Abstract P1104: The Infusion of the Soluble Prorenin Receptor Increases Blood Pressure in High-Fat Fed Male Mice

Abstract

Obesity-related hypertension is a major public health concern. We recently demonstrated that plasma levels of the soluble form of the prorenin receptor (sPRR) were elevated in obesity. In the present study, we aimed to determine whether sPRR contributed to blood pressure (BP) elevation in the context of obesity. High-fat fed C57BL/6 male mice were infused with vehicle (Veh) or sPRR (sPRR, 30 μg/kg) via subcutaneously implanted osmotic minipump for 4 weeks. BP parameters were recorded using radiotelemetry devices (n=6/groups). Male mice infused with sPRR exhibited higher systolic blood pressure (SBP. Veh: 133±1 mmHg, sPRR: 141±2 mmHg, P<0.05) and mean arterial pressure (MAP. Veh: 116±1 mmHg, sPRR: 124±2 mmHg, P<0.05) and lower spontaneous baroreflex sensitivity (Veh: 3.8±1.2 ms/ mmHg, sPRR: 2.1±0.5 ms/ mmHg, P<0.05) than mice infused with vehicle. To define mechanisms involved in BP elevation, mice were injected with an angiotensin-II type 1 receptor antagonist (losartan), a muscarinic receptor antagonist (atropine), a β-adrenergic antagonist (propranolol) and a ganglionic blocker (chlorisondamine). Losartan did not blunt sPRR-induced elevation in SBP. However, SBP response to angiotensin II was increased in mice infused with sPRR suggesting that AngII could potentiate sPRR-induced elevation in SBP. Chlorisondamine treatment exacerbated the decrease in mean arterial pressure in male mice infused with sPRR compared with vehicle (MAP. Veh: -21±1 mmHg, sPRR: -29±1 mmHg, P<0.05). Overall, we demonstrated that sPRR increased SBP through an impairment of the baroreflex sensitivity and an increase in the sympathetic tone in high-fat fed C57BL/6 male mice.