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PubMed1981

Effects of reserpinization, surgical denervation and in vitro chemical denervation with 6-hydroxydopamine on the contractile response of isolated rabbit ear artery to propranolol.

The contractile effect of propranolol in isolated rabbit ear artery was assessed in reserpinized and in surgically and chemically denervated blood vessels. Reserpinization and surgical denervation either had no effect on or enhanced the ear artery contractile response to 10(-6) to 10(-4) M propranolol. In contrast, the contractile response to propranolol was nearly abolished after denervation of the ear artery in vitro with 6-hydroxydopamine (6-OHDA). Dose-response curves to norepinephrine were shifted to the left by factors of 4.9 in 6-OHDA denervated ear arteries and 15.6 in untreated arteries in the presence of 10(-7) M desipramine. The diluent for 6-OHDA shifted both the norepinephrine and propranolol dose-response curves to the right. It is proposed that propranolol caused a contractile response in ear artery by an action on the postsynaptic tissues of this vessel. 6-OHDA denervation caused nonspecific desensitization in rabbit ear artery leading to the loss of response of this vessel to propranolol.

Animals↗
PubMed1976

Effects of various drugs supposed to interact with serotonin on PGO frequency changes induced by reserpine and 5-hydroxytryptophan.

Reserpine induced ponto-geniculo-occipital (PGO) spikes in the lateral geniculate nucleus. This was used as a model to evaluate the possible anti-reserpine effects of Org GB 94-1,2,3,4,10,14b-hexahydro-2-methyldibenzo[c,f]pyrazino [1,2-alpha]azepine monohydrochloride-methiothepin, imipramine and atropine. In cats, under local anaesthesia, 3.2 mg/kg of methiothepin (a serotonin antagonist and neuroleptic) increased PGO density while 5-hydroxytryptophan (5-HTP) effects were blocked. A dose of 0.32 mg/kg of imipramine or atropine greatly reduced PGO density while potentiating 5-HTP effects. Org GB 94 had no effect in doses up to 10 mg/kg, where a slight decrease of PGO density was found, while 5-HTP effects were unchanged. At 32 mg/kg, EEG was pronouncedly changed by Org GB 94 but only a short-lasting decrease in PGO density was noted. On the basis of these results it seems improbable that the behavioural effects of Org GB 94 are to be explained by the same mechanism (i.e. serotonin uptake inhibition) as that of imipramine.

5-Hydroxytryptophan↗
PubMed1981

Influence of phenothiazines or reserpine on the formation of 14C-glycine from U-14C-serine.

The influence of the psychopharmaceuticals reserpine, thioproperazine and chlorpromazine on the synthesis of 14C-glycine from U-14C-serine was examined in a rat brain preparation. At low serine concentration (2 times 10(-5) mol/l) glycine synthesis in inhibited by all drugs tested probably due to the inhibition of the serine influx into mitochondria. At higher concentration (10(-3) mol/l) and physiological cofactor levels, phenothiazines increase to the measurable amount of 14C-glycine while reserpine has no effect. We assume that at this higher concentration serine transport through the mitochondrial membranes is no longer rate limiting; following phenothiazine action, the membrane-bound glycine cleavage system might be inhibited more strongly than the partly soluble serine hydroxymethyltransferase.

Animals↗
PubMed1979

Lithium plus reserpine in refractory manic patients.

The authors report on six refractory manic or schizo-affective manic male outpatients who failed to respond to lithium combined with a neuroleptic. A beneficial response was noted in most patients when reserpine was substituted for their currently prescribed standard neuroleptic; in some cases lithium dosage could then be reduced. No major side effects were encountered. The use of reserpine may offer an alternative mode of therapy for manic patients who cannot tolerate large doses of lithium or do not completely respond to lithium either alone or in combination with a standard neuroleptic.

Adult↗
PubMed1975

The chronically reserpinized rat as a possible model for cystic fibrosis. II. Comparison and cilioinhibitory effects of submaxillary saliva.

Submaxillary saliva from reserpine-treated rats was found to have alterations in composition similar to those reported in the same secretion from patients with cystic fibrosis. Changes included elevated concentrations of Na+, Ca++, protein, and carbohydrate. In addition, this saliva was found to have ciliotoxic properties similar to those of CF serum. The similarities in cilioinhibitory effects salivary composition, and histologic appearance justify the use of the chronically reserpinized rat as a model for cystic fibrosis.

Animals↗
PubMed1976

The chronically reserpinized rat as a possible animal model for cystic fibrosis. IV. The protein composition of pulmonary lavage fluid.

Lung lavage samples obtained from patients with cystic fibrosis (CF) had significantly higher levels of total protein per ml lavage fluid (0.49 vs. 0.30 mg/ml). A significant increase in the absolute and relative amounts of a low molecular weight glycoprotein (15,000 mol wt) was noted in lavage specimens from CF patients. Reserpine-treated rats also showed a significant increase in the total protein recovered in the lung lavage fluid with a 233% increase in the absolute and relative amounts of a low molecular weight glycoprotein (15,000 mol wt). Thus, reserpine induced changes in the secretions of the lung of the rat which are similar to those observed in samples obtained from the lung of CF patients.

Adult↗
PubMed1984

Pulmonary function of the reserpine and isoproterenol models of cystic fibrosis.

Two experimental animal models exhibiting functional and morphologic changes of exocrine glands similar to those seen in patients with cystic fibrosis (CF) have been reported in the rat: chronic stimulation with reserpine (Martinez et al. 1973 Pediatr. Res. 9:463, 470) and chronic stimulation with isoprenaline (Sturgess and Reid 1973 Br. J. Exp. Pathol. 54:388). We have studied the pulmonary function of these models induced by injecting rats subcutaneously with reserpine (RES, 0.5 mg/kg/day), isoproterenol (ISO, 25 mg/kg/day), or saline (Con, 1.0 ml/kg/day) for 6 days. Plethysmographic measurements were made for functional residual capacity (FRC), airways resistance (Raw), specific airways conductance (sGaw), phase difference between air flow rate and mean alveolar pressure (PD), frequency of breathing (f), and tidal volume (VT) of the anesthetized rats. In the RES and ISO rats, the FRC, Raw and f were not different from Con values. The PD was greater and the VT was less than Con values (p less than 0.05). The results of both studies indicate uneven ventilation (increased PD) and penduluft (decreased VT) consistent with maldistribution of resistance and/or compliances of the peripheral airways and/or alveolar compartments. These physiologic effects can be related to the morphologic changes reported for the airways of rats under chronic adrenergic stimulation (ISO) and expected for rats under chronic catecholamines depletion (RES). Since peripheral airways involvement is usually the earliest pulmonary lesion found in CF, these studies indicate that the RES and ISO models may be representative of the early pulmonary involvement of CF.

Airway Resistance↗
PubMed1976

Influence of reserpine on high calcium perfusion of thyro-parathyroid glands in dogs.

Perfusion of the thyro-parathyroid glands in the dog with calcium-rich blood led to a significant decrease (P less than 0.001) in the systemic plasma calcium level. On the other hand, injection of reserpine (0.2 mg/kg ip) 16 and 2 h prior to infusion of hypercalcemic blood into thyro-parathyroid glands did not alter the systemic plasma calcium level significantly (P less than 0.05). This result provides evidence that reserpine blocks the release of hypocalcemic factor from the thyro-parathyroid glands in response to perfusion of high concentrations of calcium.

Animals↗
PubMed1984

Effect of reserpine-kanamycin treatment on chronic vasospasm after platelet-enriched subarachnoid hemorrhage in primates.

A model of chronic cerebral vasospasm (VSP) analogous to the clinical situation was established by inducing subarachnoid hemorrhage (SAH) in monkeys. Platelets harvested from 4 ml of blood were added to autologous blood in an attempt to accentuate any effect that vasoactive substances such as serotonin, contained in platelets, might have on producing cerebral VSP. Antiserotonin medications were administered in an attempt to reduce the frequency or severity of angiographically proven VSP. Animals were divided into small (1 ml/kg) and large (1.2 to 1.5 ml/kg) hemorrhage groups and later were randomized equally to receive either saline placebo or reserpine (0.013 mg/kg i.m.) and kanamycin (50 mg/kg p.o.) administered 3 hours after SAH and daily thereafter to Day 7. In both the small and the large hemorrhage groups of treated animals, there was a significant reduction in serotonin levels (P less than 0.01 and P less than 0.05, respectively) compared to base line levels. In the groups of nontreated monkeys with small and large hemorrhages, serotonin levels were not statistically different from control values. Despite reduction of serotonin levels to 19 and 26% of the control values in the small and large hemorrhage, treated groups, there was no apparent difference in the frequency or severity of angiographically proven VSP. This study found no evidence that reserpine and kanamycin have a beneficial effect on preventing VSP when treatment is begun after SAH.

Animals↗
PubMed1979

Effects of intraventricularly administered serotonin, noradrenaline, dopamine and metaraminol on the reserpine-induced spikes recorded from the medial nucleus trapezoides in rabbits.

Effects of intraventricularly administered serotonin (5HT), noradrenaline (NA), dopamine (DA) and metaraminol on the reserpine-induced spikes recorded from the medial nucleus Trapezoides (Trap. m.) in rabbits were investigated. 5HT (30, 50 micrograms) produced marked decreases in the amplitude and discharge rate of the spikes 3 to 5 min after intraventricular administration. NA (30, 50 micrograms) also produced similar effects to those of 5HT, but DA at the same dosage produced no significant changes in the amplitude and discharge rate of spikes. Metaraminol, a metabolite of alpha-methyl-m-tyrosine, produced gradual and long-lasting, potent suppression of spikes. Ninety min later, spikes were completely suppressed, and no recovery was observed within 6 hours after intraventricular administration. These results indicate that NA has a similar suppressing action to that of 5HT on the generation of the reserpine-induced spikes.

Action Potentials↗
PubMed1983

Effects of reserpine, alpha-methyl-p-tyrosine, p-chlorophenylalanine and 5,7-dihydroxytryptamine on the hippocampal kindling effect in rats.

The role of the brain monoamines in the development of hippocampal kindling was studied. Reserpine markedly facilitated the formation of hippocampal kindling. The high amplitude spike waves in the amygdala and reticular formation appeared earlier in the reserpine treated rats than in the saline injected rats. alpha-Methyl-p-tyrosine did not have any effect on the formation of hippocampal kindling. Systemic injection of p-chlorophenylalanine and intraventricular injection of 5,7-dihydroxytryptamine also did not have any effect on the formation of hippocampal kindling. Progressive changes of afterdischarge elicited by hippocampal stimulation in the alpha-methyl-p-tyrosine, p-chlorophenylalanine and 5,7-dihydroxytryptamine treated rats are the same as those in the saline injected rats. These results indicate that the decrease in both catecholamines and serotonin levels caused a marked facilitation of the hippocampal kindling formation, but the separate decrease in either catecholamines or serotonin did not produce a significant effect.

5,7-Dihydroxytryptamine↗
PubMed2001

Release of dopamine and ATP from PC12 cells treated with dexamethasone, reserpine and bafilomycin A1.

The amounts and time courses of dopamine and ATP released from perfused PC12 cells were examined using a simultaneous on-line recording system. High KCl (60 mM) caused dopamine and ATP release with similar time courses. The relative amount of dopamine to ATP in the effluent was 9.5. In PC12 cells cultured with dexamethasone, reserpine or bafilomycin A1 for 2 days, these drugs did not affect increases of intracellular Ca2+ in response to high KCl. Dexamethasone doubled the amount of dopamine release induced by high KCl without changing the amount of ATP release. High KCl failed to cause dopamine release in reserpine-treated cells but evoked ATP release. Bafilomycin A1 decreased both high KCl-induced dopamine and ATP release. The ratio of released ATP to total adenine nucleotides and adenosine in response to high KCl was not changed by treatment with the drugs. These results suggest that dopamine and ATP are simultaneously released from secretory vesicles of PC12 cells, in which they are stored via different pathways. Similar to dopamine uptake into secretory vesicles, the H+-gradient across the vesicular membrane developed by vacuolar ATPase may play an important role in the vesicular uptake of ATP.

Adenosine Triphosphate↗
PubMed1980

Variability in neurosecretory material and responses to reserpine of the pituitary neural lobe in five strains of rat.

The levels of vasopressin and neurophysin in the neural lobe of the pituitary were measured in five strains of rat: Wistar, Sprague-Dawley, PVG, Chester Beatty and DA strains. The effect of reserpine administration (5 mg/kg body weight) was determined. There were significant differences in the weight of the neural lobe and the vasopressin and neurophysin contents of this tissue in the various strains. It was possible to show that weight of the neural lobe was not necessarily related to hormone content. The effects of reserpine also varied within the species for, while there was a fall in the vasopressin content in the Wistar and Chester Beatty strains, no change was observed in the Sprague-Dawley, PVG and DA strains. The fall in the vasopressin level in the Wistar animals was not accompanied by a simultaneous fall in the vasopressin-neurophysin content.

Animals↗
PubMedDate not supplied

Effects of reserpinization on the electrolytes distribution in inner ear fluids of guinea pig.

Reserpine (2 mg/kg and 10 mg/kg, i.p.), an adrenergic blocker, was administered to normal guinea pigs, and samples of serum, CSF, scala tympani perilymph, scala vestibuli perilymph and cochlear endolymph were collected. The concentrations of Na and K in these fluids were then assessed to observe electrolyte distributions. Both Na and K concentrations were reduced in serum. In CSF, the Na concentration was markedly depressed, while the K concentration remained unchanged. Scala tympani perilymph showed a pattern of electrolyte changes similar to that in CSF. In scala vestibuli perilymph, the Na concentration was unaltered, but the K concentration was lowered. Cochlear endolymph exhibited no change of the Na concentration but there was a marked decrease in the K concentration. These changes are thought to be attributable to the indirect blockage of energy producing systems in membrane transport in the inner ear by the reserpine-induced depletion of catecholamines.

Animals↗
PubMed1989

Attenuation of reserpine-induced catalepsy by melatonin and the role of the opioid system.

Several reports have indicated that melatonin influences motor activity in animals and humans. Melatonin has been reported to attenuate the rigidity and tremor of Parkinson's disease. Some of the behavioral effects (e.g., analgesic and anticonvulsant properties) of melatonin have been reported to be mediated through interactions with the endogenous opioid peptides. We investigated the effect of melatonin on reserpine-induced catalepsy in the rat and, additionally, examined whether this effect is modified by opioid peptides. Melatonin was found to attenuate markedly the duration of reserpine-induced catalepsy. These effects were potentiated by administration of the opiate agonist nalbuphine hydrochloride, while naloxone partially reversed the catalepsy reducing effect of melatonin. These findings suggest that the motor effects of melatonin may involve critical interactions with opioid peptides, and support the postulated reciprocal interactions between melatonin and opioid peptides that previously have been demonstrated for the analgesic and anticonvulsant properties of melatonin.

Animals↗
PubMed1985

Developmental status of sympathetic innervation in relation to calcium accumulation by submandibular gland following reserpine, surgical sympathectomy or cyclocytidine.

Sympathectomy (Sx) of the submandibular gland was induced at various postnatal ages by ip administration of a single dose of reserpine or by unilateral excision of a superior cervical ganglion. If animals were 12 days old or less at the time of drug administration, [Ca] of the submandibular gland was not measurably increased 24 hr later; if rats were 14 days of age or older, [Ca] of the gland 24 hr after reserpine injection was nearly double that of untreated controls. Two days after surgical Sx, [Ca] of the denervated submandibular gland was unchanged from that of the innervated member of a pair if animals were less than 14 days of age at the time of denervation; [Ca] was twice that of glands of control rats if animals were older than 14 days of age when the denervation was performed. The anti-tumor agent, cyclocytidine (CC), given daily for 3 days in an ip dose of 500 mg/kg, also caused a two- to threefold increase in [Ca] of the submandibular gland when rats were more than 12 days of age at the time of the initial injection of the drug, but in rats younger than this age, CC caused no change in the [Ca] of the submandibular gland. Present data show that there are age-related differences in the ability of the submandibular gland to accumulate calcium following sympathetic denervation or treatment with a norepinephrine-releasing drug. These differences may be attributed either to incomplete development of calcium transport mechanisms, or incomplete development of the sympathetic innervation before 14 days of age.

Age Factors↗
PubMed1988

The effects of reserpine upon the cardiac enlargement of copper deficiency.

Copper (Cu) deficiency, induced in rats by suckling from Cu-deficient dams and by offering a semisynthetic low-Cu diet from weaning, resulted in cardiac enlargement. This enlargement was not due to accumulation of excess fluid in the heart but was characterized by mitochondrial hypertrophy as demonstrated by electron microscopy and biochemical studies. Administration of reserpine limited the extent of cardiac enlargement; however, heart total noradrenaline (NA), unchanged by Cu deficiency, was significantly reduced by reserpine. It was concluded that cardiac enlargement in Cu deficiency was not directly related to NA concentration. An alteration in cardiac energy status, however, was suggested by reduction in activity of the nonheme iron-dependent enzyme, succinic dehydrogenase.

Age Factors↗
PubMed1978

A quantitative estimation of the depletion of the granules of argyrophile cells in the gastrointestinal tract of reserpine treated Rhesus monkeys.

The depletion of the granules of argyrophile cells following administration of reserpine has been studied at various levels of the gastrointestinal tract of the Rhesus monkey. Granulation of the cells has been estimated by the photometric method of SINGH(1976). The argyrophile cells that persist after reserpine administration show a statistically significant reduction in their granulation as compared to cells of untreated controls (P less than 0.001).

Animals↗