Structure of Cerebral Arterioles in Mice Deficient in Expression of the Gene for Endothelial Nitric Oxide Synthase
We examined effects of pharmacological inhibition of nitric oxide synthase (NOS) and genetic deficiency of the endothelial isoform of NOS (eNOS) on structure and mechanics of cerebral arterioles. We measured pressure, diameter, and cross-sectional area (CSA) of the vessel wall (histologically) in maximally dilated cerebral arterioles in mice that were untreated or treated for 3 months with the NOS inhibitor, N G -nitro-L-arginine methyl ester (L-NAME; 10 mg/kg per day in drinking water).
... king water). Treatment with L-NAME increased systemic arterial mean pressure (SAP; 143Ϯ4 versus 121Ϯ4 mm Hg, PϽ0.05) and CSA (437Ϯ27 versus 310Ϯ34 m 2 , PϽ0.05). These findings suggest that hypertension induced in mice by NOS inhibition is accompanied by hypertrophy of cerebral arterioles. To determine the role of the eNOS isoform in regulation of cerebral vascular growth, we examined mice with targeted disruption of one (heterozygous) or both (homozygous) genes encoding eNOS. Wild-type littermates served as controls. SAP and CSA were significantly increased in homozygous (SAP, 141Ϯ5 versus 122Ϯ3 mm Hg in wild-type mice, PϽ0.05; CSA, 410Ϯ18 versus 306Ϯ15 m 2 in wild-type mice, PϽ0.05), but not in heterozygous (SAP, 135Ϯ4 mm Hg; CSA, 316Ϯ32 m 2 ) eNOS-deficient mice. Carotid ligation normalized cerebral arteriolar pulse pressure did not prevent increases in CSA in homozygous eNOS-deficient mice. Thus, cerebral arterioles undergo hypertrophy in homozygous eNOS-deficient mice, even in the absence of increases in arteriolar pulse pressure. These findings suggest that eNOS plays a major role in regulation of cerebral vascular growth. (Circ Res. 2004;95:822-829.) Key Words: hypertension Ⅲ L-NAME Ⅲ endothelial nitric oxide synthase deficiency Ⅲ vascular hypertrophy Original