APLN and hypertensive disorder: While studies support apelin acting peripherally as an anti-hypertension factor (Zhong et al., 2005; Sonmez et al., 2010; Chandra et al., 2011; Zhu et al., 2013), neurological pathways profoundly influence peripheral homeostatic systems, and centrally administered [Pyr1]apelin-13 [the predominant apelin isoform in the cardiovascular system (Maguire et al., 2009)] has been shown to increase mean arterial blood pressure (MABP) in normotensive rats (Seyedabadi et al., 2002; Kagiyama et al., 2005; Zhang et al., 2009; Griffiths et al., 2017).