Rats underwent two surgical procedures at 10 day intervals. To test this hypothesis, we used genetic tools, a microinjection of adenoviral vectors (Ads) carrying the tagged gene for the OT receptor into the PVN, to induce an overexpression of OT receptors, and pharmacological tools, microinjections of a selective OT receptor antagonist into the PVN of conscious transfected and non-transfected wild-type (Wt)rats, both during baseline and stressful conditions. We hypothesized that, by increasing the number of OT receptors in the PVN and by selectively blocking their activity, we can modulate PVN neuronal activity involved in autonomic cardiovascular control. The focus of the present work is the role of OT receptors found in the PVN, which have been reported to play an important role in autoregulation of magnocellular neuronal activity (Richard et al., 1997). OT receptors belong to the GPCR family coupled to PLC signalling pathways (see Alexander et al., 2013), and are widely distributed in the periphery and CNS (Freund-Mercier et al., 1987 Gimpl and Fahrenholz, 2001). ![]() OT produces its effects by the stimulation of a specific OT receptor, well defined in terms of genes, protein structure and pharmacology (Rozen et al., 1995 Manning et al., 2012). A reduction in OT mRNA in the PVN and OT receptor mRNA in the brainstem has been demonstrated in genetically hypertensive rats (Martins et al., 2005), while a decline in central OT was associated with increased cardiovascular reactivity to stress in rats surviving myocardial infarction (Wsol et al., 2009). In vivo animal studies indicate that OT mediates the HR response to exercise (Martins et al., 2005) and HR adjustment to stress (Wsol et al., 2008). OT neurons located in the parvocellular part of the PVN project to the brainstem vagal nuclear complex (nucleus of the solitary tract – NTS, nucleus ambiguus – NAm and dorsal nucleus of vagus – DVN), rostroventrolateral medulla (RVLM) and the intermediolateral column of the spinal cord (IML) where OT influences parasympathetic and sympathetic outflow to the heart and the blood vessels (Sawchenko and Swanson, 1982 Lang et al., 1983 Zerihun and Harris, 1983 Hosoya et al., 1995 Jansen et al., 1995 Hallbeck et al., 2001 Geerling et al., 2010). In addition to its peripheral action, OT exerts endocrine and neuromodulator effects on the circulation (Haanwinckel et al., 1995 Randolph et al., 1998). OT has been shown to exert direct negative inotropic and chronotropic effects on the heart (Costa-e-Sousa et al., 2005), to produce weak vasoconstriction (Suzuki et al., 1992) and NO-dependent vasodilatation (Katusic et al., 1986). ![]() Peripherally, an independent OT system has been discovered in the heart and the blood vessels, and is associated with heart development, heart renewal and natriuresis (Gutkowska and Jankowski, 2012 Japundzic-Zigon, 2013). In addition to its well established roles in reproduction and maternity, convincing evidence has accumulated in the past few decades to suggest that oxytocin (OT), a peptide hormone mainly synthesized in the hypothalamic paraventricular (PVN) and supraoptic nuclei, is also involved in the control of the circulation.
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