Sex-dependent Changes in Intracranial Pressure and Intracranial Compliance in a Rat Model of Renovascular Hypertension

Intracranial pressure (ICP) reflects the pressure within the cranium, while intracranial compliance (ICC) indicates the brain's capacity to accommodate changes in intracranial volume without substantial increases in ICP. ICC serves as a critical marker for understanding the brain's adaptive mechanisms, particularly in pathological conditions such as hypertension. This study evaluated ICC during a 10-minute artificial cerebrospinal fluid (aCSF) infusion to incrementally increase ICP in male and female two-kidney, one-clip (2K1C) renovascular hypertensive rats. Male and female Holtzman rats (180–210 g) underwent either sham surgery (normotensive, NT) or partial left renal artery occlusion to induce 2K1C hypertension. Six weeks post-surgery, rats were anesthetized with urethane (1.4 g/kg i.v.), tracheostomized, and artificially ventilated. Arterial blood pressure was recorded via femoral artery catheterization, and ICP was monitored using a sensor in the lateral ventricle, where aCSF was infused (100 µL over 10 minutes at 10 µL/min). ICC was calculated as the change in volume (ΔV) per unit change in pressure (ΔP). Baseline mean arterial pressure (MAP) was significantly higher in 2K1C rats compared to their NT counterparts (Male: 149 ± 10 vs. 96 ± 14 mmHg; Female: 147 ± 15 vs. 87 ± 11 mmHg, p < 0.05). Male 2K1C rats exhibited elevated baseline ICP compared to NT (8.5 ± 3.1 vs. 4.3 ± 1.2 mmHg, p < 0.05), while no significant baseline ICP differences were observed between female 2K1C and NT rats (7.9 ± 4.2 vs. 6.4 ± 2.9 mmHg, p > 0.05). During aCSF infusion, ICP increases were more pronounced in hypertensive rats (Male: 26.1 ± 7.3 vs. 15.7 ± 3.4 mmHg; Female: 19.5 ± 7.4 vs. 14.1 ± 1.8 mmHg at 10 minutes, p < 0.05). ICC was significantly reduced in 2K1C rats relative to NT controls (Male: 5.9 ± 1.2 vs. 9.3 ± 2.4 µL/mmHg; Female: 9.0 ± 2.4 vs. 13.2 ± 2.9 µL/mmHg, p < 0.05). Furthermore, male 2K1C rats exhibited lower ICC than female 2K1C rats (5.9 ± 1.2 vs. 9.0 ± 2.4 µL/mmHg, p < 0.05). These findings indicate that renovascular hypertension impairs ICC in both sexes, with a more pronounced effect in males. This highlights both the pathological impact of hypertension on brain compliance and sex-specific variability in its severity. Funding: FAPESP, CAPES PRINT (88887.194785/2018-00), CNPq and Brain4Care. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.