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Biomedical subjects

R Scivoletto

Publications and source records attributed to R Scivoletto.

At least 37 records · Page 2Linked to original sources
PubMed1989

Functional changes in the microcirculation of alloxan-induced diabetic rats.

1. The constrictor response of microvessels to norepinephrine and tyramine, and the dilator response to acetylcholine and papaverine was equivalent in normal and alloxan-induced diabetic rats. 2. Acetylcholine and phentolamine were equally effective as antagonists of the vasoconstrictor action of norepinephrine in both groups of animals. 3. The minimum effective doses of histamine and PAF-acether to produce maximum dilation of microvessels, or to antagonize the response to norepinephrine in normal rats had to be increased 20-fold to evoke equivalent effects in diabetic animals.

Acetylcholine↗
PubMed1989

Chronic but not acute treatment with hydralazine reverses the decreased endothelium-dependent responses in spontaneously hypertensive rats.

The relaxant response to acetylcholine (ACh) an endothelium dependent vasodilator agent and sodium nitroprusside (SNP), an endothelium independent vasodilator agent, of precontracted isolated aortae and mesenteric arterioles in vivo-in situ were studied in spontaneously hypertensive rats (SHR) and normotensive Wistar rats treated with hydralazine in acute (24 h) and chronic (15 d) administration. The impaired responses to ACh observed in SHR vessels were restored by chronic but not by acute treatment, whereas the SNP-induced responses were not affected. It is suggested that: 1) The acute decrease of blood pressure level per se is not sufficient to restore the impaired response to ACh; 2) The alteration of vascular response is not an irreversible phenomenon; 3) Hydralazine did not interfere with the relaxant responses to SNP.

Acetylcholine↗
PubMed1989

The role of endothelium in vascular reactivity.

1. This review describes the role of vascular endothelium in the response induced by different vasoactive agents. 2. The interaction between endothelium, vascular smooth muscle and platelets is discussed. 3. The hormone control as well as physicochemical alterations that interfere with some endothelium-dependent vascular responses are described.

Acetylcholine↗
PubMed1988

Reactivity of macro- and microvessels of DOCA-salt hypertensive rats: role of the endothelial cell.

The responses to noradrenaline (NA) and acetylcholine (ACh) of aortae and microvessels were compared in control and DOCA-salt hypertensive rats. Macro- and microvessels from hypertensive rats showed an increased response to NA and a decreased response to ACh (an endothelium-dependent vasodilator). Unlike ACh, sodium nitroprusside (an endothelium-independent agent), was equally effective in evoking a vasodilator response from aortae and microvessels of hypertensive rats. These data suggest that the impaired response to ACh and the increased response to NA in DOCA-salt hypertension may result from an alteration of endothelial cell function.

Acetylcholine↗
PubMed1987

Reactivity of aorta and mesenteric microvessels to drugs in spontaneously hypertensive rats: role of the endothelium.

The response to vasoactive agents of microvessels in situ and aortae in vitro was studied in normal and spontaneously hypertensive rats (SHR). Noradrenaline (NA) was equally effective in evoking a constrictor response of mesenteric microvessels in normal rats and SHR. The vasodilator response to acetylcholine (ACH), as endothelium-dependent relaxing agent, was lower in SHR microvessels whereas isoproterenol, papaverine, agents which are partially dependent on endothelium, and sodium nitroprusside, an endothelium-independent vasodilator, induced similar responses in control rats and SHR. Median effective concentrations and maximal responses to NA obtained in isolated SHR aortae, with or without endothelium, were similar to those obtained in their respective controls. NA-precontracted aortae with intact endothelium were less responsive to ACH in SHR than in controls. The relaxant response of the preparations was lost after endothelial cell removal in both groups. Sodium nitroprusside evoked similar relaxing effect in SHR and control NA-precontracted aortae. Isoproterenol-induced responses were potentiated in SHR-precontracted aortae, with or without endothelium. Removal of the endothelium diminished isoproterenol-induced relaxation, both in controls and SHR. With submaximal concentration of papaverine there was no difference between SHR aortae with or without endothelium and control aortae with endothelium. Control aortae without endothelium relaxed less than control aortae with endothelium and SHR aortae with or without endothelium. The rate of relaxation after papaverine was altered in aortae without endothelium isolated from SHR or control rats. These results indicate that the endothelium of SHR is altered. This could explain its decreased response to ACH. It is suggested that smooth muscle cells develop a compensatory mechanism that increases the response of agents that mobilize cAMP, such as papaverine and isoproterenol.

Acetylcholine↗
PubMed1986

Thyroid hormones and vascular reactivity: role of the endothelial cell.

Decreased maximal responses to noradrenaline, adrenaline and phenylephrine were observed in aortas isolated from rats pretreated with triiodothyronine and thyroxine for 8 days. In addition, a potent relaxant effect occurred when supramaximal concentrations of noradrenaline and adrenaline, but not of phenylephrine, were used. The relaxant effect was not observed in preparations in which the endothelium had been removed, and it was antagonized by propranolol added to the bathing fluid. Practolol was ineffective. In vivo, adrenaline and noradrenaline evoked pressor effects which were of shorter duration and smaller magnitude in hormone-treated animals than in the controls. Furthermore, a subsequent fall in blood pressure to below normal was observed, not only with adrenaline but also with noradrenaline, in animals receiving thyroid hormones. We conclude that when large amounts of thyroid hormones circulate in the body, large arteries are more prone to distention in the presence of increased quantities of released catecholamines, and resistance vessels are less responsive to their pressor effects due to a superimposing dilator effect. These changes might represent adaptative mechanisms in hyperthyroid states, and might depend on a greater sensitivity of endothelial beta 2-receptors to noradrenaline and adrenaline.

Animals↗
PubMed1984

Cardionatrin causes vasodilation in vitro which is not dependent on the presence of endothelial cells.

Vasodilation, in vitro, evoked by atrial extracts (cardionatrin) was compared with the relaxation due to acetylcholine and papaverine in rat precontracted aortae with and without endothelium. Ventricular extracts were tested as controls. Atrial extracts and papaverine caused a similar concentration-dependent relaxation of both preparations whereas acetylcholine failed to relax preparations without endothelium. Ventricular extracts were ineffective on both preparations. It is concluded that the response of the preparations to atrial extracts (cardionatrin) is not dependent on the presence of the endothelial cells. Some pathophysiological implications are discussed.

Acetylcholine↗
PubMed1984

Vascular reactivity in diabetes mellitus: possible role of insulin on the endothelial cell.

The response to vasoactive agents of microvessels of the rat was tested in vivo by direct microscopic observation of the exteriorized mesentery and assessment of cutaneous vascular permeability changes with Evans blue. The constrictor response to a standard amount of noradrenaline in mesenteric microvessels was fully antagonized by acetylcholine in normal, diabetic, adrenalectomized and diabetic-adrenalectomized rats. In contrast, the minimum doses of histamine or bradykinin, effective in normal or adrenalectomized animals, had to be increased about 20 fold to be active in diabetic or diabetic-adrenalectomized animals. Topical application of insulin to mesenteric microvessels of diabetic animals, in amounts not causing any increase in serum insulin levels, improved or restored the capacity of the animals to respond to histamine or bradykinin, acting as antagonists of the vasoconstrictor response to noradrenaline. Topical insulin, however, was ineffective in normal animals given 2-deoxyglucose, the acute effects of which result from cellular glucopaenia unrelated to insulin deficiency. Vascular permeability responses to intracutaneous histamine or bradykinin were decreased in animals pretreated with 2-deoxyglucose as much as in diabetic animals. Pretreatment of normal animals with indomethacin produced no effect on the responses of these animals to histamine or bradykinin, tested as antagonists of noradrenaline on mesenteric microvessels, or as vascular permeability-increasing factors in the skin. Pretreatment of normal animals with chloroquine, mepacrine or dexamethasone had no effect on the reactivity of mesenteric microvessels to histamine and bradykinin, acting as antagonists to noradrenaline. 7 It is suggested that vasoactive substances, endowed with permeability-increasing properties, evoke relaxation of microvessels through an insulin-dependent action on endothelial cells, unrelated to the release of arachidonic acid metabolites. This action would lead to increased vascular permeability, with opening of interendothelial junctions, and temporary changes in composition of extravascular fluid, which in turn, would provide the basis for vasodilatation. Diabetes mellitus apparently impairs such responses as a result of the accompanying cellular glucopaenia. Adrenal corticosteroids are not involved in the impaired responses.

Adrenalectomy↗
PubMed1983

Mechanism of action of phenylephrine on isolated guinea-pig atria rate.

1. Phenylephrine has a positive chronotropic effect on the right isolated guinea-pig atria and this effect is not modified by alpha-adrenergic blocker (phentolamine) but it is drastically inhibited by beta-adrenergic antagonists (practolol or propranolol). 2. The effect is substantially reduced by treatment with cocaine or pretreatment with reserpine. 3. Cocaine plus reserpine shift the dose-response curve for phenylephrine to the left. 4. It is concluded that positive chronotropic effect of phenylephrine has two components: direct action on beta-adrenergic receptors and an indirect action due to norepinephrine release.

Adrenergic alpha-Antagonists↗
PubMed1983

Influence of diabetes on the reactivity of mesenteric microvessels to histamine, bradykinin and acetylcholine.

1 Noradrenaline (NA) evoked a vasoconstrictor response in rat mesenteric microvessels in situ, the latency and nature of which was analogous in normal and alloxan-diabetic animals.2 Histamine and bradykinin (Bk) were capable of antagonizing the response to NA in normal but not in diabetic animals. In contrast, acetylcholine (ACh) was equally effective as an antagonist to NA in both groups of animals.3 The altered responses to histamine and Bk were not associated with hyperglycaemia since fasting rendered the diabetic animals normoglycaemic and yet did not restore the reactivity of microvessels. Previous administration of insulin to diabetic animals corrected the impaired responses to histamine and Bk.4 A similar condition of impaired responses to histamine and Bk was produced in normal animals by the intravenous injection of 2-deoxyglucose although ACh remained fully active.5 Apparently, the functional changes observed in the response to histamine or Bk, as antagonists of the vasoconstrictor reaction to NA, were not associated with a defective response of all smooth muscle. First, because ACh remained active in diabetic animals, and, second, because extravascular smooth muscles obtained from either normal or diabetic rats were equally relaxed by histamine or Bk in vitro.6 It is suggested that histamine and Bk antagonized the vasoconstrictor response of microvessels to NA through an action on lining endothelial cells resulting in increased vascular permeability and hyperosmolarity of extracellular fluids.7 The process depended on the availability of insulin, and, therefore, might be affected by intracellular glucopaenia as occurring in diabetes.8 Intracellular glucopaenia markedly affected other structures. Reduced atria rates were observed in diabetes, despite the fact that the isolated preparation responded normally to NA, ACh or tyramine. Partial substitution of glucose in the bathing fluid by 2-deoxyglucose or addition of NaF to the organ bath evoked similar changes in atria from normal animals.9 ACh which has little effect on vascular permeability must exert its vasodilator effects through mechanisms which are different from those influenced by the biochemical changes occurring in diabetes.

Acetylcholine↗
PubMed1983

Vascular reactivity in diabetes mellitus: role of the endothelial cell.

The response to vasoactive agents of microvessels in situ and large arteries in vitro was compared in normal and alloxan-diabetic rats. Noradrenaline was equally effective in evoking a constrictor response of mesenteric microvessels in normal and diabetic animals. The constrictor response to a standard amount of noradrenaline in such vessels was fully antagonized by acetylcholine or papaverine, the minimum effective doses being equivalent in normal and diabetic animals. In contrast, the minimum doses of histamine or bradykinin, effective in normal animals, had to be increased about 20 fold to be active in diabetic animals. Increased osmolarity of extracellular fluid caused a significant and equivalent increase in latency of the vasoconstrictor response of microvessels to noradrenaline in normal and diabetic animals. Concentration-effect curves, constructed from the response of isolated aortae to noradrenaline, were similar in normal and diabetic animals, provided the endothelium was removed. Diabetes only affected preparations in which the endothelium was left intact. In these, the median effective concentrations of noradrenaline were greatly increased in comparison with normal values. Precontracted aortae from normal and diabetic animals were equally relaxed by acetylcholine and histamine, provided the endothelium was left intact. Loss of the relaxant response of the preparations in all groups of animals was observed following removal of endothelial cells. It is suggested that different mechanisms may be involved in the effects of vasodilator agents on large arteries in vitro or small vessels in situ. Histamine and bradykinin which are potent permeability-increasing factors, may antagonize the vasoconstrictor response of microvessels to noradrenaline through an action on endothelial cells with increased vascular permeability and temporary changes in composition of extracellular fluid. The reactive process of endothelial cells to permeability factors was affected by diabetes mellitus. However, the response of microvessels to acetylcholine and papaverine which are devoid of permeability-increasing properties, was not influenced by diabetes.

Acetylcholine↗
PubMed1983

Stereoisomery and the release of the adrenergic neurotransmitter by indirectly acting sympathomimetics.

The isolated right rat atrium was used to investigate the chronotropic effects of dl-tranylcypromine and its d- and l-isomers. The concentration-effect curves of the three compounds were similar. The response of the preparation to the three drugs was completely blocked by pretreatment of the animal with reserpine, thus indicating an indirect effect of the drugs by the release of the natural mediator. Cocaine present in the bathing fluid partially antagonized the effect of dl-tranylcypromine and its isomers. It is concluded that the accumulation of the different forms of the drug by neural structures and the subsequent release of the neurotransmitter are not stereospecific processes. Furthermore it is suggested that the efflux of the neurotransmitter in the rat atrium may be carrier-mediated, and that this process is inhibited by cocaine.

Animals↗
PubMed1980

Anticholinesterase activity of tranylcypromine and its isomers.

The anticholinesterase (antiChE) activity of ranylcypromine (TRCY) and its isomers was studied by employing dog plasma as a cholinesterase source. Changes in arterial blood pressure, elicited by a mixture of acetylcholine (Ach) and dog plasma with or without those drugs, as an indicator of their anti ChE activity were monitored. When TRCY or one of its isomers was present in concentrations higher than 125 microM in plasma containing Ach, the hypotensive effect of the latter was preserved. Such findings provide experimental evidence that TRCY and its isomers may exert antiChE activity.

Animals↗
PubMed1979

Gastric emptying effect of d,1-tranylcypromine and its stereoisomers.

The effect of d,1-, d- and 1-tranylcypromine (Tc) on gastric emptying of rats trained to eat once a day during a 2-h period under conditions of normal or depleted catecholamine stores was studied. d,1-Tc and d-Tc reduced gastric emptying intensely and almost similarly whereas 1-Tc produced a qualitatively less intense effect. Reserpine did not modify this effect of d,1-Tc. It is concluded that d,1-Tc is the most effective form for delaying gastric emptying, this effect being mainly due to the d-isomer. Catecholamines are not involved in the gastric inhibiting effect of these drugs.

Animals↗
PubMed1979

Effects of dl-tranylcypromine on LD50 of pentobarbital in the rat.

The LD50 of pentobarbital has been determined in rats with or without pretreatment with dl-, d- or l-tranylcypromine (5 mg/kg, i.p.). The LD50 of pentobarbital was reduced to almost one half by d- or dl-tranylcypromine as compared with the l-isomer. It is concluded that dl-tranylcypromine enhances pentobarbital toxicity by inhibition of its metabolism.

Animals↗