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1 Departments of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA
* To whom correspondence should be addressed. E-mail: ggeary{at}som.llu.edu.
The lower limits of cerebral blood flow autoregulation shifts toward high pressures in aged compared to young rats. Intraluminal pressure stimulates contractile mechanisms in cerebral arteries that might, in part, cause an age-dependent shift in autoregulation. The current project tested two hypotheses. First, cerebral artery tone is greater in isolated arteries from aged compared to mature adult rats. Second, aging decreases the modulatory effect of endothelium-derived nitric oxide and increases vascular smooth muscle Ca2+ sensitivity. Isolated segments of middle cerebral arteries from male 6, 12, 20, and 24 month-old Fischer-344 rats were cannulated and loaded with Fura 2. Diameter and calcium responses to increasing pressure were measured in HEPES, during NOS inhibition (L-NAME), and following endothelium removal (E-). Cerebral artery tone (+Endothelium) increased with age. Only at the lowest pressure (20 and 40 mm Hg), was intracellular Ca2+ ([Ca2+]i) greater in arteries from 24 month compared to the other age groups. L-NAME-sensitive constriction increased significantly in arteries from 6 to 20-month-old rats but declined significantly thereafter in arteries from 24-month-old rats. [Ca2+]i was less in arteries from 24 month compared to the other groups after treatment with L-NAME. Another endothelial-derived factor, insensitive to L-NAME, also decreased significantly with age. For example (60 mm Hg), the L-NAME-insensitive constriction decreased from 47 ± 10 µm, 42 ± 5 µm, 21 ± 2 µm, and 3 ± 1 µm in 6, 12, 20, and 24 month-old rats, respectively. Our data suggest that aging alters cerebral artery tone and [Ca2+]i responses through endothelial-derived NOS-sensitive and insensitive mechanisms in rat middle cerebral arteries. The combined effect of greater cerebral artery tone with less endothelium-dependent modulation may in part, contribute to the age-dependent shift in cerebral blood flow autoregulation.
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