Vasopressin V 1 a receptors mediate the hypertensive effects of [ Pyr 1 ] apelin-13 in the rat rostral ventrolateral medulla

Apelin is a ubiquitous peptide that can elevate arterial blood pressure (ABP) yet understanding of the mechanisms involved remain incomplete. Bilateral microinjection of [Pyr1]apelin-13 into the rostral ventrolateral medulla (RVLM), a major source of sympathoexcitatory neurones, increases ABP and sympathetic nerve activity. We aimed to investigate the potential involvement of neurotransmitter systems through which the apelin pressor response may occur within the RVLM. Adult male Wistar rats were anaesthetized and ABP was monitored via a femoral arterial catheter. Bilateral RVLM microinjection of [Pyr1]apelin-13 significantly increased ABP (9 ± 1 mmHg) compared to saline (−1 ± 2mmHg; P < 0.001), which was blocked by pretreatment with the apelin receptor antagonist, F13A (0 ± 1 mmHg; P < 0.01). The rise in ABP was associated with an increase in the low frequency spectra of systolic BP (13.9 ± 4.3% total power; P < 0.001), indicative of sympathetic vasomotor activation. The [Pyr1]apelin-13-mediated pressor response and the increased low frequency spectra of systolic BP response were fully maintained despite RVLM pretreatment with the angiotensin II type 1 receptor antagonist losartan, the oxytocin receptor antagonist desGly-NH2, d(CH2)5[D-Tyr,Thr]OVT, the ionotropic glutamate receptor antagonist kynurenate or the GABAA antagonist bicuculline (P > 0.05). By contrast, the [Pyr1]apelin-13 induced pressor and sympathoexcitatory effects were abolished by pretreatment of the RVLM with the vasopressin V1a receptor antagonist, SR 49059 (−1 ± 1 mmHg; 1.1 ± 1.1% total power, respectively; P < 0.001). These findings suggest that the pressor action of [Pyr1]apelin-13 in the RVLM of normotensive rats is not mediated via angiotensin II type 1 receptor, oxytocin, ionotropic glutamate or GABAA receptors but instead involves a close relationship with the neuropeptide modulator vasopressin. C © 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society DOI: 10.1113/JP274178 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. 2 P. R. Griffiths and others J Physiol 000.00 (Resubmitted 13 February 2017; accepted after revision 27 February 2017; first published online 2 March 2017) Corresponding author A. -M. O’Carroll: Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, University of Bristol, Whitson Street, Bristol BS1 3NY, UK. Email: a.m.ocarroll@bristol.ac. uk Abbreviations Ang II, angiotensin II; APJ, apelin receptor; BP, blood pressure; HR, heart rate; HRV, heart rate variability; MABP, mean arterial blood pressure; NTS, nucleus tractus solitarius; OT, oxytocin; dOVT, desGly-NH2, d(CH2)5[D-Tyr,Thr]OVT; PVN, parvocellular paraventricular nucleus; RVLM, rostral ventrolateral medulla; SBPV, systolic blood pressure variability; SHR, spontaneously hypertensive rats; SNA, sympathetic nerve activity; SON, supraoptic nucleus; VP, vasopressin; WKY, Wistar Kyoto.