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Biomedical subjects

F Squadrito

Publications and source records attributed to F Squadrito.

At least 109 records · Page 6Linked to original sources
PubMed1992

IRFI-016, a new radical scavenger, limits ischemic damage following coronary artery occlusion in rats.

The effects of IRFI-016 [2(2,3 Dihydro-5-Acetoxy 4,6,7-Trimethyl-Benzofuranyl) acetic acid] a new radical scavenger were studied following six hours of myocardial ischemia, induced by left coronary artery occlusion in male rats. The loss of myocardial Creatinine Phosphokinase activity (CPK), myocardial Myeloperoxidase Activity (MPO), ECG, survival rate, and Pressure Rate Index (PRI) were evaluated in SHAM, control (vehicle i.p. injection) and IRFI-016 (200 mg/kg i.p., 30 minutes before occlusion) treated animals. CPK was significantly reduced and MPO significantly enhanced in the ischemic areas of the hearts obtained from vehicle treated rats when compared to SHAM operated ones. Pretreatment with IRFI-016 significantly attenuated (52%) loss of CPK activity in ischemic hearts and the increase in MPO activity, but did not increase PRI, thus indicating that this substance reduces the myocardial ischemic demand for oxygen. Occlusion of the coronary artery, furthermore, was associated with an immediate rise in the ST segment of the ECG, which was significantly attenuated by IRFI-016. These findings further support the important role of free radicals in the pathogenesis of acute myocardial ischemia and suggest that IRFI-016 may be a useful agent in the treatment of myocardial occlusion injury.

Animals↗
PubMed1991

Platelet activating factor involvement in splanchnic artery occlusion shock in rats.

Splanchnic artery occlusion shock was induced in anesthetized rats by clamping the splanchnic arteries for 45 min. The survival rate, plasma levels of thromboxane B2 (TxB2) and 6-keto-PGF1 alpha, serum and peritoneal levels of macrophage tumor necrosis factor (TNF alpha), the phagocytotic and killing activity of peritoneal macrophages and white blood cells count were evaluated. Shocked rats died within 2 h, while all sham-shocked rats survived more than 6 h. Plasma TxB2 and 6-keto-PGF1 alpha levels were increased in rats subjected to splanchnic artery occlusion shock compared to the levels in sham-shocked animals. Serum and peritoneal macrophage TNF alpha levels were undetectable in sham-shocked rats, whereas shocked rats exhibited increased levels of TNF alpha. Moreover, splanchnic artery occlusion shock reduced peritoneal macrophage phagocytotic and killing activity, and also produced severe leukopenia. A specific receptor antagonist of platelet activating factor (PAF), L-652, 731 (an i.v. bolus of 3.2 mg/kg 2 min after removal of the clamps followed, 5 min thereafter, by a continuous infusion of 0.16 mg/kg per min for 30 min) significantly increased the survival rate, lowered plasma TxB2 levels and reduced both serum and macrophage TNF alpha levels in shocked rats. In addition, L-652,731 completely restored macrophage phagocytosis, partially improved macrophage killing and significantly inhibited leukopenia. Finally, the administration of L-652,731 had beneficial effects on the cardiovascular changes induced by splanchnic artery occlusion shock. These findings are consistent with the involvement of PAF in splanchnic artery occlusion shock and indicate that PAF produces shock through direct and indirect (TxB2-mediated and TNF alpha-mediated) actions.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Protective effect of cloricromene, a coumarine derivative, in hypovolemic hemorrhagic shock in the rat.

Hypovolemic hemorrhagic shock was induced in male anesthetized rats by intermittently withdrawing blood from an iliac catheter over a period of 20 min until mean arterial pressure (MAP) fell to 30 mm Hg. Survival rate, MAP, plasma myocardial depressant factor (MDF) activity and plasma levels of both TxB2 and 6-keto PGF1 alpha were then evaluated. Cloricromene (0.5, 1, and 2 mg/kg) or an equal volume of vehicle (0.9% NaCl solution) were injected intravenously 5 min after the end of the bleeding. Hemorrhagic shocked rats showed enhanced plasma levels of MDF, TxB2 and 6-keto PGF1 alpha. All vehicle-treated rats died within 25 min. Cloricromene (1 and 2 mg/kg) given curatively significantly increased survival rate and blunted the rise in plasma MDF and TxB2. Moreover, cloricromene reversed the severe hypotension and the ST-segment elevation occurring during hemorrhagic shock. The data suggest that cloricromene exerts beneficial effects in experimental hypovolemic shock, probably reversing myocardial failure.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Antihypertensive activity of indolepyruvic acid: a keto analogue of tryptophan.

We studied the effect of indole-3-pyruvic acid (IPA) on systolic blood pressure of normotensive, spontaneously hypertensive, DOCA + salt hypertensive, and Grollman hypertensive rats. Experiments were also carried out in order to investigate whether IPA may influence the development of hypertension in spontaneously hypertensive rats. Age-matched normotensive, spontaneously hypertensive, DOCA + salt hypertensive, and Grollman hypertensive rats treated with N-methylglucamine, were used as controls. Acute oral (up to 50 mg/kg) and intravenous (5 mg/kg) administration of IPA did not change systolic blood pressure in any models of hypertension. By contrast, a repeated administration of IPA (100 mg/kg/day, by oral gavage for 10 days) significantly decreased systolic blood pressure in all models of hypertension, while it elicited no significant effect in normotensive rats. Moreover, when IPA was given daily to 5-week-old spontaneously hypertensive rats for 7 weeks, it partially inhibited the development of hypertension. In addition, chronic administration of IPA caused enhanced levels of tryptophan and 5-hydroxyindoleacetic acid in the cortex and diencephalon. Brainstem serotonin content in both normotensive and spontaneously hypertensive rats was also enhanced by IPA treatment. Our results suggest that IPA lowers blood pressure in different rat models of hypertension and this effect seems to be correlated with an increase in cerebral serotonin metabolism.

Animals↗
PubMed1990

Effects of intracerebroventricular administration of magnesium sulphate on blood pressure and heart rate in anesthetized normotensive and hypertensive rats.

Intracerebroventricular (i.c.v.) injection of magnesium sulphate (MgSO4:2.5, 5 and 10 mumol in 5 microliters) decreased blood pressure and heart rate in both anesthetized normotensive (WKY) and hypertensive rats (SHR). The effects were greater in WKY than in SHR. Moreover, a pretreatment with hexamethonium (2 mg/kg, i.v.) significantly blunted the hypotensive and bradycardic effects induced by i.c.v. injection of 10 mumol of MgSO4 in both WKY and SHR. Our data suggest that MgSO4 produces hypotensive and bradycardic effects when injected i.c.v. in both WKY and SHR.

Anesthesia↗
PubMed1989

Effects of fructose 1,6-diphosphate on splanchnic artery occlusion shock in the rat.

Splanchnic artery occlusion (SAO) shock, produced by clamping splanchnic arteries for 45 min followed by the release of occlusion, was induced in male rats, treated 15 min before surgery, with fructose 1,6-diphosphate (FDP) or with equivalent doses of fructose or inorganic phosphate. Survival rate, peritoneal macrophage phagocytosis and plasma levels of myocardial depressant factor (MDF) were measured. Shocked animals pretreated with vehicle exhibited 24.6 +/- 0.9% phagocytic activity, 110 +/- 3.9 units/ml MDF plasma levels and 0% survival. Sham animals showed the following values: survival 100%; phagocytosis, 49.5 +/- 1.3%; MDF, 22 +/- 2.9 units/ml. Pretreatment with FDP (25 mg/kg/i.v.) significantly improved survival rate (50%) and macrophage phagocytosis (37.9 +/- 0.4%) and reduced plasma MDF levels (77 +/- 3 units/ml). Equivalent doses of fructose and inorganic phosphate did not improve survival, as well as lower doses of FDP. These results suggest a beneficial effect of FDP in SAO shock.

Animals↗
PubMed1989

A comparison of synthetic human and rat ANP administered intracerebroventricularly in freely moving normotensive and hypertensive rats.

The effects of intracerebroventricular (i.c.v.) injection of alpha-human atrial natriuretic peptide (alpha-hANP) and alpha-rat atrial natriuretic peptide (alpha-rANP) were studied in normotensive [Wistar-Kyoto (WKY)] and spontaneously hypertensive rats (SHR). Intracerebroventricular injection of alpha-hANP (200, 400, and 800 ng in 5 microliters) did not modify mean arterial pressure (MAP), heart rate (HR), and water intake in both WKY rats and SHR. On the contrary, alpha-rANP (200, 400, and 800 ng in 5 microliters) caused strong dipsogenic, pressor, and bradycardic effects that were greater in hypertensive than in normotensive rats. Saralasin (9 microns in 5 microliters), injected 2 min prior to alpha-rANP, abated these effects, thus indicating an involvement of brain angiotensin. Our results suggest that, at least as far as the cerebral effects of ANP are concerned, some difference exists between alpha-rANP and human atrial natriuretic peptide.

Animals↗
PubMed1989

Effects of calmodulin and calcium channel blockers on the Ca2+ induced outflow of K+ in intact red blood cells of patients with essential hypertension.

The correlation between the alterations of free intracellular calcium concentrations and the essential arterial hypertension has been largely investigated. Calmodulin, a cytoplasmic protein with low molecular weight, is one of the factors known to be able to affect the activity of calcium-dependent enzymes. The authors have investigated the effect of calcium and calmodulin on the plasmatic membrane of intact erythrocytes in a group of patients with essential arterial hypertension. To this purpose, the ionophor A23187, propranolol at low concentrations and a few calcium channel blocking drugs, alone or associated with calmodulin have been used. The results demonstrate that calmodulin, capable of blocking calcium outside the cell, can exert its effect only when propranolol is also present in the erythrocytes of normotensive but not in the hypertensive patients. The authors discuss some pathogenetic hypotheses.

Adult↗
PubMed1989

Cloricromene improves survival rate and peritoneal macrophage function in splanchnic artery occlusion shock in rats.

Splanchnic artery occlusion (SAO) shock, induced by a transient occlusion of splanchnic arteries for 45 min, was performed in male rats, treated with vehicle or cloricromene, a coumarin derivative, 15 min before surgery. Survival rate, plasma levels of myocardial depressant factor (MDF), macrophage phagocytosis and killing of Candida albicans, and thromboxane B2 (TxB2) synthesis by peritoneal macrophages were evaluated. Of the SAO-shocked animals, 10% survived for 6 hr after the release of the occlusion of the splanchnic arteries, whereas none of the sham-shocked rats died. Peritoneal macrophages of shocked animals exhibited decreased phagocytosis (24.7 +/- 2.7%) and killing (8.0 +/- 2.1%) and increased TxB2 levels (3.23 +/- 0.27 ng/ml) with respect to those collected from sham-shocked animals (phagocytosis 48.8 +/- 3.0%; killing 16.5 +/- 2.4%; TxB2 0.30 +/- 0.18 ng/ml). MDF was also increased (114.3 +/- 21.5 U/ml) compared with sham-shocked animals (31.5 +/- 3.7 U/ml). Cloricromene, given intravenously (i.v.) at doses of 1, 2, and 4 mg/kg, significantly increased survival rate and lowered MDF in shocked rats. Lower doses (0.25 and 0.5 mg/kg/i.v.) were without effect. Doses that were able to reduce mortality partially reverted shock-induced macrophage impairment of phagocytosis, killing of C. albicans, and TxB2 synthesis. In addition, cloricromene (5, 10, and 25 microM) added in vitro to peritoneal macrophages, collected from shocked rats, significantly enhanced their phagocytic activity depressed by shock.

Animals↗
PubMed1988

Splanchnic artery occlusion shock in the rat: effects of the calcium entry blockers nimodipine and verapamil.

Splanchnic artery occlusion (SAO) shock made by clamping splanchnic arteries for 45 min was performed in female rats infused for 30 min with vehicle, nimodipine, and verapamil before, during, or after SAO. Survival time, macrophage phagocytosis and killing, and white cell count were evaluated in conscious rats. Shocked animals pretreated with vehicle exhibited 24.6 +/- 0.9% phagocytic activity, 5.1 +/- 0.7% killing activity, and survived 177 +/- 1.7 min. Leukopenia was also present. Sham animals survived more than 300 min, and showed the following values: phagocytosis = 52.8 +/- 0.6%, killing = 18.8 +/- 0.6%. Pretreatment with nimodipine (1 microgram/kg/min x 30 min, intravenously [IV]) before SAO significantly prolonged survival time (274 +/- 4.7 min) and improved phagocytosis (38.1 +/- 0.6%) and killing (16.1 +/- 1.1%), but did not change leukopenia. Lower doses of nimodipine (0.25 and 0.5 microgram/kg/min x 30 min, IV), and all the doses of verapamil (100 and 200 micrograms/kg/min x 30 min, IV), when infused before SAO, were ineffective. Neither nimodipine nor verapamil, when infused for 30 min either during or immediately after SAO, were able to influence survival, macrophage functions, or white cell count. Moreover, nimodipine (5, 10, and 25 microM), when added "in vitro" to macrophages collected from SAO-shocked rats, significantly enhanced their phagocytic activity, while verapamil (100 and 200 microM) did not change it. Finally, in anaesthetized rats nimodipine pretreatment had a beneficial effect on the cardiovascular changes occurring during SAO shock. These data suggest that nimodipine has a beneficial effect in SAO-shocked rats only when given before SAO.

Animals↗
PubMed1987

Human alpha atrial natriuretic peptide inhibits angiotensin stimulated aldosterone biosynthesis in bovine adrenal glands.

The behaviour of aldosterone output was evaluated in isolated and superfused bovine adrenal glands during superfusion with human alpha atrial natriuretic peptide on its own or with angiotensin II or a antagonist dopaminergic drug: metoclopramide. H alpha-ANP even in high concentrations did not reduce the basal amount of aldosterone released from bovine adrenal glands, nor did it modify aldosterone response to metoclopramide, but it partially inhibited aldosterone stimulation by angiotensin II. These data suggest that atrial natriuretic factor may affect sodium secretion through the modulation of aldosterone secretion.

Adrenal Glands↗
PubMed1987

Central dipsogenic effect of synthetic rat atrial natriuretic polypeptide in normotensive rats.

The effect of intracerebroventricular (i.c.v.) injection of synthetic rat atrial natriuretic polypeptide (alpha-rANP) on drinking behavior was studied in normotensive rats, alpha-rANP (0.2, 0.4 or 0.8 micrograms in 5 microliter) caused a dose-dependent dipsogenic effect which was abated by i.c.v. pretreatment with saralasine (9 micrograms in 5 microliter). These results suggest that alpha-rANP possesses dipsogenic effects in water repleted rats and that brain angiotensin is involved. In addition, our data indicate that, at least as far as the effect of cerebral ANP is concerned, there are some differences between alpha-rANP and human atrial natriuretic polypeptide.

Animals↗
PubMed1987

Cerebral GABAergic control of arterial blood pressure and heart rate in diabetic rats.

Cardiovascular responsiveness to intracerebroventricular (icv) administration of dopamine (50, 100 and 200 micrograms/kg), muscimol (1 and 2 micrograms), and ethanolamine-O-sulphate (EOS; 5, 10, 20 and 40 mumol) as well as GABA content in several brain areas were examined in rats, made diabetic by an intravenous (iv) injection of streptozotocin (STZ; 40 mg/Kg). Citrate buffer (pH 4.5) treated animals were used as controls. Experiments were carried out in conscious rats with chronically implanted icv cannulae and iv and intraarterial catheters, 1 and 3 weeks after STZ injection. Diabetic rats exhibited: 1) higher hyperglicaemia after 1 week than after 3 weeks; 2) normal mean arterial pressure (MAP) both after 1 and 3 weeks, and 3) bradycardia only after 3 weeks. Icv injections of muscimol, a GABA receptor agonist, and EOS, an inhibitor of GABA breakdown, caused a dose-dependent decrease in MAP and heart rate (HR), which was significantly higher than that elicited in control animals. GABA content was reduced in the hypothalamus (already after 1 week), and in the brainstem (but only after 3 weeks). No changes in GABA content were detected in other brain areas. Icv injection of dopamine elicited a dose dependent decrease in MAP and HR either in diabetic or in control rats, with no difference between groups. The results suggest that diabetes alters cerebral GABAergic control of arterial blood pressure and heart rate in the rat.

Animals↗
PubMed1986

Cerebral cholinergic control of rat arterial blood pressure in streptozotocin-induced diabetes.

Rats were made diabetic with a single intravenous injection of streptozotocin (STZ; 40 mg/Kg). Buffer treated animals were used as controls. Experiments were performed 7 and 14 days thereafter. One week diabetic rats (plasma glucose = 3.34 +/- 0.58 mg/ml), compared with control animals (plasma glucose = 0.94 +/- 0.33 mg/ml), showed higher (P less than 0.05), more prolonged and dose-dependent pressor and bradycardic responses to intracerebroventricular (icv) injection of carbachol (125, 250 and 500 ng), together with a significantly lower bradycardia after icv injection of physostigmine (1.25, 2.5 and 5 mcg). The pressor response to icv injection of physostigmine (1.25 mcg) was significantly reduced in diabetic rats. Pressor and bradycardic responses induced by angiotensin II (100 and 200 ng, icv) did not show any differences between control and diabetic animals, thus ruling out an impairment of peripheral nerve conduction. Diabetic rats exhibited higher content of acetylcholine (Ach) in the striatum (123.8 +/- 3.09 nmoles/g) and in the hypothalamus (45.7 +/- 1.31 nmoles/g). Three weeks diabetic animals (plasma glucose = 2.76 +/- 0.23 mg/ml) had neither different cardiovascular responsiveness to icv injection of muscarinic agonists nor changes in hypothalamus and striatum Ach content. Data strongly suggest that STZ-induced diabetes temporarily alters cerebral acetylcholine control of cardiovascular apparatus.

Angiotensin II↗