Introduction: There is significant evidence for the existence of intracranial baroreceptor mechanism(s) capable of sensing physiological changes in cerebral blood flow (Marina et al., 2020). However, little is known about the sensitivity of intracranial baroreceptors to changes in brain perfusion and their interaction with inputs from the peripheral baroreceptors. The aim of this study was to characterise the cardiovascular (heart rate and systemic arterial blood pressure, ABP) responses to small changes in cerebral perfusion pressure induced by experimental manipulation of intracranial pressure (ICP).

Methods: The experiments were performed in accordance with the UK Animals (Scientific Procedures) Act (1986). Adult Sprague-Dawley rats (250–300 g) were anesthetized with urethane (induction: 1.3 g kg−1, i.p.; maintenance: 10–25 mg kg−1 h−1, i.v.). The femoral artery and vein were cannulated for measurement of ABP and administration of anaesthetic. The trachea was cannulated, and the animal was mechanically ventilated with room air. The left lateral cerebral ventricle was cannulated and connected via a saline-filled mini-catheter to a pressure transducer to record ICP. The right lateral cerebral ventricle was cannulated and connected via a saline-filled mini-catheter to a “water column” to allow controlled manipulation of ICP.

Results: The resting ICP in rats anesthetized with urethane was 6.2 ± 0.7 mmHg (n=8). Following a small craniotomy that reduced ICP to 0, ABP decreased by 21.1 ± 6.0 mmHg (p=0.033; n=6) within 30 minutes of intracranial decompression. Restoring the integrity of the intracranial space increased ABP by 9.1 ± 3.1 mmHg). Increasing ICP by 5, 10, 15 and 20 mmHg (n=8) triggered stereotypical compensatory increases in ABP and heat rate. In response to a 5 mmHg increase in ICP, ABP increased by 18.1 ± 4.1 mmHg (p=0.01) and heart rate increased by 25 ± 11 BPM (p=0.16). In response to a 10 mmHg increase in ICP, ABP increased by 30.0 ± 5.6 mmHg (p=0.003) and heart rate increased by 47 ± 15 BPM (p=0.046). In response to a 15 mmHg increase in ICP, ABP increased by 42.4 ± 6.4 mmHg (p<0.001) and heart rate increased by 70 ± 17 BPM, p=0.016). In response to a 20 mmHg increase in ICP, ABP increased by 49.6 ± 8.3 mmHg (p=0.002) and heart rate increased by 92 ± 17 BPM (p=0.0031). In conditions of complete denervation of arterial baroceptors (bilateral sino-aortic denervation), ABP responses triggered by increases in ICP were greatly exaggerated.

Conclusion: These data indicate that intracranial baroceptor mechanism is highly sensitive to changes in cerebral perfusion within the physiological range and suggest that cerebral perfusion pressure is an important determinant of systemic ABP. The data also suggest that activation of intracranial baroreceptor mechanism effectively overrides the inputs from the peripheral baroreceptors.