaffected by either atropine (3 microM) or tetrodotoxin (0.5 microM). In the presence of capsaicin (0.1 microM) an enhancement of field stimulation-induced contractions was observed. Capsaicin-desensitization did not modify the height of these. The neurogenic nature of the capsaicin-induced contractions was proved by the observation that 'chronic' (48 h) denervation prevented, while 'acute' (2 h) denervation did not modify the effect of capsaicin. Denervated bladders maintained their responsiveness to acetylcholine but not to field stimulation. Isolated bladders from rat pups (1-2 days old) did not respond to capsaicin while strong contractile responses to acetylcholine or field stimulation were obtained in these preparations. In bladders from two week old animals, capsaicin produced similar contractions to those observed in preparations from adult animals. The bladders from rats receiving a high dose of capsaicin (50 mg kg-1 s.c.) at birth were heavier than those of their age-matched, vehicle-treated controls. Isolated bladders from 2 month old animals pretreated with capsaicin at birth were unresponsive to capsaicin while responsiveness to acetylcholine, substance P or field stimulation was unaffected compared with that of vehicle-treated controls. These experiments provide evidence that a capsaicin-sensitive innervation exists in the rat urinary bladder which undergoes a postnatal development at end organ level.

Animals↗
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

Postnatal development of micturition reflex in rats.

The postnatal development of the micturition reflex and factors related to its initiation have been investigated by means of cystometric techniques under urethan anesthesia. In rats less than 10 days of age, micturition is not elicited in response to bladder distension. In these animals voiding is triggered by application of a somatic stimulus in the perineal area. In rats greater than or equal to 15 days of age the response to bladder filling is similar to that observed in adults. In rats 10-15 days of age an intermediate pattern is frequently observed; i.e., bladder filling elicited micturition at high values of pressure threshold. The myogenic (tetrodotoxin insensitive) contractile activity of the bladder is absent at birth and developed postnatally, similar to that described in the isolated organ [C. A. Maggi, P. Santicioli, and A. Meli. Am. J. Physiol. 247 (Regulatory Integrative Comp. Physiol. 16): R972-R978, 1985]. The ability of topical capsaicin to induce tetrodotoxin-sensitive contractions of rat bladder (micturition reflex) appeared at day 10 and increases thereafter in parallel with ability of the bladder to respond to distension. These findings demonstrate that peripheral factors, such as myogenic contractile activity and sensory innervation, which are involved in the initiation of bladder voiding undergo a postnatal development in rats.

Administration, Topical↗
PubMed1986

Analysis of factors involved in determining urinary bladder voiding cycle in urethan-anesthetized rats.

The mechanism(s) involved in determining the voiding cycle of the rat urinary bladder have been investigated in urethan-anesthetized animals. Fluid emission is almost confined to that phase of the voiding cycle which is characterized by the presence of a series of high-frequency oscillations in intraluminal pressure (IPHFO). During this phase the mean urethral flow rate reached a maximum and fluid was expelled in a stream-like fashion. The index obtained by multiplying the amplitude of IPHFO by their duration was significantly related to the maximal value of urethral flow rate. The IPHFO were selectively abolished by administration of d-tubocurarine at a dose that barely affects detrusor contractility. Moreover, d-tubocurarine reduced mean urethral flow rate and increased residual volume. The reflex (hexamethonium sensitive) mechanism(s) responsible for the generation of IPHFO is more developed in male than female rats. This mechanism, which involves activation of skeletal muscle, plays a significant role in determining bladder voiding in this species.

Anesthesia↗
PubMed1986

Rociverine citrate: a new spasmolytic agent, potentially useful in the treatment of urinary bladder hyperreflexia.

Rociverine citrate was evaluated for its ability to affect the motility of rat urinary bladder, in vitro and in vivo, in comparison with flavoxate hydrochloride. Rociverine counteracted both methacholine- and high K+-induced tonic contractions of bladder strips. In anaesthetized rats, intravenous rociverine inhibited dose-dependently frequency and amplitude of the distension-induced rhythmic contractions (DIRCs) of urinary bladder and counteracted the topical high K+-induced pressure increase in the same organ. Orally administered rociverine produced a dose-related reversal of the reserpine-induced detrusor hyperreflexia in anaesthetized rats. In each of these experimental models rociverine was more effective than flavoxate. These results point to the usefulness of rociverine in the treatment of urinary bladder motility disorders.

Animals↗
PubMed1986

Activation of micturition reflex by substance P and substance K: indirect evidence for the existence of multiple tachykinin receptors in the rat urinary bladder.

The ability of substance P (SP) and substance K (SK) to activate motility of the rat urinary bladder "in vivo" and "in vitro" have been compared. In urethane-anesthetized rats topical application of tachykinins on the serosal surface of the bladder elicited a series of neurogenic rhythmic contractions (micturition reflex). SK is about 13.5 times more potent than SP. The extent of the effects of both SP and SK depends on the bladder initial volume. SP and SK are equally effective in: contracting the tetrodotoxin-pretreated rat bladder in vivo; contracting the isolated rat bladder in vitro; enhancing the contractions induced by field stimulation; and delaying relaxation of bladder muscle in response to stretch. These findings suggest the existence of two different sites (receptors) for tachykinins in the rat bladder whose activation is responsible for initiation of the micturition reflex and direct smooth muscle contraction, respectively. The higher potency of SK, as compared to SP, in activating the micturition reflex suggests the involvement of a receptor of the SP-E type, possibly located on the afferent nerve endings, in the mediation of this type of response. The other receptor, located on the smooth muscle cell (and possibly on the efferent nerve endings) appears to be of the SP-P type, as it is equally sensitive to the two tachykinins.

Administration, Topical↗
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

Comparison of the effects of substance P and substance K on blood pressure, salivation and urinary bladder motility in urethane-anaesthetized rats.

The effects of substance P and substance K on blood pressure, salivation and urinary bladder motility were investigated in urethane-anaesthetized rats. On intravenous administration, both peptides produced dose-related reductions in blood pressure, substance P being 25-30 times more potent than substance K. Substance P induced a dose-dependent increase of salivation, while substance K was half as active and induced only 40% of the maximum effect of substance P. The two tachykinins induced contractions of the urinary bladder, substance K being about twice as effective as substance P. Substance K was more effective than substance P in activating micturition. These findings provide further evidence that multiple receptor types are involved in mediating the effects of tachykinins in peripheral organs.

Anesthesia↗
PubMed1985

Influence of antioxidants and radical scavengers on ethanol-induced gastric ulcers in the rat.

Sodium benzoate in doses which do not possess antisecretory properties, produced a dose-dependent reduction of ethanol-induced gastric lesions in the rat. Indomethacin pretreatment antagonized sodium benzoate-ulcer reducing properties indicating that this latter acts, at least in part, through stimulation of prostaglandins synthesis. Propyl gallate reduced ethanol-induced gastric lesions in doses which exert antisecretory properties.

Animals↗
PubMed1985

The effect of peripherally administered GABA on noradrenaline-induced reflex vagal bradycardia in urethane anaesthetized rats.

Intravenously administered GABA significantly reduced the size of noradrenaline-induced reflex vagal bradycardia without affecting blood pressure increase. Intravenously administered GABA reduced bradycardia elicited by stimulation of preganglionic fibres in the vagus nerve. These findings provide evidence suggesting that, in addition to its well known effects on structures regulation cardiovascular function at CNS level GABA could modulate baroreceptor reflex(es) by acting at a peripheral site.

Anesthesia↗
PubMed1985

The effect of cyclooxygenase inhibitors on the low filling rate cystometrogram in urethane anesthetized rats.

The effect of two widely used cyclooxygenase inhibitors (indomethacin and ketoprofen) on the low filling rate cystometrogram was investigated in urethane anesthetized rats. Both indomethacin and ketoprofen significantly increased volume threshold to elicit neurogenic bladder contractions without affecting their amplitude. Also the pressure threshold was unaffected by both drugs while the volume/pressure relationship was significantly flattened compared to controls. These findings indicate that acute suppression of arachidonic acid metabolism along the cyclooxygenase pathway increases the micturition threshold without affecting bladder muscle contractility and/or neurotransmission along the efferent pathway of the micturition reflex.

Anesthesia↗
PubMed1985

The effect of capsaicin pretreatment on the cystometrograms of urethane anesthetized rats.

Administration of capsaicin to newborn rats produced a slight but significant increase in bladder weight and markedly altered the cystometrograms of urethane anesthetized rats. In particular capsaicin pretreatment significantly increase micturition threshold. In many of these preparations the bladders exhibited a hypertonic response to saline filling; the flat phase of the cystometrogram was not observed. Capsaicin pretreatment of adult animals increased micturition threshold up to 1 month from capsaicin administration. In these preparations a flat volume-pressure relationship preceded micturition contractions. Administration of capsaicin to both newborn and adult animals did not alter the amplitude of micturition contractions. Intravesical installation of capsaicin had an acute excitatory effect on the responsiveness of the urinary bladder to reflex activation. These findings indicate that capsaicin pretreatment produces a functional impairment of the sensory branch of micturition reflexes and suggest that a capsaicin-sensitive mechanism(s) is involved in the regulation of micturition threshold.

Anesthesia, General↗