Participation of autonomic nervous system in the pathogenesis of Chagas disease.

Evidences accumulated over the last decade give adequate proof for the existence of circulating antibodies in Chagas disease which binds to beta adrenergic and muscarinic cholinergic receptor of lymphocytes and myocardium. The interaction of the antibodies with lymphocytes and cardiac neurotransmitter receptors behaving as an agonist, triggers in the cells intracellular signal transductions that alter the physiological behaviour of this cells. These events converted the cells in pathologically active cells. Thus, antibodies activating beta adrenergic receptors of T helper (Th) lymphocytes increase cAMP and releases PGE2 by T suppressor/cytotoxic (Ts/c) cell, inducing in this way, immunosuppression by simultaneous inhibition of Th and stimulation of Ts/c cell function. All these antibodies actions were mimetized by parasite's membranes. On the other hand, the interaction of antibodies against heart beta adrenergic and cholinergic receptors trigger physiologic, morphologic, enzymatic and molecular alterations, that leading to cardiac damage. The analysis of the prevalence and distribution of these antibodies shows a strong association with seropositive asymptomatic patients with autonomic dysfunction in comparison with those asymptomatic without alteration of the heart autonomic disorders; pointing to that the presence of these antibodies may partially explain the cardiomyoneuropathy of Chagas disease, in which the sympathetic and parasympathetic systems are affected. The deposit of autoantibodies on the myocardial neurotransmitter receptors, behaving like an agonist, could induced desensitization and/or down regulation of the receptors. This in turn, could led to a progressive blockade of myocardium neurotransmitter receptors, with sympathetic and parasympathetic dennervation, a phenomenon that has been described in the course of Chagas cardioneuropathy.

Participation of autonomic nervous system in the pathogenesis of Chagas disease.

Evidences accumulated over the last decade give adequate proof for the existence of circulating antibodies in Chagas disease which binds to beta adrenergic and muscarinic cholinergic receptor of lymphocytes and myocardium. The interaction of the antibodies with lymphocytes and cardiac neurotransmitter receptors behaving as an agonist, triggers in the cells intracellular signal transductions that alter the physiological behaviour of this cells. These events converted the cells in pathologically active cells. Thus, antibodies activating beta adrenergic receptors of T helper (Th) lymphocytes increase cAMP and releases PGE2 by T suppressor/cytotoxic (Ts/c) cell, inducing in this way, immunosuppression by simultaneous inhibition of Th and stimulation of Ts/c cell function. All these antibodies actions were mimetized by parasites membranes. On the other hand, the interaction of antibodies against heart beta adrenergic and cholinergic receptors trigger physiologic, morphologic, enzymatic and molecular alterations, that leading to cardiac damage. The analysis of the prevalence and distribution of these antibodies shows a strong association with seropositive asymptomatic patients with autonomic dysfunction in comparison with those asymptomatic without alteration of the heart autonomic disorders; pointing to that the presence of these antibodies may partially explain the cardiomyoneuropathy of Chagas disease, in which the sympathetic and parasympathetic systems are affected. The deposit of autoantibodies on the myocardial neurotransmitter receptors, behaving like an agonist, could induced desensitization and/or down regulation of the receptors. This in turn, could led to a progressive blockade of myocardium neurotransmitter receptors, with sympathetic and parasympathetic dennervation, a phenomenon that has been described in the course of Chagas cardioneuropathy.

Trypanosoma cruzi attachment to lymphocyte muscarinic cholinergic and beta adrenergic receptors modulates intracellular signal transduction.

Plasma membrane vesicles of Trypanosoma cruzi (PMVs) formed saturation binding isotherms with naive murine T lymphocytes. Parasite membrane attachment to the muscarinic cholinergic receptors of Lyt 2.2+T cells (suppressor cells) resulted in the synthesis of cGMP, attenuation of cAMP levels and in the secretion of prostaglandin E2, an immunoregulator effector substance. These T suppressor cell signals were blunted by atropine and by monospecific antibody against T. cruzi surface epitopes. The interaction of T. cruzi PMVs with the beta adrenergic receptors of Lyt L3T4+T cells (helper cells) resulted in the synthesis of cAMP and in the attenuation of cGMP levels. T helper cells did not secrete prostaglandin E2 when T. cruzi PMVs were added to this system. These T helper cell signals were blunted by propranolol and by monospecific antibody against T. cruzi surface epitopes. The interaction of T. cruzi with T lymphocytes may result, therefore, in the down-regulation of the immune response induced by prostaglandin E2 T suppressor cell secretion and by cAMP inhibition of proliferation of T helper cells.

Prostacyclin, its fatty acid precursor and its metabolites on the inotropic function of and on the prostanoid generation by diabetic arteries.

Relationships between arachidonic acid (AA) metabolism and contractile responses to Na arachidonate (NaA) to prostacyclin (PGI2) and to some of its metabolites, in mesenteric arteries, isolated from sham operated and from diabetic, totally pancreatectomized dogs; were studied. Arachidonate and prostacyclin enhanced the resting basal tone of preparations from pancreatectomized animals but depressed it in vessels from intact normal controls or from sham operated dogs. Inhibitors of thromboxane A2 (TXA2) biosynthesis, abolished in vitro the vasoconstring effect of NaA and PGI2 in diabetics; whereas inhibitors of PGI2 biosynthesis blocked the vasodilating influence of NaA in normal mesenterics. Additionally, antagonists of cyclooxygenase activity precluded both, the vasoconstricting and vasodilating actions of NaA in normal and in diabetic arteries, respectively, as well as the PGI2 tone enhancement in vessels from diabetics. Blockers of adrenoreceptors and antagonists of lipoxygenases, failed to block the positive inotropic effects of PGI2 in mesenterics from diabetic dogs. On the other hand, 6-keto-PGF1 alpha did not evoke contractile influences, either in diabetics or in controls, whereas 6-keto-PGE1 induced, in both groups, a dose-dependent relaxation. In arteries from pancreatectomized animals treated with insulin, PGI2 induced a biphasic effect (constriction and relaxation) of magnitudes between those seen in normal controls or sham operated and, in untreated diabetics. The basal radioconversion of exogenous [1-14C]-AA, evidenced that mesenterics from diabetic animals generated more TXB2 than vessels from intact normal control or from sham-operated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)