Exp Physiol 94.11 pp 1103–1113 1103 Experimental Physiology – Research Paper Brainstem oxytocinergic modulation of heart rate control in rats: effects of hypertension and exercise training Keila T. Higa-Taniguchi, Jorge V. C. Felix and Lisete C. Michelini Department of Physiology & Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Brazil Oxytocinergic brainstem projections participate in the autonomic control of the circulation. We investigated the effects of hypertension and training on cardiovascular parameters after oxytocin (OT) receptor blockade within the nucleus tractus solitarii (NTS) and NTS OT and OT receptor expression. Male spontaneously hypertensive rats (SHR) and Wistar–Kyoto (WKY) rats were trained (55% of maximal exercise capacity) or kept sedentary for 3 months and chronically instrumented (NTS and arterial cannulae). Mean arterial blood pressure (MAP) and heart rate (HR) were measured at rest and during an acute bout of exercise after NTS pretreatment with vehicle or OT antagonist (20 pmol of OT antagonist (200 nl of vehicle) –1 ). Oxytocin and OT receptor were quantified ( 35 S-oligonucleotide probes, in situ hybridization) in other groups of rats. The SHR exhibited high MAP and HR (P < 0.05). Exercise training improved treadmill performance and reduced basal HR (on average -11%) in both groups, but did not change basal MAP. Blockade of NTS OT receptor increased exercise tachycardia only in trained groups, with a larger effect on trained WKY rats (+31 ± 9 versus +12 ± 3 beats min -1 in the trained SHR). Hypertension specifically reduced NTS OT receptor mRNA density (–46% versus sedentary WKY rats, P < 0.05); training did not change OT receptor density, but significantly increased OT mRNA expression (+2.5-fold in trained WKY rats and +15% in trained SHR). Concurrent hypertension- and training-induced plastic (peptide/receptor changes) and functional adjustments (HR changes) of oxytocinergic control support both the elevated basal HR in the SHR group and the slowing of the heart rate (rest and exercise) observed in trained WKY rats and SHR. (Received 12 June 2009; accepted after revision 20 July 2009; first published online 28 July 2009) Corresponding author L. C. Michelini: Department of Physiology & Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1524, 05508-900 Sao Paulo, SP, Brazil. Email: michelin@usp.br Accumulated experimental evidence has shown that exercise training promotes several beneficial adjustments in the circulatory system of hypertensive individuals, such as remodelling of the heart with simultaneous stroke volume increase and heart rate decrease (Clausen, 1977; Scheuer & Tipton, 1977; American College of Sports Medicine, 2004), reversal of hypertrophic remodelling of hypertensive arterioles in exercised muscles (Amaral et al. 2000; Melo et al. 2003) accompanied by capillary angiogenesis and small venule neoformation (Hudlicka et al. 1992; Amaral et al. 2000, 2001; Melo et al. 2003; Prior et al. 2004) and predominance of relaxing over contracting endothelial factors (Laughlin, 1995), resulting in decreased resistance and increased vascular conductance in exercised tissues. Exercise training has also been recognized as an important therapeutic tool to change autonomic circulatory control. It improves vagal outflow and decreases peripheral sympathetic activity (Clausen, 1977; Smith et al. 1989; Negrao et al. 1992a, 1993; Collins et al. 2000; Mueller, 2007), causing both resting bradycardia and smaller exercise tachycardia (characteristic markers of training) besides contributing to the reduction of the vascular resistance. Our knowledge of the central mechanisms conferring potential benefits of exercise training on autonomic control is, however, limited (see reviews by Waldrop et al. 1996; Potts, 2006; Raven et al. 2006; Michelini, 2007a,b). We and others have shown that oxytocinergic (OTergic) projections from pre-autonomic neurons of the paraventricular nucleus of the hypothalamus (PVN) to the nucleus tractus solitarii (NTS) and other bulbar areas are involved in both reflex control of the heart and adjustments of the heart rate (HR) during dynamic exercise. Within the solitary–vagal complex (NTS + dorsal C  2009 The Authors. Journal compilation C  2009 The Physiological Society DOI: 10.1113/expphysiol.2009.049262