Central mechanisms involved in pilocarpine-induced pressor response

Abstract

Pilocarpine (cholinergic muscarinic agonist) injected peripherally may act centrally to produce pressor responses; in the present study, using c-fos immunoreactive expression, we investigated the forebrain and brainstem areas activated by pressor doses of intravenous (i.v.) pilocarpine. In addition, the importance of vasopressin secretion and/or sympathetic activation and the effects of lesions in the anteroventral third ventricle (AV3V) region in awake rats were also investigated. In male Holtzman rats, pilocarpine (0.04 to 4μmol/kg b.w.) i.v. induced transitory hypotension followed by long lasting hypertension. Sympathetic blockade with prazosin (1mg/kg b.w.) i.v. or AV3V lesions (1 day) almost abolished the pressor response to i.v. pilocarpine (2μmol/kg b.w.), whereas the vasopressin antagonist (10μg/kg b.w.) i.v. reduced the response to pilocarpine. Pilocarpine (2 and 4μmol/kg b.w.) i.v. increased the number of c-fos immunoreactive cells in the subfornical organ, paraventricular and supraoptic nuclei of the hypothalamus, organ vasculosum of the lamina terminalis, median preoptic nucleus, nucleus of the solitary tract and caudal and rostral ventrolateral medulla. These data suggest that i.v. pilocarpine activates specific forebrain and brainstem mechanisms increasing sympathetic activity and vasopressin secretion to induce pressor response.

Sodium intake combining cholinergic activation and noradrenaline into the lateral parabrachial nucleus

“…Inhibitory signals for sodium and water intake arise from arterial baroreceptors or cardiopulmonary receptors that are activated by increases in arterial pressure or body fluid volume (Johnson and Thunhorst, 1997;De Gobbi et al, 2008). Therefore, a reason for the absence of hypertonic NaCl intake in rats treated with central cholinergic agonists might be the inhibitory signals produced in response to the increases in arterial pressure caused by these treatments (Trendelenburg, 1961;Hoffman et al, 1977;Imai et al, 1989;Thunhorst and Johnson, 1994;Johnson and Thunhorst, 1997;Takakura et al, 2003Takakura et al, , 2005Takakura et al, , 2011Borella et al, 2008). Reducing the action of the inhibitory signals with bilateral injections of methysergide (serotonergic receptor antagonist) into the LPBN results in significant ingestion of hypertonic NaCl in rats treated with the cholinergic agonist carbachol intracerebroventricularly (i.c.v.)…”

Functional Neuroplasticity in the Nucleus Tractus Solitarius and Increased Risk of Sudden Death in Mice with Acquired Temporal Lobe Epilepsy

“…Peri-ictal, centrally originating or peripheral autonomic irregularities leading to cardiorespiratory collapse may be the immediate cause of death in SUDEP ( Ryvlin et al, 2013 ), but few studies have been aimed at identifying mechanisms underlying this autonomic failure. Seizures can increase activity of neurons in brainstem autonomic areas, independently of physical activity or peripheral metabolic influences ( Kanter et al, 1995 ; Takakura et al, 2011 ), and autonomic irregularities often develop over time in individuals with epilepsy, implicating central or peripheral autonomic reactive neuroplasticity as a potential driver of increased SUDEP risk in patients and in rodent epilepsy models ( Glasscock et al, 2010 ; Massey et al, 2014 ; Biet et al, 2015 ). Thus, recurrent seizures might induce changes in central or systemic physiologic functions that increase the risk for sudden death.…”