Key result
Acute i.v. losartan (10 mg/kg) improved intracranial cerebral compliance in 2K1C rats consuming 0.3 M NaCl despite no significant reduction in MAP or ICP.
Why the study?
Central losartan fails to alter blood pressure in renovascular hypertensive (2K1C) rats that voluntarily consume hypertonic saline. Whether systemic intravenous losartan would reduce blood pressure and affect intracranial pressure and cerebral compliance in 2K1C rats given ad libitum access to 0.3 M NaCl was unknown.
Does acute intravenous losartan reduce blood pressure and intracranial pressure and improve intracranial cerebral compliance in renovascular hypertensive rats with high sodium intake?
Does acute intravenous losartan reduce blood pressure and intracranial pressure and improve intracranial cerebral compliance in renovascular hypertensive rats with high sodium intake?
In a rat model of renovascular hypertension with high sodium intake, acute intravenous losartan restores intracranial cerebral compliance independently of blood pressure and intracranial pressure reductions.
Improves cerebral compliance independently of MAP/ICP in this renovascular model; leaves open translation to human hypertension.
BACKGROUND: Acute intravenous (i.v.) losartan, an angiotensin type 1 receptor (AT1R) antagonist, normalizes elevated mean arterial pressure (MAP) and intracranial pressure (ICP) and improves brain compliance in renovascular hypertensive rats (two-kidney, one-clip; 2K1C). However, central losartan fails to alter blood pressure in 2K1C rats that voluntarily consume hypertonic saline, a normally aversive solution. We therefore tested whether systemic losartan also would reduce blood pressure (BP) in 2K1C rats given ad libitum access to 0.3 M NaCl (2K1C_Na) and examined its effects on ICP and intracranial cerebral compliance (ICC). METHODS: Male Holtzman rats underwent left renal artery clipping to induce renovascular hypertension. Cardiovascular parameters were recorded in awake or anaesthetized animals, and water and sodium intake, serum (SNa), and cerebrospinal fluid (CSFNa) sodium concentrations were measured. RESULTS: Hypertensive rats exhibited greater water intake than SHAM_Na, and 2K1C_Na rats consumed large amounts of 0.3 M NaCl. Although SNa and CSFNa did not differ among groups, CSFNa was higher than SNa in 2K1C_Na rats. Intravenous losartan (10 mg/kg of body weight) significantly reduced MAP and ICP in 2K1C rats but not in 2K1C_Na animals. Following hexamethonium (30 mg/kg of body weight), MAP and ICP decreased in both 2K1C_Na and SHAM_Na rats. Notably, losartan improved brain compliance in 2K1C_Na rats despite no significant changes in MAP or ICP. CONCLUSIONS: These findings indicate that acute AT1R blockade enhances ICC independently of unchanged MAP in renovascular hypertension with high sodium intake, suggesting a potential neuroprotective role of losartan regardless of ICP and MAP levels.
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Lucera et al. (2026) studied Renovascular hypertension (two-kidney, one-clip; 2K1C) with high sodium intake. Intravenous losartan (and hexamethonium) vs. Sham-operated rats and 2K1C rats without 0.3 M NaCl access was evaluated on Mean arterial pressure (MAP), intracranial pressure (ICP), and intracranial cerebral compliance (ICC). Acute i.v. losartan (10 mg/kg) improved intracranial cerebral compliance in 2K1C rats consuming 0.3 M NaCl despite no significant reduction in MAP or ICP.
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