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B Battistini

Publications and source records attributed to B Battistini.

71 records · Page 4Linked to original sources
PubMed1991

A role for Na+/H+ exchange in contraction of guinea pig airways by endothelin-1 in vitro.

Endothelin-1-induced contractions of guinea pig tracheal and bronchial strips were dose-dependently attenuated by the amiloride analogues 5-(N-ethyl-N-isopropyl)amiloride (EIPA, 1-10 microM) and 5-(N,N-hexamethylene)amiloride (HMA, 1-10 microM). The calculated Ki values for EIPA and HMA were 0.11 +/- 0.02 microM and 0.06 +/- 0.02 microM in the trachea, and 0.28 +/- 0.11 microM and 0.70 +/- 0.25 microM in the bronchus, respectively. These values are in the same order of magnitude as those reported for inhibition of the Na+/H+ exchange in cells. Amiloride (1-10 microM) was ineffective. These data suggest that activation of the Na+/H+ exchange by ET-1 may be involved in mediating its myotropic action in guinea pig airway smooth muscle.

Amiloride↗
PubMed1991

Antiaggregatory and hypotensive effects of endothelin-1 in beagle dogs: role for prostacyclin.

The effects of endothelin-1 (ET-1) on blood pressure and platelet aggregation were studied in anesthetized beagle dogs. Platelet aggregation was monitored in vivo by a filter-loop technique and in vitro by using platelet-rich plasma and whole blood. ET-1 (0.03-0.3 nmol/kg) induced a transient dose-dependent hypotension and inhibited platelet aggregation in vivo. These changes were accompanied by dose-dependent elevation of plasma 6-keto-PGF1 alpha levels. Pretreatment of animals with indomethacin (2 mg/kg plus 3 mg/kg/h) completely abolished the antiaggregatory action of ET-1 and significantly attenuated the hypotensive response to ET-1. Intra-arterial infusion of prostacyclin at concentrations similar to those observed following ET-1 injections mimicked the antiaggregatory and hypotensive actions of ET-1. ET-1 (0.1-100 nM) did not modify platelet aggregation induced by ADP, collagen, and platelet-activating factor in vitro, suggesting that dog platelets do not possess ET-1 receptors. These findings indicate that the antiaggregatory and hypotensive actions of ET-1 in beagle dogs are mediated through release of prostacyclin.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Pharmacological modulation of endothelin-induced contraction of guinea-pig isolated airways and thromboxane release.

1. The aim of the present experiments was to study the possible involvement of known bronchoconstrictor substances in mediating the myotropic action of endothelin-1 (ET-1, human-porcine endothelin) in guinea-pig isolated airways. 2. ET-1 (1-100 nM) caused a dose-dependent contraction of guinea-pig trachea, upper bronchus and parenchyma. The contractions developed slowly, reaching maximal values 4-6 min after addition of the peptide. 3. The contractile action of ET-1 was significantly attenuated by indomethacin (10 microM), a cyclo-oxygenase blocker. BM 13505 (5 microM), a thromboxane receptor antagonist, FPL 55712 (19 microM) and YM 16638 (1 microM), antagonists of the sulphidopeptide leukotrienes, BN 52021 (10 microM) and WEB 2086 (1 microM), platelet-activating factor receptor antagonists in all three tissue preparations studied. 4. Pretreatment of the airway tissues with compound U 75302 (3 microM), a selective leukotriene B4 receptor antagonist, or with a mixture of antagonists containing methysergide (0.75 microM), phentolamine (0.4 microM), propranolol (13 microM), atropine (0.4 microM) and diphenhydramine (0.45 microM) did not modify the myotropic action of ET-1. 5. ET-1, 10 and 100 nM induced three, and nine fold increases in thromboxane A2 release from lung parenchymal strips. 6. ET-1-induced thromboxane A2 release was completely abolished by indomethacin, and was significantly attenuated by BN 52021, WEB 2086 and FPL 55712. Neither BM 13505 nor YM 16638 exerted a significant effect on thromboxane release. 7. The present findings show that contraction of guinea-pig airway smooth muscle by ET-1 is mediated, in part, by the release of thromboxane A2, sulphidopeptide leukotrienes and platelet-activating factor, and suggest that the increased thromboxane A2 release following ET-1 is partly a consequence of enhanced synthesis of sulphidopeptide leukotrienes and platelet-activating factor.

Animals↗
PubMed1990

Endothelin-induced constriction of guinea pig airways: role of platelet-activating factor.

Endothelin-1 (ET-1, 1-100 nM) evoked a concentration-dependent contraction of guinea pig trachea and upper bronchi in vitro. The response was significantly attenuated by BN 52021 (ginkgolide B, 10 microM), a specific receptor antagonist to platelet-activating factor. Precontraction of the tissues with endothelin (50 nM) desensitized tissues to platelet-activating factor (200 nM), while preincubation of the tissues with platelet-activating factor slightly inhibited the response to endothelin. These findings suggest that platelet-activating factor may mediate endothelin-induced airway contraction in the guinea pig.

Animals↗
PubMed1990

Endothelin induces thromboxane release and contraction of isolated guinea-pig airways.

The possible role of thromboxane (TX) A2 in mediating the bronchopulmonary effect of endothelin (ET) was studied in isolated guinea pig airways (trachea, upper bronchi and parenchyma). ET (1-100 nM) evoked a concentration-dependent contraction of all three tissues. The contractile response was significantly attenuated by pretreatment of the tissues with the specific thromboxane receptor blockers, BM 13177 (10-50 microM) and BM 13505 (1-5 microM). Furthermore, ET caused a dose-dependent TXB2 release from trachea and parenchyma. These findings suggest that the bronchopulmonary action of ET is mediated, in part, by the release of TXA2.

Animals↗
PubMed1990

Secretion of gamma-glutamyltranspeptidase by the pancreas: evidence for a membrane shedding process during exocytosis.

Gamma Glutamyltranspeptidase (GGT) is a membrane-bound enzyme involved in glutathione metabolism. It is present in rat exocrine pancreas at a level which is only exceeded by the kidney. It has been previously shown that most of the enzyme activity is located in the apical area of the acinar cell, more precisely at the level of zymogen granules and plasma membrane. The aim of the present study was to examine the secretory behavior of that enzyme. Under resting conditions, in vivo, high levels of GGT were found in pancreatic juice and its level was not related to protein concentration. Under secretin infusion, a relatively constant level of GGT was released, and again, there was no correlation between enzyme activity and protein concentration. Following a bolus injection of caerulein, an analog of cholecystokinin, marked and concomitant rises in protein and GGT levels were observed. Ultracentrifugation, as well as gel filtration on Sepharose 4B, demonstrated that the enzyme was not released in a soluble form. This observation is in agreement with in vitro determinations on isolated zymogen granules showing that GGT is totally associated with the ZG membrane and undetect-able in the content of these organelles. The present data show that 1 degree GGT is released from the rat pancreas acinar cells in a particulate form; 2 degree GGT release is elicited by hormonal stimulation coinciding with the exocytotic release of secretory proteins. Our observations lead us to propose that in rat pancreas, ZG membrane fragments are released along with secretory proteins during exocytosis.

Animals↗
PubMedDate not supplied

Roles of endothelins and their receptors in immune complex-induced/polymorphonuclear-mediated lung injury (reversed passive arthus reaction) in CD-1 mice.

A number of pro-inflammatory mediators (leukotrienes, platelet activating factor, cytokines) participate in the process of neutrophil-dependent lung injury induced by immune complexes. Here, we studied the role of endothelins (ET) in the reversed passive Arthus reaction (AR) as a model of pneumonitis in CD-1 mice. We examined the broncholaveolar lavage fluid (BALF) for signs of inflammation such as the accumulation of cells, myeloperoxidase (MPO) activity and hemoglobin (Hb) levels, as a measure of hemorrhagic lesions, 24 h after injection. We used a selective ETA (BQ-123) or a non-selective ETA/ETB-R (SB 209670) receptor antagonist at various concentrations (2.5, 5 or 10 mg/kg ip at -8, 0, 8 and 16 h) to assess the involvement of ET. Challenged mice revealed signs of acute inflammation and hemorrhagic lesions. Levels of Hb and MPO, total and neutrophil cell counts increased by 9-, 9-, 3.2- and 63-fold, respectively. The lower dose of SB 209670 reduced Hb levels by 21% (P<0.05), without affecting cell accumulation or MPO. The mid-dose had no effect; the highest dose caused 60, 57 and 70% increases in Hb levels, total cell and neutrophil counts, respectively. Conversely, the highest dose of BQ-123 decreased Hb, total cell and neutrophil counts and MPO levels by 36, 35, 42 and 70%, respectively. These results support a role for ET in AR lung injuries. They also suggests that blocking ETA-R may be beneficial, while blockade of ETB-R (using a high dose of SB 209670) may be detrimental. A beneficial ETB-mediated response may exist that naturally interferes with events triggered by the formation of immune complexes such as cell accumulation and their subsequent activation leading to acute lung injury.

Animals↗
PubMedDate not supplied

Adenosine-induced inhibition of basal endothelin-1 production from guinea-pig tracheal epithelial cells: a mechanism involving the release of cAMP.

Guinea-pig tracheal epithelial cells, like other pulmonary cells in various species, have been reported to synthesize and release endothelins (ET). Their production is inducible by many agents and inhibited by ET-converting enzyme inhibitors, corticosteroids and beta agonists. Here, we studied the effect of adenosine on (1) the formation of adenosine 3', 5'-cyclic monophosphate (cAMP) and (2) concomitant effect on the basal release of ET from primary cultured tracheal epithelial cells isolated from guinea-pigs (GPTEpC). Adenosine (10(-7)-10(-3) M), the endogenous non-selective purinergic receptor agonist, induced the production of cAMP in a concentration-dependent manner (pD2=4.99+/-0.09). Concomitantly, adenosine decreased by a maximum of 39% ET-1-production over the same concentration range (with a 96% correlation). The inhibitory effect over ET-1-production was abolished by CGS15943 (10(-4) M), a non-selective A1/A2A receptor antagonist, and a xanthine amine congener (10(-4) M), a selective A1 receptor antagonist. Thus, these results suggest that adenosine attenuates the production of ET-1 from GPTEpC by stimulating the release of cAMP via the direct activation of adenosine receptors.

Adenosine↗
PubMedDate not supplied

Growth regulatory properties of endothelins.

Endothelins are produced by endothelial and epithelial cells, macrophages, fibroblasts, and many other types of cells. Their receptors are present in numerous cells, including smooth muscle cells, myocytes, and fibroblasts. Evidence now suggests that the three isoforms of endothelins (ET-1 and the other two related isopeptides, ET-2 and ET-3) regulate growth in several of these cells. Endothelin-1 influences DNA synthesis, the expression of protooncogenes, cell proliferation, and hypertrophy. The participation of ET in mitogenesis involves activation of multiple transduction pathways, such as the production of second messengers, the release of intracellular pools of calcium, and influx of extracellular calcium. Moreover, ET-1 acts in synergism with various factors, such as EGF, PDGF, bFGF, TGFs, insulin, etc., to potentiate cellular transformation or replication. Several of these factors may in turn stimulate the synthesis and/or the release of endothelins. The production and release of endothelins are also increased in acute and chronic pathological processes, e.g., atherosclerosis, postangioplastic restenosis, hypertension, and carcinogenesis. It is postulated that endothelins act in a paracrine/autocrine manner in growth regulation and play an important role mediating vascular remodeling in some cardiovascular diseases. The present review analyses the implication of endothelins (ET-1, -2, and -3) in physiopathology related to their growth regulatory properties.

Animals↗
PubMedDate not supplied

Endothelin derivatives showing potent effects in the guinea pig trachea.

Endothelin (ET-1) was synthesized by solid-phase peptide synthesis. To prevent side reactions with tryptophan residue, a formyl group was used to protect the beta-indole moiety. The two disulfide bridges were formed selectively using S-methylbenzyl for the cysteine residues in positions 3 and 11, and S-acetamidomethyl for positions 1 and 15. Crude synthetic ET-1 was obtained after deprotection and cleavage from the resin by HF, followed respectively by potassium ferricyanide and iodine oxidations, in order to generate sequentially the monocyclic and bicyclic forms of the peptide. Finally, Trp(For) was deprotected by a treatment with piperidine. After each step, a sample of peptide was isolated and purified by RP-HPLC. The biological activity of these synthetic peptides was evaluated on guinea pig tracheal strips. The results suggest that oxidation of Met-7 and/or formylation of Trp-21 do not affect the biological activity of ET-1 in the guinea pig trachea. Moreover, although a decrease of potency and intrinsic activity was observed, the monocyclic analog containing Cys(Acm) residues at positions 1 and 15 exhibited substantial constrictor activity. This result, contrasting with that observed with several vascular preparations, suggests that the guinea pig trachea contains a distinct ET receptor population.

Animals↗
PubMedDate not supplied

A novel procedure for daily measurements of hemodynamical, hematological, and biochemical parameters in conscious unrestrained rats.

Accurate and chronic measurements of various parameters in conscious animals are fundamental for depicting pathological chronic conditions and their etiology in many experimental models, but they are often difficult to achieve. The aim of the present work was to develop and describe step-by-step a reproducible surgical procedure and daily manipulations for continuous, chronic use of conscious rats as models towards a better understanding of various cardiovascular and renal diseases and the testing of novel pharmacological drugs. The complete apparatus involved the use of a series of specialized devices (harness, rotating swivel, revolving arm) supporting a flexible, permanently implanted vascular catheter into the left femoral artery up to the abdominal aorta connected to a miniaturized individual peristaltic pump for delivering fluid at a constant rate. Such a set-up also enabled easy, quick, and reproducible daily blood sampling for the evaluation of more than 20 parameters, including the monitoring of heart rate (HR) and blood pressure in freely moving conscious rats. The overall success and survival rate reached 98% over 14 days and could be extended further. This model represents a much needed and valuable advance in surgical research techniques to evaluate the hemodynamic, hematological, biochemical, pharmacokinetic, and toxicological profile of any new drugs over time in conscious animal models such as rats. What makes this procedure satisfactory is the long-term reliable arterial access and reproducibility of the methodological approach for accurate and continuous measurements, minimizing the stress or invasiveness associated with the use of currently employed systems.

Animals↗
PubMedDate not supplied

The many aspects of endothelins in ischemia-reperfusion injury: emergence of a key mediator.

The endothelins (ETs) are regulatory peptides, distributed in many organ systems and producing potent physiological effects. They are the most powerful vasoconstrictive substances known today. They also act as promitogens. Many data supporting pathophysiological roles for ETs are reported, especially regarding diseases related to the vascular system, such as hypertension, pulmonary hypertension, preeclampsia, ischemic heart diseases, renal failure, subarachnoidal hemorrhage, and cerebral ischemia. The development of drugs blocking ET binding to its receptors (antagonists) and the biosynthesis of ETs (ECE inhibitors) presently attracts great interest in terms of establishing new treatments for diseases in which ETs are believed to be involved. Here we review the evidence supporting a role for ETs in the various etiologies related to ischemia-reperfusion injury, such as is found in heart disease, cerebral ischemia, and organ transplantation.

Animals↗