Vericiguat attenuates the dynamic gain of open-loop baroreflex function in a low-frequency range

Area of Science:

• Cardiovascular Physiology
• Pharmacology
• Neuroscience

Background:

• Vericiguat is a soluble guanylate cyclase stimulator that increases cyclic guanosine monophosphate levels.
• Nitric oxide (NO) plays a crucial role in regulating vascular tone and blood pressure.
• The carotid sinus baroreflex is a key mechanism for short-term blood pressure control.

Purpose of the Study:

• To investigate the effects of vericiguat on the dynamic characteristics of the carotid sinus baroreflex.
• To determine how vericiguat influences the neural and peripheral arcs of the baroreflex.
• To elucidate the role of vericiguat in modulating sympathetic nerve activity and arterial pressure regulation.

Main Methods:

• Anesthetized Wistar-Kyoto rats (n=8) were used to assess baroreflex dynamics.
• Carotid sinus pressure (CSP) was varied using a Gaussian white noise signal.
• Sympathetic nerve activity (SNA), arterial pressure (AP), and aortic flow were continuously monitored.
• Transfer function analysis was employed to compare baroreflex arcs before and during vericiguat administration.

Main Results:

• Vericiguat administration reduced the asymptotic dynamic gain in the peripheral baroreflex arc (SNA to AP).
• The neural arc (CSP to SNA) dynamic gain was not significantly altered by vericiguat.
• Vericiguat decreased the total arc (CSP to AP) asymptotic dynamic gain and increased its corner frequency.

Conclusions:

• Vericiguat attenuates the dynamic gain of the baroreflex, particularly at lower frequencies, indicating enhanced feedback regulation.
• The findings suggest that vericiguat improves the negative feedback control of vasoconstriction mediated by endogenous nitric oxide.
• Vericiguat's effects on baroreflex dynamics may contribute to its therapeutic benefits in cardiovascular conditions.