2. Academic Validation
  3. Vericiguat attenuates the dynamic gain of open-loop baroreflex function in a low-frequency range

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

  • Auton Neurosci. 2025 Oct 10:262:103354. doi: 10.1016/j.autneu.2025.103354.
Aimi Yokoi 1,  Toru Kawada 2,  Nana Hiraki 2,  Midori Kakuuchi 3,  Takuya Nishikawa 4,  Masafumi Fukumitsu 2,  Kei Sato 2,  Joe Alexander Jr 5,  Ryou Tanaka 6,  Keita Saku 7
Affiliations

Affiliations

  • 1 Tokyo University of Agriculture and Technology, Fuchu, Tokyo, 183-8509, Japan; Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka, 564-8565, Japan.
  • 2 Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka, 564-8565, Japan.
  • 3 NTTR-NCVC Bio Digital Twin Center, National Cerebral and Cardiovascular Center, Osaka, 564-8565, Japan.
  • 4 Department of Research Promotion and Management, National Cerebral and Cardiovascular Center, Osaka, 564-8565, Japan.
  • 5 Medical and Health Informatics Laboratories, NTT Research, Inc., Sunnyvale, CA, 94085, United States.
  • 6 Tokyo University of Agriculture and Technology, Fuchu, Tokyo, 183-8509, Japan.
  • 7 Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka, 564-8565, Japan; NTTR-NCVC Bio Digital Twin Center, National Cerebral and Cardiovascular Center, Osaka, 564-8565, Japan. Electronic address: saku.keita@ncvc.go.jp.
PMID: 41101266 DOI: 10.1016/j.autneu.2025.103354
Abstract

Vericiguat, a soluble Guanylate Cyclase stimulator, enhances the production of cyclic guanosine monophosphate through nitric oxide (NO)-dependent and -independent mechanisms. We examined the effects of vericiguat on the open-loop dynamic characteristics of the carotid sinus baroreflex. In anesthetized Wistar-Kyoto rats (n = 8), sympathetic nerve activity (SNA), arterial pressure (AP), and aortic flow were measured while varying carotid sinus pressure (CSP) according to a Gaussian white noise signal with a mean of 120 mmHg and a standard deviation of 20 mmHg. The neural arc transfer function from CSP to SNA, peripheral arc transfer function from SNA to AP, and total arc transfer function from CSP to AP were compared between the baseline conditions and during intravenous administrations of vericiguat (10 μg·kg-1·min-1). Vericiguat treatment reduced the asymptotic dynamic gain in the peripheral arc but not in the neural arc. It also reduced the asymptotic dynamic gain and increased the corner frequency in the total arc. These findings indicate low-frequency-dominant attenuation of dynamic gain, suggesting that vericiguat enhances the negative feedback regulation of vasoconstriction mediated by endogenous NO.

Keywords

Carotid sinus baroreflex; Rats; Sodium nitroprusside; Sympathetic nerve activity; Transfer function; Vericiguat.

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