Biomedical subjects
Publications and source records attributed to W Ferrari.
Intravenously injected cholecystokinin octapeptide (CCK-8) (5-20/micrograms/kg) and caerulein (1.25-10/micrograms/kg) caused a prompt, dose-dependent and sustained improvement in blood pressure, pulse amplitude and survival in rats subjected to otherwise invariably fatal hemorrhagic shock.
To gain direct insight into the mechanism of sodium deoxycholate (DOC)-induced enhancement of gastroenteral heparin absorption in rats, we performed light and electron microscopic examination of the mucosa of the small intestine of animals treated orally with DOC, heparin or DOC plus heparin. The sole morphological change observed after DOC and DOC plus heparin administration was a marked reduction in the length and distribution of glycocalyx filaments on the microvilli of epithelial cells. The morphological picture had reverted to normal after 24 h, when the promotion of enteral heparin absorption by DOC is greatly reduced. Thus, we suggest that DOC may promote the enteral absorption of heparin in rats by affecting some as yet unidentified barrier mechanism requiring glycocalyx integrity.
Phentolamine (Phe) prevents the induction by epinephrine (E: 1800 nmol/kg, i.v.) of lung edema (LE) in urethane-anesthetized and bivagotomized rats in a dose-related manner (from 246 to 3933 nmol/kg, i.v.). Since Phe blocks and E activates both alpha 1- and alpha 2-adrenoceptors, the evidence does not allow us to link LE to selective (alpha 1 or alpha 2) or non-selective (alpha 1 + alpha 2) alpha-adrenoceptor activation. Accordingly, we tried to find out whether: phenylephrine (PE), a selective alpha 1-adrenoceptor agonist, and B-HT 920, a selective alpha 2-adrenoceptor agonist, would cause LE; prazosin (Praz), a selective alpha 1-adrenoceptor antagonist, and yohimbine (Yoh), a selective alpha 2-adrenoceptor antagonist, would protect rats against LE caused by E or PE. We found that: 1) PE (from 736 to 5892 nmol/kg, i.v.), but not B-HT 920 (from 190 to 12200 nmol/kg, i.v.), caused LE, while both drugs increased arterial blood pressure; 2) Praz prevented induction of LE, whether by E (1800 nmol/kg, i.v.) or by PE (5892 nmol/kg, i.v.), in a dose-related manner (from 15 to 119 nmol/kg, i.v.). In contrast, Yoh was ineffective at doses up to 7675 nmol/kg, i.v. We conclude, therefore, that E-induced LE in urethane-anesthetized and bivagotomized rats strictly depends on alpha 1-adrenoceptor activation. The outcome of E-induced LE is usually rat death, the incidence of which depends on the dose. Since alpha 1-adrenoceptor agonists rank in the same order of potency for the induction of death as for that of LE, and since Phe and Praz protect from death at LE-preventing doses, there seems to be some link between LE and death, even though protection against death is obtained with doses of antagonists lower than those abolishing induction of LE. Finally, alpha 1-agonists cause maximum arterial hypertension at all doses used, irrespective of induction of LE and of protective pretreatment against LE.
In order to elucidate the pathogenesis of epinephrine (E)-induced lung edema (LE) as well as the mechanism of protection afforded by alpha-adrenoceptor blockade in urethane-anesthetized and bivagotomized rats, we investigated the influence of phentolamine (Phe) and prazosin (Praz) on arterial hypertension and LE provoked by continuous intravenous infusion of E and on blood pressure changes in left (LHV) and right (RHV) heart ventricles caused by a bolus injection of E at a LE-producing dose (1800 nmol/kg). Our results show that neither LE nor death are related to E-induced hypertension and also that LE-induction is accompanied by significant increases in LHV (telediastolic and systolic) as well as in RHV (systolic) pressures, of which the LHV telediastolic and the RHV systolic pressure increases are prevented by Phe and Praz at a dose capable of counteracting E-induced LE. The significance of this finding is briefly discussed.
Sodium deoxycholate (DOC), selected as a promoter of gastrointestinal absorption of heparin, was administered orally to rats, followed, at increasing intervals, by heparin. Maximal plasma clearing activity (PC) was obtained with a 60-min interval, though PC was still elicited after 24 h, suggesting that DOC acts on the gastrointestinal mucosa. Inhibition of blood coagulation was also observed after oral heparin. The suggestion that DOC increases heparin absorption is supported by increased plasma levels of heparin. No signs of several gastrointestinal damage were seen.
The mechanism of the contractile effect of dopamine (DA) on the rat isolated seminal vesicle was studied. Cocaine (10 microM/1 in the organ bath, 30 min before DA) and 6-OHDA (50 mg/kg i.v. 24 hr before removal of the seminal vesicle) almost completely prevented the contractile effect of DA. Drugs known to have an affinity for DA receptors or for alpha-adrenoceptors antagonized the contractile effect of DA, the rank order of potency being: prazosin greater than phentolamine greater than yohimbine greater than clonidine greater than sulpiride greater than apomorphine greater than haloperidol. The antagonism was in each case greater against DA than against noradrenaline (NA), used for comparison; selectivity for DA being highest in the case of prazosin and sulpiride. Taken together, these findings indicate that DA makes the rat seminal vesicle contract mostly by means of an indirect mechanism, binding presynaptic DA-receptors and, in part, presynaptic alpha-adrenoceptors as well; or, alternatively, binding presynaptic DA-receptors which have some links with alpha 2-adrenoceptors; the consequence being in either case the release of NA from sympathetic nerve endings.
Aqueous heparin sodium solution dispersed in olive oil administered esophageally to fed rats induced blood plasma clearing activity, inhibition of blood coagulation and increased plasma heparin level. Plasma clearing activity was dependent on heparin dose (125 to 1000 mg/Kg). No plasma clearing activity being observed in pylorus- or coledoch-ligated rats, while heparin absorption reappeared after ox or rat bile administration, we conclude that olive oil favours enteral absorption of heparin by increasing bile function.
Selected non-ionic surfactants of the polyoxyethylene ether series as well as selected bile acids elicit plasma clearing activity (PC) after oral heparin administration by action on the gastro-intestinal mucosa. Evidence obtained indicates that certain structural characteristics are needed for promoting heparin absorption, since this effect is observed with some but not all non-ionic detergents (cetyl and stearyl ethers but not lauryl) and bile components (deoxycholic, chenodeoxycholic and cholic acids, but not ursodeoxycholic or dehydrocholic acids or lecithin). It is suggested that a specific mechanism of action is involved.
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The injection of ACTH 1--24 into the cerebral ventricles in rats markedly reduces the reaction time in the hot-plate test and the nociception threshold in the tail-stimulation test. Morphine antagonizes and naloxone potentiates this hyperalgesic effect of ACTH. It is proposed that ACTH peptides play a physiological role in nociception.
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A series of 3,4-dihydro derivatives of 6-chloro-, 7-chloro-, 5,7-dichloro-, 6,7-dichloro-, 5,7-dibromo-, 5-nitro-7-chloro-, 7-nitro-, 7-amino-1,2,4-benzothiadiazine-1,1-dioxide, various substituted on the heterocyclic carbon, was prepared and tested for cardiovascular activity. It was found that in this series of compounds cardiac activity predominates and is exclusively of the depressant type. Bradycardial activity seems to be affected both by the nature of the substituent on the heterocyclic carbon atom and by the substituents on the benzene ring. An alkyl chain of three carbon atoms, normal or alpha-ethylsubstituted, on C3 and the presence of a chlorine atom in positions 6 or 7 seem to be the most significant structural features for this activity. Some of the substances tested showed a pressor effect (hypotension and/or increase in differential pressure).
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