Background: Angiotensin II (Ang II) induces constriction (AT(1)) and dilation (AT(2) receptors) of cerebral arterioles. High sodium intake induces changes in receptors expression and loss of AT(2)-mediated vasodilation in extracerebral vessels. We investigated whether high salt modifies the AT(2)-mediated response of cerebral arterioles.
Methods: Three-month-old male Wistar rats received drinking water supplemented or not with 1% NaCl. We measured at day 4 or 30 plasma aldosterone concentration, AT receptors expression (brain microvessels, western blot, RT-qPCR), internal diameter of pial arterioles (cranial window) following suffusion with Ang II (10(-6) mol/l, or 10(-8) mol/l + losartan 10(-5) mol/l), serotonin (5-HT, 10(-6) mol/l), sodium nitroprusside (10(-5) mol/l) and adenosine diphosphate (ADP, 10(-4) mol/l).
Results: High salt did not modify arterial pressure, baseline arteriolar diameter, vasoconstriction to Ang II or 5-HT, nor vasodilation to SNP. High salt lowered plasma aldosterone concentration (d4 138 ± 71 not significant vs. control 338 ± 73; d30 150 ± 21 P < 0.05 vs. control 517 ± 79 μmol/l). AT receptors mRNA did not change while protein level of AT(2) receptors decreased at d4 (64 ± 9% of control, P < 0.05). AT(2)-mediated vasodilation (control d4; d30 8 ± 2; 5 ± 2%) was abolished at d4 (-2 ± 2%, P < 0.05) and reversed to vasoconstriction at d30 (-7 ± 2%, P < 0.05). ADP-induced vasodilation is abolished at d30 (2 ± 2, P < 0.05 vs. control 19 ± 4%).
Conclusion: High salt specifically abolishes AT(2)-mediated vasodilation, immediately, via decreased level of AT(2) receptor protein, and after 30 days, in association with abolition of endothelial vasodilation. Such loss of AT(2)-mediated vasodilation may be deleterious in case of stroke.