Acute angiotensin type 1 receptor blockade restores intracranial cerebral compliance in renovascular hypertension with high sodium intake
Gabriela Maria Lucera, Jéssica Matheus Sá, Marcos Vinicius Fernandes, Rodrigo de Albuquerque Pacheco Andrade, Gustavo Frigieri, José Vanderlei Menani, Eduardo Colombari, Débora Simões Almeida ColombariBackground:
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.