Naunyn-Schmiedeberg's archives of pharmacology
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Naunyn Schmiedebergs Arch. Pharmacol. · Oct 1991
Beta-adrenoceptors in the transplanted human heart: unaltered beta-adrenoceptor density, but increased proportion of beta 2-adrenoceptors with increasing posttransplant time.
To study whether in the (denervated) transplanted human heart beta-adrenoceptors are up-regulated we determined in right ventricular endomyocardial biopsies (weighing 2-7 mg) of 8 heart transplant recipients beta-adrenoceptor density and beta 1:beta 2-adrenoceptor ratio in weekly, later monthly intervals for 6-18 posttransplant months. beta-adrenoceptor density was assessed by 1-2 concentration (-)-[125I]-iodocyanopindolol (ICYP, 200 and 150 pmol/l) binding, the beta 1:beta 2-adrenoceptor ratio by a beta 1-adrenoceptor saturating concentration of the selective beta 1-adrenoceptor antagonist CGP 20712 A (500 nmol/l). In biopsies taken from the donor hearts immediately before transplantation beta-adrenoceptor density was 64.5 +/- 6.3 fmol ICYP bound/mg protein (n = 5), the beta 1:beta 2-adrenoceptor ratio 81.2 +/- 2.2:18.8 +/- 2.2%. beta-Adrenoceptor density did not change during the whole period investigated; it was in the first 9 posttransplant weeks 73.1 +/- 8.3 (n = 22) and after 4-18 months 74.2 +/- 7.6 fmol/mg protein (n = 16). ⋯ There is, however, a gradual decline in beta 1- and increase in beta 2-adrenoceptors with increasing posttransplant time. As noradrenaline acts in the human heart solely at beta 1-adrenoceptors, while adrenaline activates both beta 1- and beta 2-adrenoceptors with about the same potency, with increasing posttransplant time (and increasing proportion of beta 2-adrenoceptors) adrenaline may play an important role for regulation of contractility and/or heart rate in heart transplant recipients.
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Naunyn Schmiedebergs Arch. Pharmacol. · Aug 1990
A bradykinin antagonist inhibits carrageenan edema in rats.
Bradykinin has been implicated in acute inflammatory reactions. Intradermal injection elicits increased vascular permeability and hyperalgesia, and bioassays have suggested increased bradykinin concentration in inflammatory exudates. Poorly specific inhibitors of kallikrein, the enzyme catalyzing formation of bradykinin, inhibit certain acute inflammatory reactions. ⋯ Subplantar injection of carrageenan led to an increase in immunoreactive bradykinin and metabolic product, desArg9bradykinin. NPC 567 inhibited the development of edema in response to carrageenan, to a maximum 65%. Thus, bradykinin appears to be a major mediator of increased vascular permeability in response to carrageenan.
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Naunyn Schmiedebergs Arch. Pharmacol. · Jun 1990
Nimodipine has no beneficial effect on neurological outcome in a cardiopulmonary arrest model in the rat.
Brain damage after resuscitation from cardiac arrest is believed to be related to calcium influx in ischaemic neurons and to postischaemic calcium-dependent vasospasm. We therefore evaluated the potentially protective effects of the calcium-entry blocker nimodipine in a cardiopulmonary arrest model in the rat. Male Wistar rats were anaesthetized with ketamine (group I) or hexobarbital (group II) and subjected to a KCl-induced cardiac arrest during 7 min (group I) or 12 min (group II). ⋯ Nimodipine, in the doses tested, had no beneficial influence on the 7 day survival rate, nor on the occurrence of seizures and the neurological and histopathological scores in the rats surviving after 7 days. With the highest dose of nimodipine, there was even a trend towards a decrease of the survival rate, probably related to the drug's hypotensive effect. Therefore, our data do not show a protective effect of nimodipine after cardiac arrest.
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Naunyn Schmiedebergs Arch. Pharmacol. · Jan 1990
Effects of the benzodiazepine receptor agonist midazolam and antagonist flumazenil on 5-hydroxytryptamine release from guinea-pig intestine in vitro. Indirect support for a "natural" benzodiazepine-like substance in the intestine.
Isolated segments of the guinea-pig small intestine and the guinea-pig stomach were vascularly perfused and the release of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid into the portal venous effluent determined by high pressure liquid chromatography with electrochemical detection. Test substances were applied intraarterially. The benzodiazepine receptor agonist, midazolam, concentration-dependently increased (by 58%, at 1 nmol/l) and decreased (by 32%, at 100 nmol/l) the release of 5-HT from small intestine preparations. ⋯ In the absence of tetrodotoxin, flumazenil (10 nmol/l) decreased also the release of 5-HT and its metabolite from the perfused stomach by about 40%, whereas midazolam (1 nmol/l) caused an increase by about 60%. In conclusion, benzodiazepine receptors modulate the previously described intrinsic GABAergic regulation of 5-HT release from enterochromaffin cells in the guinea-pig intestine. It is suggested that an endogenous benzodiazepine-like substance of non-neuronal origin is present in the small intestine and stomach of the guinea-pig.
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Naunyn Schmiedebergs Arch. Pharmacol. · Dec 1989
Peripheral presynaptic and central effects of clonidine, yohimbine and rauwolscine on the sympathetic nervous system in rabbits.
The function of presynaptic alpha 2-autoreceptors at postganglionic sympathetic neurones under conditions of normal, ongoing sympathetic impulse traffic was studied in anaesthetized rabbits (alfadolone + alfaxalone). Clonidine was used as an alpha 2-adrenoceptor agonist, and yohimbine and rauwolscine were used as antagonists. Mean arterial pressure, postganglionic renal sympathetic firing rate, arterial plasma noradrenaline concentration and heart rate were measured before (basal values) and at the end of 3-min infusions of sodium nitroprusside and phenylephrine, which were given to modulate efferent activity in the sympathetic nervous system through the baroreflex. ⋯ The simultaneous measurement of postganglionic sympathetic nerve activity and the arterial plasma noradrenaline concentration proved suitable to differentiate central (or ganglionic; this distinction was not possible) effects of alpha 2-adrenoceptor ligands from peripheral presynaptic effects. The results show that endogenous presynaptic, alpha 2-adrenergic autoinhibition of noradrenaline release from postganglionic sympathetic neurones operates physiologically in anaesthetized rabbits with ongoing, uninterrupted sympathetic nerve activity. The results also indicate that blockade of alpha 2-autoreceptors enhances the sympathetic reflex compensatory response to a hypotensive stimulus.