The hypotensive action of bradykinin in the guinea pig and cat]

In the guinea-pig as in the cat, the duration of the bradykinin general arterial hypotension is reduced by indometacine. This decrease is due to the inhibition of the synthesis of endogenous vasodilatator prostaglandins. The guinea-pig and the cat present the same type of reactivity for bradykinin as the rabbit, the dog and the rat.     

Hemodynamic aspects of the hypotensive action of captopril

Captopril was tested in acute experiments on anesthetized cats subject to cardiopulmonary bypass. The drug was shown to reduce total peripheral vascular resistance and to increase vascular bed capacity.     

Kallikrein-thrombolytic and hypotensive action in cats--preliminary results.

An intravenous injection of kallikrein produced hypotensive and thrombolytic effects in anesthetized cats, using the blood superfused tendon technique. The thrombolytic action of kallikrein was mediated by an unstable substance. The generation of this substance was abolished by either acetylsalicylic acid (ASA) or aprotonin and enhanced by captopril. The hypotensive action of kallikrein was only partially inhibited by ASA. It is proposed that both these pharmacological effects of kallikrein are mediated by bradykinin which in turn releases prostacyclin from the endothelium. However, in contrast to the thrombolytic effect of kallikrein which is totally mediated by prostacyclin the hypotensive action of kallikrein depends not only on prostacyclin but also on another endothelium-derived vasorelaxant, e.g. EDRF.     

Chronic caffeine consumption potentiates the hypotensive action of circulating adenosine

Mean arterial blood pressure was correlated with arterial plasma adenosine levels during intravenous adenosine infusion in unanesthetized, unrestrained rats. Elevation of plasma adenosine to 5 to 6 microM (normal range 1.6 to 4.6 microM) depressed mean arterial pressure by 20 to 30 percent: this was blocked by a single caffeine injection (15 mg/kg). In contrast, caffeine consumption for 3 weeks, followed by a 1-day washout, markedly potentiated responses to adenosine, plasma levels in the 2 to 4 microM range causing 30 to 40 percent reductions in mean arterial pressure. These observations suggest that chronic occupancy of cardiovascular adenosine receptors by caffeine can enhance tissue responsiveness to adenosine, and that endogenous adenosine might act as a circulating hormone.     

Role of ventral surface of brain stem in control of arterial pressure and in hypotensive action of clonidine]

Superficial destructions of the brain stem have been performed in cats at the level of the chemosensitive areas "S". These destructions produced a drop in blood pressure, which was transient in 9 and definitive in 4 animals. In 6 sham-operated animals, clonidine (15 mug/kg), injected intravenously, always induced a marked fall in blood pressure, whereas in the 10 animals which have maintained or regained normal blood pressure after the destruction of the areas S, clonidine no longer induced any decrease in blood pressure. These results suggest that the integrity of the areas S is necessary for the development of the hypotensive action of clonidine. This hypotensive drug may act, at least at that level of the ventral surface of the brain stem, through an inhibition of a vasopressive structure.     

Naloxone reverses the serotonin dependent hypotensive action of CGP 6085 A

CGP 6085 A, a specific 5-hydroxytryptamine (5-HT), serotonin uptake inhibitor, is also a potent hypotensive agent. Its depressor effect in the spontaneously hypertensive (SH) rats correlates well with its ability to inhibit serotonin uptake. Here we report that the effects of CGP 6085 A on arterial blood pressure were greatly reduced in rats pretreated with p-chlorophenylalanine (pCl-Phe), a specific depletor of serotonin. Moreover, in rats pretreated with the serotonin antagonist, methysergide, CGP 6085 A did not produce significant hypotension. We also found that centrally administered naloxone reverses the hypotensive effect of CGP 6085 A. These results provide further evidence for the existence of an important serotonin-opioid interaction in the mechanisms of arterial blood regulation in the rat.     

Differences in the mechanism of the antihypoxic action of benzodiazepine receptor agonists and muscimol

Neuropharmacological analysis of previously revealed antihypoxic activity of benzodiazepines (BDZ) has been performed in experiments on mice exposed to hypoxia. Antihypoxic effect of diazepam is shown to be antagonized by the central BDZ receptor blocker, Ro 15-1788. A certain degree of antihypoxic activity also abolished by Ro 15-1788 is exhibited by hypothetical ligands of BDZ receptors: inosin, nicotinamide, ethyl-beta-carboline-3-carboxylate. The effect of dipyridamole, a drug with high affinity for BDZ receptors of the peripheral type is not antagonized by Ro 15-1788, another evidence of Ro 15-1788 affinity precisely to the central BDZ receptors. GABA-mimetics (muscimol and GABA cetyl ester) were also found to have marked antihypoxic activity. Unlike BDZ receptor agonists, this effect is reduced by bicuculline and not by Ro 15-1788. The data obtained suggest that antihypoxic activity of BDZ is caused by their direct interaction with the central BDZ receptors, probably with the type which is not modulated by GABAA receptors.     

Effector modeling of the action of ligands of the GABA receptor complex: functional interactions of muscimol and exogenous modulators of the complex]

In comparison with the literature data the pharmacological effects of muscimol (MS) on mice organism were studied under the condition of administration of the exogenic ligands of GABA-receptor complex GABA antagonist bicuculline (BC), chloride ionophor blocking agent pentylenetetrazole (PZ), phenazepam (BD), sodium barbital (BB) and GABA synthesis antagonist--thiosemicarbazide (TS). Antagonism of MS to the anticonvulsant effect of BB and BD at the administration of BC to the animal was observed, while no effect was observed at the administration of PZ. However at the administration of TS to the experimental animals MS exhibits anticonvulsant effect. The observed properties (partial agonism/partial reverse agonism) of MS at its effect to the whole system are probably determined by the level of endogenic GABA and its changes due to the administration of TS and functional state of GABA--receptor system modified with the exogenic ligand BC.     

3H]muscimol binding sites increased in autopsied brains of chronic schizophrenics

[3H]muscimol binding and glutamic acid decarboxylase (GAD) activity in the prefrontal cortex and caudate nucleus of autopsied brains from 19 chronic schizophrenics and 17 control subjects were investigated. In the schizophrenics, saturation analysis with varying concentrations of [3H]muscimol revealed an increase in the number of GABAA receptors, but there was no significant difference in the affinity. In addition, the enhancement of [3H]muscimol binding by diazepam was significantly greater in schizophrenics than in controls. GAD activity did not differ between controls and schizophrenics. The possibility that GABAergic mechanisms might play a role in case of chronic schizophrenia should be given further attention.     

The influence of propranolol on the hypotensive action of ketanserin in normotensive rats

In normotensive rats the effect of different doses of propranolol (1.0, 5.0 and 10.0 mg/kg i.p.) and ketanserin (10.0 mg/kg p.o.) on mean blood pressure and heart rate and on cardiovascular response to noradrenaline (0.1, 0.3, 0.5, 0.7 and 1.0 micrograms/kg i.v.) was examined. The drugs were given separately or together. Propranolol slightly reduced the hypotensive effect of ketanserin. On the other hand a decrease in heart rate caused by propranolol was not affected by ketanserin. Our results show that propranolol given with ketanserin did not change the effect of the latter on the cardiovascular system.