Acute effects of vericiguat on urine excretion during baroreflex-mediated sympathetic arterial pressure regulation in male rats

Vericiguat is a soluble Guanylate Cyclase stimulator that acts via both nitric oxide-dependent and -independent mechanisms. Previously, we found that vericiguat decreases arterial pressure (AP) primarily by reducing systemic vascular resistance without significantly affecting sympathetic nerve activity. In this study, we investigated whether the AP reduction by vericiguat decreases urine excretion. In male Wistar-Kyoto rats (n = 8), the bilateral carotid sinus baroreceptor regions were isolated from the systemic circulation. The relationship between AP and urine excretion was examined during baroreflex-mediated AP changes before and during intravenous vericiguat administration (10 μg·kg^-1·min^-1). Vericiguat significantly decreased the operating point AP (104.6 ± 4.2 vs. 85.0 ± 4.1 mmHg, P = 0.008), primarily by decreasing the slope of the baroreflex peripheral arc. However, it maintained urine excretion at the operating point AP (55.5 ± 5.9 vs. 59.8 ± 6.9 μL·min^-1·kg^-1, P = 0.250) by significantly increasing the slope of the relationship between AP and normalized urine flow (0.53 ± 0.09 vs. 0.99 ± 0.14 μL·min^-1·kg^-1·mmHg^-1, P = 0.008). The maintenance of urine excretion during vericiguat administration might be beneficial for patients with fluid retention.

Baroreflex equilibrium diagram; Open-loop analysis; Pressure diuresis; Renal blood flow; Soluble guanylate cyclase.