Suppressed baroreflex peripheral arc overwhelms augmented neural arc and incapacitates baroreflex function in rats with pulmonary arterial hypertension

Abstract

New Findings What is the central question of this study?The impact of pulmonary arterial hypertension on open‐loop baroreflex function, which determines how powerfully and rapidly the baroreflex operates to regulate arterial pressure, remains poorly understood. What is the main finding and its importance?The gain of the baroreflex total arc, indicating the baroreflex pressure‐stabilizing function, is markedly attenuated in rats with monocrotaline‐induced pulmonary arterial hypertension. This is caused by a rightward shift of the baroreflex neural arc and a downward shift of the peripheral arc. These findings contribute greatly to our understanding of arterial pressure regulation by the sympathetic nervous system in pulmonary arterial hypertension. Abstract Sympathoexcitation has been documented in patients with established pulmonary arterial hypertension (PAH). Although the arterial baroreflex is the main negative feedback regulator of sympathetic nerve activity (SNA), the way in which PAH impacts baroreflex function remains poorly understood. In this study, we conducted baroreflex open‐loop analysis in a rat model of PAH. Sprague–Dawley rats were injected with monocrotaline (MCT) s.c. to induce PAH (60 mg kg−1; n = 11) or saline as a control group (CTL; n = 8). At 3.5 weeks after MCT injection, bilateral carotid sinuses were isolated, and intrasinus pressure (CSP) was controlled while SNA at the coeliac ganglia and arterial pressure (AP) were recorded. To examine the static baroreflex function, CSP was increased stepwise while steady‐state AP (total arc) and SNA (neural arc) responses to CSP and the AP response to SNA (peripheral arc) were measured. Monocrotaline significantly decreased the static gain of the baroreflex total arc at the operating AP compared with CTL (−0.80 ± 0.31 versus −0.22 ± 0.22, P < 0.05). Given that MCT markedly increased plasma noradrenaline, an index of SNA, by approximately 3.6‐fold compared with CTL, calibrating SNA by plasma noradrenaline revealed that MCT shifted the neural arc to a higher SNA level and shifted the peripheral arc downwards. Monocrotaline also decreased the dynamic gain of the baroreflex total arc (−0.79 ± 0.16 versus −0.35 ± 0.17, P < 0.05), while the corner frequencies that reflect the speed of the baroreflex remained unchanged (0.06 ± 0.02 versus 0.08 ± 0.02 Hz, n.s.). In rats with MCT‐induced PAH, the suppressed baroreflex peripheral arc overwhelms the augmented neural arc and, in turn, attenuates the gain of the total arc, which determines the pressure‐stabilizing capacity of the baroreflex.

Vagal nerve stimulation preserves right ventricular function in a rat model of right ventricular pressure overload

“…Thus, left‐sided ventricular hypertrophy induces parasympathetic deactivation. We previously reported decreases in LF and HF components of HRV in both monocrotaline‐induced PH 18 and Sugen/hypoxia PH models. 14 Our present results are consistent with previous reports and indicate that RVH caused by PAB also induces autonomic imbalance.…”

“… 14 We have repeatedly reported on the method for deriving stable HRV in freely moving rats. 14 , 18 We used power spectral density (PSD; ms 2 /Hz) to quantify the HRV. Beat‐to‐beat (RR) intervals were obtained from 10‐min telemetric ECG recordings during the daytime.…”

“…We evaluated heart rate variability (HRV) under the conscious state at 2 weeks after initiation of VNS (Week 4) using an ECG telemetry system (TA11ETA‐F10 Implant; Data Science International) 14 . We have repeatedly reported on the method for deriving stable HRV in freely moving rats 14,18 . We used power spectral density (PSD; ms 2 /Hz) to quantify the HRV.…”