PubMed Health⌕ Search

Biomedical subjects

G Dondi

Publications and source records attributed to G Dondi.

At least 19 recordsLinked to original sources
PubMed1996

Evaluation of the reperfusion syndrome after liver ischemia in the rat.

Hepatic surgery in man often requires a transient interruption of the blood flow to the liver. After the vascular declamping the hepatic reperfusion induces a group of phenomena commonly called "reperfusion injuries." The aim of this study was to evaluate the presence and effect of vasoactive agents that could induce the acute pulmonary arterial hypertension which contributes to reperfusion injury. Wistar rats were used. The hepatic ischemia was induced by crossclamping the whole hepatic hilus for 20, 40, and 60 min. In control experiments a sham operation was performed. Blood samples were collected from the suprahepatic inferior vena cava. Strips of the main pulmonary artery were set up in an isolated organ bath and tested for the response to noradrenaline, adrenaline, KCl, and plasma samples. Plasma levels of catecholamines were determined by high-performance liquid chromatography. Plasma concentration of noradrenaline significantly increased from 1.6 +/- 0.4 (control) to 10.8 +/- 2.9 ng.ml-1 and adrenaline concentration rose from 2.7 +/- 0.7 to 38.7 +/- 7.6 ng.ml-1 after ischemia. Noradrenaline potency, compared to control values, significantly increased after prolonged liver ischemia. The plasma samples collected after prolonged liver ischemia caused a greater contraction of the pulmonary artery than from control plasma. This contraction is partially inhibited by phentolamine. We conclude that hepatic ischemia modifies the response of the pulmonary artery to exogenous noradrenaline. At the same time it induces an increase in the plasma levels of adrenaline and noradrenaline. The resulting combined effect may cause the pulmonary hypertension which has been observed in reperfusion injury.

Animals↗
PubMed1993

Synthesis and muscarinic activity of the chiral forms of methylenemuscarones.

The synthesis of the two pairs of enantiomers of methylenemuscarones 3 and 4 has been accomplished by using (R)- and (S)-lactic esters as starting materials. Due to the existence of different muscarinic receptor subtypes, the compounds were examined for their ability to bind membranes from cerebral cortex (M1), heart (M2), and salivary glands (M3) and were assayed in "in vitro" functional tests as well. The results of such an investigation put in evidence that, in both binding and functional tests, (-)-3 (2S,5S) and (-)-4 (2R,5S) were the eutomers and shared the stereochemistry of the eutomer of muscarone and allomuscarone respectively. It is worth noting that the distomer of 3 and 4 behaves as a partial agonist in the cardiac tissue and as a full agonist in the other preparations. This peculiarity of the chiral forms of 3 and 4 could account for the remarkable selectivity for the ileum observed in the corresponding racemates.

Animals↗
PubMed1992

Synthesis and pharmacological investigation of stereoisomeric muscarines.

The synthesis of the eight stereoisomers of muscarine has been efficiently accomplished by utilizing the two enantiomers of lactic esters as starting material. The synthetic strategy is based on a SnCl4-catalyzed addition of allyltrimethylsilane to O-protected lactic aldehydes followed by an iodocyclization process. All the final derivatives possess an enantiomeric excess higher than 98%. The four pairs of enantiomers bound to M1, M2, and M3 muscarinic receptor subtypes in membranes from cerebral cortex, heart, and salivary glands, respectively, and recognized heterogeneous states of the receptors. Of the eight isomers, only natural muscarine (+)-1 recognized three affinity states of the M2 receptor. The compound was also the only one to show selectivity in the binding study, demonstrating 37- to 44-fold higher affinity for the M2 than for the M1 or M3 receptors. In addition, the compounds were tested in functional assays on isolated guinea pig atria (M2 receptors) and ileum (mixed population of M2 and M3 receptors) and their muscarinic potencies were determined. Among the eight isomers, again only (+)-1 enantiomer was found to be very active on both tissues. Its potency was more than two orders of magnitude higher than that of its enantiomer (-)-1 as well as the other six isomers. The eudismic ratios (E.R.) deduced from the two functional tests were 324 and 331.

Animals↗
PubMed1984

Inhibition of norepinephrine- and 5-hydroxytryptamine-induced contraction on rat aorta by dihydroergocristine.

Norepinephrine (NE), 5-hydroxytryptamine (5-HT) and tyramine (Tyr) elicited concentration-related contractile responses on rat aorta strips. The maximum contractile responses evoked by 5-HT and NE were comparable; on the contrary the maximum response induced by Tyr was only 50% that of NE. Pretreatment with reserpine failed to modify the concentration-response curve for both Tyr and 5-HT. 5-HT concentration-response curves antagonized competitively by methysergide, 5-HT may be assumed to act directly on 5-HT receptors. The concentration-response curve for NE was shifted to the right by dihydroergocristine (DHEC) and, at least in a certain dose range, the observed agonist-antagonist interaction fulfilled the condition for competitive antagonism. With higher doses a decrease of the maximum response was obtained. DHEC antagonized 5-HT in a non competitive manner, shifting to the right and flattening the dose-response curves of this agonist. The doses needed to obtain such anti-5-HT effect are not too far from those giving alpha-adrenolytic effects.

Animals↗
PubMed1983

Action of papaverine and verapamil on norepinephrine and calcium evoked contraction of vascular and non vascular smooth muscle.

On isolated rat vas deferens both papaverine and verapamil show a non competitive antagonism against norepinephrine and a competitive antagonism against Ca2+. Verapamil is nearly 100 times more active than papaverine. On the main pulmonary artery and on the thoracic aorta of the rabbit, verapamil shows a competitive antagonism against both norepinephrine and Ca2+ but it is more effective (almost 100 times) against Ca2+ than norepinephrine. Papaverine also shows a competitive antagonism against norepinephrine but a non competitive antagonism against Ca2+. The contrasting results obtained on rat vas deferens and rabbit vessels might be due to: 1) mechanism(s) of action of the agonist; 2) properties of the biological object as far concerns receptor activation and mechanism(s) of excitation-contraction coupling; 3) mechanism(s) of action of spasmolytic drugs. All these factors act in a cooperative way in determining the quality and the quantity of the observed responses.

Animals↗
PubMed1983

Action of cocaine on norepinephrine- and calcium-induced contraction of vascular smooth muscle.

The action of cocaine on the norepinephrine- and calcium-induced contraction of the thoracic aorta and the main pulmonary artery of the rabbit was studied. Cocaine, depending on the employed concentrations, shows a competitive or a non-competitive antagonism against norepinephrine, while, against calcium, cocaine, at the used concentrations, shows a competitive antagonism. The results are discussed in the light of literature data obtained from different preparations of several animal species. It is clear that the actions of local anesthetics must be evaluated through a wide range of doses and by considering the properties of the biological object.

Animals↗
PubMed1980

Action of local anesthetics on basal tone of rat vas deferens and on response to norepinephrine and calcium.

The actions of three local anesthetics (cocaine, procaine and tetracaine) on basal tone of isolated vas deferens from control and reserpinized rats were studied. The influence of these anesthetics on responses to norepinephrine and calcium was also examined. Cocaine, procaine and tetracaine, in the order, induced phasic and tonic contractions, the latter ones probably due to catecholamine release. The local anesthetics, at the lowest doses, produced an elevation of the maximum response to norepinephrine, as well as a leftward shift of the dose-response curve. The highest doses of local anesthetics inhibited the response to norepinephrine in a non-competitive way, while the response to calcium was competitively inhibited. In this connection, tetracaine proved to be the most active compound. The distinction between destabilizing and stabilizing effects on membrane is pointed out and discussed.

Anesthetics, Local↗
PubMedDate not supplied

The inhibitory effect of differently classified calcium antagonists on the calcium- and epinephrine-induced responses of isolated guinea-pig atria.

The effects of calcium antagonists diltiazem, flunarizine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7) were investigated on the calcium- and epinephrine-induced responses of guinea-pig spontaneously beating atria. All these calcium antagonists showed negative chronotropic and inotropic effects. Diltiazem (3 x 10(-8) M to 1.8 x 10(-7) M) antagonized both the action of epinephrine and calcium in a different manner but at the same concentrations. Flunarizine (1 x 10(-6) M to 1 x 10(-5) M) also antagonized both the action of epinephrine and calcium; but flunarizine weakly inhibits the calcium response at concentrations which have considerable antiadrenergic action. Only at the highest concentrations did both calcium antagonists show a decrease of the epinephrine maximum effect. W7 (1 x 10(-5) M to 1 x 10(-4) M) showed a mainly non-competitive antagonism against epinephrine but was practically ineffective against calcium. The results obtained suggest that a pharmacological prerequisite exists for classifying a calcium antagonist as a calcium entry blocker in the atrial muscle. Such a drug does not produce selective inhibition to calcium- and epinephrine-induced responses. The ability or inability to inhibit the response to calcium represents the discriminant parameter for the action site of the calcium antagonist which are transmembranal fluxes or intracellular mechanisms respectively.

Animals↗