Genetic Ablation of Caveolin‐1 does not Affect Pressure‐Induced Constriction but Alters Endothelin‐1 Pharmacology in Murine Cerebral Arteries

Abstract

Numerous phenotypic changes have been reported in mice with knockout of caveolin‐1 (KO) expression. This study evaluated cerebroarterial reactivity to investigate the role of caveolin‐1 in vascular smooth muscle function. Arterial segments were isolated from KO and wild type (WT) mice of age 6–9 months, pressure‐mounted and diameter was monitored. No difference was observed in constriction to intraluminal pressure up to 110 mmHg, further increase in pressure caused forced dilation. Constrictions to 60 mM KCl, 10 μM phenylephrine and 10 μM serotonin and dilation to 10 μM bradykinin and 16mM KCl were not different in WT and KO arteries. Concentration response curves to endothelin‐1 in WT arteries were biphasic. In KO arteries, constriction to ET1 was significantly decreased and the second low affinity phase was not observed. Decreased ET1 constriction was not restored by 100 μM L‐NAME. Myogenic tone at 70 mmHg was reversed by SKF 96365 and 2APB, known blockers of transient receptor potential (TRP) channels, in WT but only partially decreased in KO arteries. ET1 constriction was equally sensitive to SKF 96365 and 2APB in both groups. Myogenic tone was reversed by Y27632, a rho‐kinase inhibitor in both groups. Decrease in ET1 constriction by Y27632 was significantly lower in KO arteries compared to WT arteries. Constriction to pressure and ET1 may be modulated by caveolin‐1 via activation of TRP channels and rho‐kinase.