Soluble Prorenin Receptor Increases Blood Pressure in High Fat–Fed Male Mice

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-associated hypertension. Therefore, in the present study, we investigated the contribution of sPRR to blood pressure elevation in the context of obesity. High-fat fed C57BL/6 male mice were infused with vehicle or sPRR (30 µg/kg/day) via subcutaneously implanted osmotic minipump for 4 weeks. Blood pressure parameters were recorded using radiotelemetry devices. Male mice infused with sPRR exhibited higher systolic blood pressure and mean arterial pressure and lower spontaneous baroreflex sensitivity than mice infused with vehicle. To define mechanisms involved in systolic blood pressure 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 systolic blood pressure. Chlorisondamine treatment exacerbated the decrease in mean arterial pressure in male mice infused with sPRR. These results demonstrated that sPRR induced autonomic nervous dysfunction. Interestingly, plasma leptin levels were increased in high-fat fed C57BL/6 male mice infused with sPRR. Overall, our results indicated that sPRR increased systolic blood pressure through an impairment of the baroreflex sensitivity and an increase in the sympathetic tone potentially mediated by leptin in high-fat fed C57BL/6 male mice.