Gene transfer of inducible nitric oxide synthase impairs relaxation in human and rabbit cerebral arteries.

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Abstract
Background and Purpose— These studies evaluated whether gene transfer of inducible nitric oxide synthase (iNOS) is a sufficient stimulus to produce vascular dysfunction in cerebral arteries. Methods— Intracranial (pial) arteries were dissected from human brain tissue obtained during elective surgery. Isolated human arteries were incubated in vitro with adenovirus containing iNOS (AdiNOS) or a nonexpressive transgene (control, AdBglII) (500 μL, 3×10 9 plaque-forming units per milliliter), and vascular function was examined 24 hours later. In anesthetized rabbits, AdiNOS or AdBglII (300 μL 1×10 10 ) was injected into the cisterna magna. Three days later, the basilar artery was removed, and reactivity was examined ex vivo. Results— In submaximally precontracted vessels, we observed impairment of NO-dependent relaxation in human cerebral arteries after gene transfer of iNOS. Maximum relaxation to bradykinin (1 μmol/L, an endothelium-dependent agonist) was 77±11% (mean±SE) after AdBglII and 31±22% ( P P Conclusions— These studies suggest that expression of iNOS may impair NO-dependent relaxation in both human and rabbit cerebral arteries.