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Biomedical subjects

M Massi

Publications and source records attributed to M Massi.

At least 109 records · Page 6Linked to original sources

Hypotensive effect in dogs and rats of intravenous injections of the alpha 1-adrenoreceptor antagonist benoxathian.

The hypotensive effect of the alpha 1-adrenoreceptor antagonist benoxathian has been evaluated in rats and dogs, in comparison to that evoked by WB 4101 and prazosin. In anaesthetized dogs, i.v. injection of benoxathian (25-100 micrograms/kg), WB 4101 (5-25 micrograms/kg) and prazosin (50 micrograms/kg) produced an immediate fall in diastolic blood pressure, which reached a maximum at about 30 sec after drug administration. Whereas the hypotensive effect of prazosin persisted up to 3 hr following injection, the effect of both benoxathian and WB 4101 completely disappeared after 30-60 min. The hypotensive effect of benoxathian was dose-dependent. Pressor responses to i.v. noradrenaline (5 micrograms/kg), adrenaline (5 micrograms/kg) and phenylephrine (20 micrograms/kg) were markedly inhibited (60-75%) by benoxathian (100 micrograms/kg) whilst the pressor response to angiotensin II (0.05 micrograms/kg) was not reduced, but indeed slightly increased. The hypotensive effect of benoxathian (100 micrograms/kg) was abolished following pre-treatment with prazosin (50 micrograms/kg) or hexamethonium (1000 micrograms/kg). In anaesthetized rats similar results were obtained although recovery in blood pressure from the initial drop after i.v. injection of the drugs was slower than in dogs. Benoxathian was slightly more toxic than WB 4101 in rats. In conclusion, present findings show that benoxathian causes a profound hypotensive effect in dogs and in rats through postsynaptic alpha-adrenoreceptor blockade; however its effect, as well as that of WB 4101, is shorter lasting than that of prazosin.

Adrenergic alpha-Antagonists↗

Suppression of drinking but not feeding by central eledoisin and physalaemin in the rat.

The tachykinins, eledoisin and physalaemin, given by intracerebroventricular (i.c.v.) injection have been shown to be potent antidipsogenic agents in rats. To evaluate their selectivity of action on rat ingestive behaviors, we compared their effects following i.c.v. injection on the intake of water, of milk containing 3.5 or 15% fat, and of solid food. The two tachykinins inhibited water intake induced by i.c.v. angiotensin II or by cellular dehydration, but did not reduce the intake of 15% fat milk or of solid food. The intake of 3.5% fat milk was inhibited only by the highest dose (1000 ng/rat) of eledoisin which also increased grooming and locomotion. The present findings suggest that in adult rats central eledoisin and physalaemin exert a selective suppressive effect on drinking behavior without affecting feeding.

Animals↗

Synthesis and dopaminergic activity of trans-6-methyl-7a,8,9,10,11,11a-hexahydro-7H-pyrrolo[3,2,1-gh]- 4,7-phenanthroline and trans-1,2,3,4,4a,5,6,10b-octahydro-4,7-phenanthroline derivatives.

The synthesis and dopamine agonist activity of some derivatives of trans-6-methyl-7a,8,9,10,11,11a-hexahydro-7H-pyrrolo[3,2,1-gh]- 4,7-phenanthroline (6a-c) are reported. These compounds can be regarded as analogues of ergoline derivatives with the indole nucleus replaced by indolizine. These congeners have been evaluated as inhibitors of prolactin release in vivo. trans-6-Methyl-8-ethyl-7a,8,9,10,11,11a-hexahydro-7H-pyrrolo[3,2,1-gh]- 4,7-phenanthroline (6b) proved to produce a dose-dependent inhibition of serum prolactin that was almost complete at the highest dose employed. Although effective, this compound was far less potent than bromocriptine. The 8-propyl derivative 6c was weakly active only at very high doses, and the 8-methyl derivative 6a proved to be completely ineffective. trans-4-Propyl-1,2,3,4,4a,5,6,10b-octahydro-4,7-phenanthroline (7), a molecular simplification of hexahydropyrrolo-4,7-phenanthroline, proved to be the most potent among the newly synthesized compounds. These results, taken together with those of previous studies, suggest that the presence of the nitrogen of the indolizine nucleus and the N-7 in the octahydro-4,7-phenanthroline 7 are significant for the interaction with the dopamine receptor involved in the control of prolactin release.

Animals↗

Water intake modifications induced by tachykinins, bombesins and opioid peptides.

Nonmammalian peptides of the tachykinin, bombesin and opioid families, injected into the brain ventricles, potently and specifically affect drinking behaviour of rats and pigeons. These peptides, or at least their counterparts, have been found in the brain of mammals and birds. It has been hypothesized that these endogenous brain peptides belong to a "brain peptidergic system" which participates in the control of water intake and body fluid homeostasis.

Angiotensin II↗

Possible influence of tachykinins on body fluid homeostasis in the rat.

The effect on water intake, urine flow and vasopressin release of intracranial injections of substance P, physalaemin and eledoisin was studied in Wistar and Brattleboro, homozygous and heterozygous, rats. The tachykinins strongly inhibited water intake both in Wistar and in Brattleboro, homozygous and heterozygous, rats. Physalaemin and eledoisin reduced urine flow in Wistar and heterozygous, but not in homozygous, Brattleboro rats. Substance P never affected urine elimination. Physalaemin and eledoisin produced a dose-dependent, long lasting release of vasopressin in Wistar rats. Substance P did not affect the release of vasopressin. The results suggest that both substance P and physalaemin could influence brain mechanisms which control water intake, acting as thirst inhibitors, and that physalaemin could also participate in body fluid control by conserving water through vasopressin release.

Animals↗

Muscimol inhibits ADH release induced by hypertonic sodium chloride in rats.

The effect of the GABA-agonist muscimol on ADH release induced in rats by administration of hypertonic sodium chloride solutions was studied by means of intracerebroventricular and intraperitoneal injections of the drug. Injected by the intracerebroventricular route, muscimol produced a significant reduction of plasma ADH concentration not only in animals treated with hypertonic sodium chloride, but also in unstimulated animals. Following intraperitoneal administration larger doses were required to produce such an effect, thus suggesting a central site of action for the effect of muscimol on ADH release. Bicuculline, given intraperitoneally before muscimol injection, completely blocked ADH inhibition induced by muscimol, thus suggesting a specific involvement of GABAergic receptors. These findings indicate that GABAergic mechanisms may be involved in the regulation of body fluids in the rat by affecting ADH release.

Animals↗

Drinking stimulation by a new angiotensin, crinia-angiotensin II, in rats and pigeons.

The effects of crinia-angiotensin II on water intake and arterial blood pressure were investigated in conscious rats and pigeons. Injected by intravenous route to rats and pigeons, crinia-angiotensin II produced a hypertensive response practically identical to that induced by intravenous angiotensin II. Injected by intracerebroventricular route crinia-angiotensin II proved to be as active as angiotensin II in eliciting water intake in pigeons, while being less effective in rats. These findings, while demonstrating that naturally occurring angiotensins may be as active as angiotensin II itself in eliciting drinking, suggest that different molecular requirements must be satisfied to activate the angiotensin receptors for drinking in rats and pigeons.

Angiotensin II↗

The effects of changes in osmolality and sodium concentration on angiotensin-induced drinking and excretion in the pigeon.

1. The pigeon drank copiously after a short latency in response to intracerebro-ventricular (I.C.V.) infusion of angiotensin II dissolved in isotonic NaCl. There were small, insignificant increases in urinary excertion so that the increased water intake caused the pigeon to go into positive fluid balance. Water was chosen in preference to 0.3 M-NaCl, which was also available to drink in these experiments.2. I.C.V. infusion of angiotensin dissolved in water, or in isotonic or hypertonic solutions of non-eletrolytes, or in KCl or CaCl(2) resulted in about half the water intake produced by angiotensin dissolved in isotonic NaCl.3. I.C.V. infusion of hypertonic NaCl alone caused drinking. I.C.V. infusion of angiotensin dissolved in hypertonic NaCl caused an amount of water to be drunk that was a simple addition of the amounts drunk in response to angiotensin dissolved in isotonic NaCl and to the extra amount of NaCl.4. Drinking in response to I.C.V. infusion of two other dipsogenic peptides, eledoisin and physalaemin, was similarly affected by the composition of the solutions in which they were dissolved.5. The pigeon also drank in response to intravenous (I.V.) infusion of angiotensin II dissolved in isotonic NaCl. Urine flow and sodium excretion increased markedly so that the pigeons just maintained fluid balance.6. In contrast to the reduction in intake when angiotensin was infused I.C.V. dissolved in hypertonic non-electrolytes, I.V. infusions of angiotensin dissolved in hypertonic non-electrolytes caused enhanced drinking, compared with the corresponding infusions of angiotensin dissolved in isotonic NaCl.7. Drinking induced by I.V. infusion of angiotensin was little affected by simultaneous I.C.V. infusion of isotonic or hypertonic sucrose, or water, but it was increased by simultaneous I.C.V. infusion of hypertonic NaCl.8. Drinking responses were partly additive when angiotensin was given by simultaneous I.C.V. and I.V. infusion.9. The increased urine flow and electrolyte excretion in response to I.V. infusion of angiotensin were little affected by simultaneous I.C.V. infusion of angiotensin.10. These experiments suggest that in the pigeon there may be separate sets of receptors in the cerebral ventricles for initiating drinking, one set responding to angiotensin, another to hypertonic NaCl. Outside the blood-brain barrier, and accessible to blood-borne substances, there may also be separate sets of receptors, one set responding to angiotensin, another to increases in effective osmolality of the blood.

Angiotensin II↗

Dual effect of naloxone on drinking behaviour of rats.

Naloxone, administered to rats subcutaneously or by i.c.v. route, produces a dose-dependent inhibition of water intake elicited by angiotensin II or water deprivation. However, doses of the drug which do not affect drinking inhibit the antidipsic effect of subcutaneous morphine. The larger is the dose of morphine, the larger is the antimorphinic effect evoked by naloxone. These data would suggest that, at least in respect to the effects of narcotics on water intake, naloxone is a partial agonist of the nalorphine type, but the slopes of naloxone and of morphine dose-response regression lines are not in keeping with this hypothesis. Thus, the mechanism of the anti-morphic effect elicited by naloxone on drinking behaviour remains to be clarified.

Angiotensin II↗

Modifications of drinking behaviour and of arterial blood pressure induced by tachykinins in rats and pigeons.

Intracerebroventricular injections of the naturally occurring tachykinins eledoisin, physalaemin and substance P elicit a powerful antidipsogenic effect in the rat, while in the pigeon they potently stimulate water intake. The aim of this paper was to study in conscious rats and pigeons the vascular effect of these peptides and to compare this effect to the one elicited on water intake. The results of these experiments demonstrate that there is no direct relationship between the two effects. Our findings suggest that the effect of these peptides on water intake might be specific on CNS and not related to their vascular activity.

Animals↗

Dipsogenic effect of angiotensin II, bombesin and tachykinins in the duck.

The effect on drinking behaviour of intracerebroventricular injections of angiotensin II, bombesin, eledoisin and substance P was studied in the duck. While substance P was almost completely ineffective, angiotensin II, bombesin and eledoisin elicited a clear dipsogenic response which was dose-dependent and apparently specific. Angiotensin II was about 10 times more potent than bombesin and far more potent than eledoisin. These results confirm once more the wide phylogenetic distribution of the dipsogenic response to angiotensin II. Furthermore, they show that bombesin and eledoisin, which potently inhibit water intake in the rat, exert in the duck a dipsogenic effect strictly parallel to that elicited in the pigeon. On the basis of the animal species so far tested it is possible to hypothesize that bombesin and tachykinins stimulate water intake in birds, while inhibiting drinking in mammals.

Angiotensin II↗

Effect of subcutaneous injections of carbuterol on renin release and water intake in the rat.

The effect on renin release and water intake of subcutaneous injections of the beta-adrenergic agonist carbuterol has been studied in the rat. Carbuterol, as well as isoprenaline, elicited a clear dipsogenic effect, dose-dependent, apparently mediated by stimulation of the renin-angiotensin system. The dipsogenic potency of carbuterol, in comparison to that of isoprenaline, was weaker; the ratio of dipsogenic potency between the two substances proved to be very similar to that of their relative vasodepressor activities. These findings appear to be consistent with the hypothesis that beta 2-adrenergic receptors of vascular type are involved in renin release and water intake stimulation.

Animals↗