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Biomedical subjects

E Ragazzi

Publications and source records attributed to E Ragazzi.

At least 55 records · Page 3Linked to original sources
PubMed1994

Dual effect of ATP and UTP on rat atria: which types of receptors are involved?

The effects of adenine compounds and UTP were examined in electrically driven rat left atria. ATP, ADP, AMP, adenosine and UTP caused a dual inotropic effect: first a rapid decrease in contractility, and second an increase in contractile tension. alpha,beta-Methylene ATP caused an increase in contractile tension only, whereas 2-methylthio-ATP only induced a negative inotropic effect, 1,3-Dipropyl-8-cyclopentylxanthine inhibited the negative effects of ATP and adenosine, whereas 3,7-dimethyl-1-propargylxanthine did not influence the effects of ATP. Suramin but not reactive blue 2 antagonized the positive inotropism induced by ATP and alpha,beta-methylene ATP. Suramin also abolished the positive inotropic effect induced by UTP. These results demonstrate that ATP may induce negative inotropism directly by an action on A1-adenosine receptors and positive inotropism by an action on P2x-purinoceptors. UTP induces a positive inotropic effect mediated by suramin-sensitive receptors.

Adenosine Deaminase↗
PubMed1994

Phentolamine and hypoxia: modulation of contractility and alpha 1-adrenoceptors in isolated rat atria.

The hypoxia-induced effects on the binding sites and affinity constant of adrenoceptors, in the presence and absence of phentolamine, were determined for atrial membranes of hearts from normal and genetically hyperlipidaemic Yoshida (YOS) rats. Atrial function was also measured during normoxia and hypoxia, in the presence and absence of phentolamine. Hypoxia increased alpha 1-adrenoceptor density in atrial membranes of normal rats (Bmax 10.6 to 26.7 fmoles/mg protein). Phentolamine prevented the increase in the Bmax of alpha 1-adrenoceptors and increased the equilibrium dissociation constant of these receptors (KD 0.17 to 0.53 nmol/l). Beta-adrenoceptors did not change during hypoxia, but the Bmax was slightly increased (26%) in the presence of phentolamine. Thus, the alpha 1/beta ratio increased from 0.40 in normoxia to 1.06 in hypoxia. In normoxic atria from YOS rats, the alpha 1/beta ratio was already elevated (0.86) in comparison to control rats (mainly due to a higher density of alpha 1-adrenoceptors in atrial membranes from YOS rats). This ratio was not modified by hypoxia (0.84), but decreased when phentolamine was present (0.30). Hypoxia reduced the force of contraction and increased diastolic tension of atria of normal rats, while the sinus rate was not significantly modified. Phentolamine abolished the increase in diastolic tension and reduced the negative effect of hypoxia on contractile force. In YOS rat atria, functional parameters were modified by hypoxia in a qualitatively similar way to that of normal rat atria.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effect of cholesterol-supplemented diet in heritable hyperlipidemic Yoshida rats: functional and morphological characterization of thoracic aorta.

In this study we have considered the possibility of inducing vascular damage in Yoshida Pittsburg (YOS) rat, an inbred strain which has endogenous hyperlipidemia without vascular atherosclerotic damage. Cholesterol-enriched diet (4% cholesterol plus 1% cholic acid and 0.5% thiouracil) was administered to YOS rats, in order to induce atherogenesis. The results indicate that, despite significant increase in serum (about 2-fold) and aortic tissue cholesterol (about 6-fold), no morphological damage occurred. A reduction in acetylcholine-mediated relaxation (of about 37%) was observed. No inhibition of ATP- or sodium nitrite-induced relaxation, or of contraction induced by norepinephrine was seen. Serum triglyceride concentration did not vary after administration of a cholesterol-enriched diet. Our results suggest that in heritable hyperlipidemic Yoshida rat, after 2 months of cholesterol-enriched diet, despite increased serum cholesterol levels, no atheromatous plaque developed on the aortic wall. Impaired vascular function and reductions in the response to acetylcholine were related to changed endothelial cell function. Administration of a high cholesterol diet to YOS rat may represent a new model of mixed endogenous and exogenous hyperlipidemia that can resemble many human dislipidemic diseases and therefore may become a useful tool for the study of isolated endothelial dysfunction.

Acetylcholine↗
PubMed1994

Effect of calcium antagonists on isolated aorta from hypercholesterolemic Yoshida rats of different ages.

1. The in vitro thoracic aorta, precontracted with norepinephrine, KCl or PGF2 alpha of hypercholesterolemic Pittsburg-Yoshida (YOS) and normolipidemic Brown-Norway (BN) rats of two age groups (2 and 18 months), was relaxed by the calcium antagonists verapamil and nifedipine without any difference between age-matched YOS and BN rats. 2. The relaxant activity of verapamil was impaired in aged rats of both strains and with the different contractile agents. Conversely, no variation with aging of the nifedipine relaxing effect was observed on KCl-induced contraction was the nifedipine relaxant effect differently affected by age, both in YOS and BN rats. 3. In conclusion, prolonged exposure to hypercholesterolemia in YOS rat does not affect aortic response to nifedipine and verapamil. Only the aging process was able to affect vascular relaxation to calcium antagonists.

Aging↗
PubMed1994

Protection of atrial function in hypoxia by high potassium concentration.

1. The effects of high extracellular potassium on hypoxia-induced atrial activity and metabolic charge were studied in isolated rat atria. 2. After hypoxia (30 min), contractile tension strongly decreased and diastolic tension increased, while frequency did not change. Adenine nucleotides and creatine phosphate levels did not change, although a significant increase in lactic acid content was observed. 3. High [K+] mostly countered the hypoxia-induced increase in diastolic tension. Moreover, in the presence of high [K+], the hypoxia-induced increase in lactic acid was not significantly different from normoxic controls. 4. Glibenclamide (0.1 microM), a selective K+ATP channel blocker, did not improve the hypoxia-induced depression of atrial function. 5. The physiopathological role of extracellular potassium during cardiac hypoxia is discussed.

Adenine Nucleotides↗
PubMed1994

Purine- and nucleotide-mediated relaxation of rabbit thoracic aorta: common and different sites of action.

The mechanisms of the relaxant effect of purines and pyrimidines in New Zealand rabbit isolated aorta were investigated at endothelial and smooth muscle cell levels. Endothelium-mediated relaxation by ATP was only partially inhibited by the P2-purinoceptor antagonist suramin (0.1 mM). The pyrimidine UTP produced vasodilation by acting at the endothelial level and relaxation was not antagonized by suramin (0.1 mM). This effect was not mediated by P2 purinoceptors, indicating that UTP, like ATP to a certain extent, produces relaxation via an endothelium nucleotide (N) pyrimidinoceptor. ATP, ADP, AMP, adenosine, 5'-N-ethylcarboxamidoadenosine (NECA) and inosine were all active as relaxants on smooth muscle. The NECA relaxant effect was not antagonized by P1-purinoceptor antagonists 3,7-dimethyl-1-propargylxanthine (50 microM) or 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (5 microM), excluding a P1-mediated effect. P2-related activity was excluded because adenosine-mediated relaxation was not antagonized by suramin (0.1 mM). UTP was ineffective as a relaxant at smooth muscle level, thus excluding the presence of muscular nucleotide (N) pyrimidinoceptor and suggesting a P3 purinoceptor. The rank order of potency of this muscle purinoceptor was NECA > adenosine > ATP approximately equal to ADP approximately equal to AMP approximately equal to inosine.

Adenosine↗
PubMed1994

Functional and morphologic characterization of thoracic aorta in heritable hyperlipidemic Yoshida rats of different ages.

We investigated serum and aortic tissue lipid content, in vitro aortic response to drugs, and morphology of thoracic aorta in Pittsburgh Yoshida rats (YOS), a new animal model of endogenous hyperlipidemia. Experiments were performed on 2-, 6-, and 18-month-old rats. Normolipidemic Brown Norway rats (BN) were used as controls. Both serum cholesterol and triglycerides increased significantly with age in YOS rats, but remained constantly low in the control group. In YOS rats, absolute serum concentration of high density lipoprotein (HDL)-cholesterol increased significantly with age, although HDL-cholesterol/total-cholesterol ratio decreased. In contrast, no difference in cholesterol content in aortic tissue was detected between the two animal strains or among different age groups. The contractile force generation of thoracic aorta to norepinephrine (NE) and serotonin increased with age in both strains of animals. The endothelium-dependent relaxation induced by acetylcholine (ACh) was significantly reduced in 6- and 18-month-old YOS as compared with 2-month-old YOS but not in BN. ATP-induced relaxation was significantly impaired in YOS thoracic aorta. In contrast, the relaxation induced by NaNO2 acting in smooth muscle did not vary with age in either YOS or BN. Only alterations in endothelial cells, not typical atheromatous injuries in thoracic aorta wall were detected in YOS even at age 18 months. Our data indicate that despite high serum lipid levels, YOS do not develop typical atheromatous lesions or functional and morphologic damage of smooth muscle cells in thoracic aorta, whereas YOS show decreased endothelium-dependent relaxation and morphologic alteration of endothelial cells.

Age Factors↗
PubMed1993

Species-dependent effects of increasing hypoxia on functions and energy balance in isolated atria.

1. The hypoxia-induced changes of contractile force, frequency and diastolic tension in isolated atria from guinea pig, rat and rabbit were studied together with tissue content of adenine nucleotides, creatine phosphate and lactic acid. 2. Increasing hypoxia induced a progressive reduction of contractility in guinea pig, rat and rabbit atria. Hypoxia also induced a progressive reduction of frequency in rat atria, whereas atrial rate decreased significantly only during drastic hypoxia in guinea pig and rabbit. In spontaneously beating atria, hypoxia increased diastolic tension only in rat. 3. After 30 min of drastic hypoxia, ATP decreased in guinea pig and rabbit but not in rat atria. Creatine phosphate decreased and lactic acid increased in all three species. 4. These data suggest that: (a) hypoxia-induced changes in atrial function and in metabolic content are species-dependent; (b) hypoxia-induced inhibition of atrial activity could represent protection aimed at saving energy.

Animals↗
PubMed1993

Atherosclerosis-related remodeling of aortic relaxation to purines in the Watanabe heritable hyperlipidemic rabbit.

The mechanism of the unimpaired relaxant effect of ATP in the Watanabe heritable hyperlipidemic rabbit aorta was investigated to elucidate the involvement of P2y purinoceptor at the endothelial level during atherosclerosis. Experiments were carried out on isolated thoracic aorta from such rabbits that were 12 months of age. The potent P2y purinoceptor agonist, 2-methylthio-ATP, did not induce any endothelium- or smooth muscle-dependent relaxation, thus excluding any involvement by the P2y purinoceptor. ADP, but not AMP, produced relaxation of the aorta by acting at both endothelial and smooth muscle levels. Adenosine relaxed the vessel by acting only in smooth muscle. The maintained endothelial relaxant effect of ATP and ADP is therefore not due to activation of P1 or P2y purinoceptors but may involve activation of a remodeled purinergic receptor site that emerges with the progression of atherosclerosis. This site is antagonized by methylene blue. The disorganization of the endothelial monolayer observed in the morphological analysis may be related to functional remodeling of the endothelial purinergic activity in atherosclerosis.

Adenine Nucleotides↗
PubMed1993

Technological testing of calcium carbonate tablets for use in the treatment of renal osteodystrophy.

Samples of calcium carbonate tablets produced by different manufacturers were subjected to various tests in order to evaluate tablet quality parameters, mostly indicative for calcium availability. Indications about tablet suitability for treatment of renal osteodystrophy in uremic patients were also tested. The disintegration test turned out to be the most useful in evaluating calcium carbonate availability from tablets. Samples from several manufacturers varied in their behaviour to disaggregation. The availability of calcium dissolved in gastric fluid and the extent of phosphorus binding appeared to depend on disintegration behaviour.

Calcium Carbonate↗
PubMed1992

Protective role of heparin on in vitro functional aortic response in Watanabe heritable hyperlipidemic rabbits.

The effects of prolonged in vivo heparin treatment upon vasomotor responses and content of cholesterol and energy related compounds were studied in isolated thoracic and abdominal aortas from Watanabe heritable hyperlipidemic (WHHL) rabbits. Unfractionated heparin was administered subcutaneously (2 mg/kg twice a day) to 3-month-old WHHL rabbits for a period of 6 months. A group of WHHL rabbits was treated with saline solution and considered as control. Aortic cholesterol infiltration and serum cholesterol were not significantly decreased by the prolonged heparin treatment. In heparin-treated WHHL rabbits, the in vitro aortic endothelium-dependent relaxation produced by acetylcholine or calcimycin (A 23187) was greater than in saline-treated WHHL group. ATP-induced aorta relaxation (endothelium-dependent and endothelium-independent) did not vary significantly in the two groups of WHHL rabbits, even after mechanical removal of endothelium. Also the noradrenaline-induced aorta contraction did not vary between the two groups of WHHL rabbits. No significant variation in energy-related compounds (except for ADP) was found in the aortic arch. These results suggest that heparin produces a protective effect on aortic tissue by acting mainly at endothelial level.

Adenosine Triphosphate↗
PubMed1992

Pharmacological characterization of ATP receptors mediating vasodilation on isolated rabbit aorta.

1. The effects of adenosine 5'-triphosphate (ATP), 2-methyl-thio-ATP and adenosine on rabbit aorta were examined in isolated preparations precontracted by noradrenaline, both in vessels where the endothelium was present and mechanically removed. 2. In the presence of endothelium, ATP (30 microM-3 mM) induced a relaxation that was reduced by removal of the endothelium. 3. The maximum endothelium-dependent relaxation of ATP was twice the maximum endothelial activity of the potent agonist at P2y-purinoceptors, 2-methyl-thio-ATP. 4. Adenosine which acts on P1 purinoceptors, induced a relaxant effect at 1 mM concentration, both in the vessels with and without endothelium. 5. It is concluded that relaxation by ATP is induced both via the endothelial P2y-purinoceptor and via a "nucleotide" receptor that is located on endothelium and on smooth muscle of rabbit aorta.

Adenosine↗
PubMed1992

Pharmacological characterization of a new purinergic receptor site in rabbit aorta.

1. The pharmacological properties of a vasodilating purine-activated receptor that is not a P1 or P2-purinoceptor were investigated. 2. In rabbit isolated thoracic aorta precontracted with noradrenaline, ATP induced a 50% relaxation at 0.25 mM (EC 50%); in the absence of endothelium, EC 50% was 2.5 mM. 3. Adenosine induced a relaxation that was not different in both the presence and absence of endothelium, being EC 50% 0.48 and 0.37 mM, respectively. 4. The potent and selective P2y-purinoceptor agonist 2-methylthio-ATP (0.03-10 microM) induced a relaxation only in the presence of endothelium. 5. In de-endothelialized aorta, 8-phenyltheophilline (8-PT: P1 antagonist) and 3,7-dimethyl-1-propargylxanthine (DMPX: A2 antagonist) did not antagonize ATP- and adenosine-induced relaxation. 6. The present data support the presence of a new site of action for purines in rabbit isolated thoracic aorta. 7. A P3 subtype of purinoceptor, that may be identified in the hypothesized "nucleotide" receptor, is proposed.

Adenosine↗
PubMed1992

Reduced L-arginine/lysine and L-arginine/aspartic acid ratios in aorta from Watanabe heritable hyperlipidaemic (WHHL) rabbit.

L-Arginine is the endogenous source of nitric oxide in the endothelial cells of blood vessels. In thoracic aorta from Watanabe heritable hyperlipidaemic (WHHL) rabbits, the L-arginine/lysine and L-arginine/aspartic acid ratios were reduced in comparison to New Zealand rabbit aorta. This result indicates that a variation in aortic arginine/lysine or arginine/aspartic acid ratios could be related to the hyperlipidaemic status.

Animals↗
PubMed1991

Aortic response to relaxing agents in Watanabe heritable hyperlipidemic (WHHL) rabbits of different age.

Serum and aortic tissue cholesterol levels in parallel with aortic relaxation to endothelium-dependent and independent drugs were determined in Watanabe heritable hyperlipidemic (WHHL) rabbits in comparison with New Zealand (N.Z.) normocholesterolemic rabbits, aged 4-14 months. Serum cholesterol was elevated (626 +/- 99 mg/100 ml) in 4-6-month-old WHHL rabbits and significantly lower in 12-14-month-old animals (344 +/- 51 mg/100 ml). Cholesterol infiltration in thoracic aorta was high in young WHHL compared with N.Z. rabbits (0.88 +/- 0.3 mg/100 mg fresh tissue vs. 0.08 +/- 0.003 mg/100 mg, respectively) and it did not vary with age. In N.Z. rabbits, serum and aortic cholesterol levels were low from 4 to 14 months of age. The aortic relaxation to acetylcholine (0.03-3 microM) on EC50 noradrenaline precontracted rings was similar in 4-6-month-old WHHL and N.Z. rabbits of the same age. In WHHL rabbits, the relaxation to acetylcholine was significantly reduced in 7-11- (-35% at maximum) and in 12-14-month-old rabbits (-40% at maximum). In N.Z. rabbits the response to acetylcholine was not modified in the 3 age groups. The relaxation to ATP (30 microM to 3 mM) was reduced by age both in N.Z. and in WHHL rabbits, but in 12-14-month-old WHHL rabbits the maximal relaxing response was significantly more elevated than in age-matched N.Z. rabbits (50.1 +/- 2.5% vs. 35.1 +/- 3.2%, respectively). The aortic relaxation to NaNO2 (10 microM to 3 mM) was reduced by age both in N.Z. and in WHHL rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1991

Adenosine: a natural modulator of L-type calcium channels in atrial myocardium?

The mechanism of action of adenosine at the level of atrial myocardium has been a matter of debate. Electrophysiological studies showed that adenosine increases K+ efflux which may reduce Ca2+ influx, indirectly, by shortening the myocardial action potential. Recently some authors proposed that adenosine also depresses Ca2+ influx by a direct action on the L calcium channel, but, this effect being lower than that on voltage-dependent K+ channels, it was considered of minor importance. The effect of adenosine and its stable analogues was studied in the presence of the dihydropyridine Bay K 8644, a highly specific L-type calcium channel agonist, on isolated guinea-pig atria. The inotropic effect of the calcium channel activator was found to be antagonized by adenosine A1-receptor agonists. Binding studies showed that the effect on Bay K 8644 was not due to the interaction between adenosine analogues and dihydropyridines at the level of a common receptor site on L-type Ca2+ channels. Inhibitors of K+ channels did not antagonize the effect of adenosine analogues against Bay K 8644. Experimental conditions aimed to unmask an effect on slow Ca2+ currents (i.e. K+ depolarized paced atria), further supported that adenosine analogues may act in atria as negative modulators on L-type Ca2+ channels. Finally, the use of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a highly specific A1-receptor antagonist, demonstrated that the antagonism of Bay K 8644 by adenosine analogues is strictly dependent on A1 receptors. The above data support the possibility of a dual signal transduction pathway to ion channels (K+ and Ca2+) linked to A1 receptors in atrial myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗