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The ability of baroreflex activation to improve blood pressure and resistance vessel function in spontaneously hypertensive rats is dependent on stimulation parameters

Abstract

Baroreflex activation by electric stimulation of the carotid sinus (CS) effectively lowers blood pressure. However, the degree to which differences between stimulation protocols impinge on cardiovascular outcomes has not been defined. To address this, we examined the effects of short- and long-duration (SD and LD) CS stimulation on hemodynamic and vascular function in spontaneously hypertensive rats (SHRs). We fit animals with miniature electrical stimulators coupled to electrodes positioned around the left CS nerve that delivered intermittent 5/25 s ON/OFF (SD) or 20/20 s ON/OFF (LD) square pulses (1 ms, 3 V, 30 Hz) continuously applied for 48 h in conscious animals. A sham-operated control group was also studied. We measured mean arterial pressure (MAP), systolic blood pressure variability (SBPV), heart rate (HR), and heart rate variability (HRV) for 60 min before stimulation, 24 h into the protocol, and 60 min after stimulation had stopped. SD stimulation reversibly lowered MAP and HR during stimulation. LD stimulation evoked a decrease in MAP that was sustained even after stimulation was stopped. Neither SD nor LD had any effect on SBPV or HRV when recorded after stimulation, indicating no adaptation in autonomic activity. Both the contractile response to phenylephrine and the relaxation response to acetylcholine were increased in mesenteric resistance vessels isolated from LD-stimulated rats only. In conclusion, the ability of baroreflex activation to modulate hemodynamics and induce lasting vascular adaptation is critically dependent on the electrical parameters and duration of CS stimulation.

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Acknowledgements

This research was supported by Brazilian public funding from the São Paulo State Research Foundation (FAPESP). We also thank Dr. Helio Cesar Salgado for the use of his laboratory and scientific support and Dr. Daniel Penteado Martins Dias, Dr. Luiz Eduardo Virgílio Silva, and Jaci Airton Castania for expert technical assistance.

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Correspondence to Gean Domingos-Souza.

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Domingos-Souza, G., Santos-Almeida, F.M., Meschiari, C.A. et al. The ability of baroreflex activation to improve blood pressure and resistance vessel function in spontaneously hypertensive rats is dependent on stimulation parameters. Hypertens Res 44, 932–940 (2021). https://doi.org/10.1038/s41440-021-00639-9

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