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1 Physiology and Pharmacology and Institute for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California, United States
* To whom correspondence should be addressed. E-mail: jbuchholz{at}llu.edu.
Although postnatal maturation modulates agonist-induced cerebrovascular contractility, its effects on the mechanisms mediating cerebrovascular myogenic tone remain poorly understood. Because regulation of calcium influx and myofilament calcium sensitivity change markedly during early postnatal life, the present study tested the hypothesis that early postnatal maturation increases the pressure-sensitivity of cerebrovascular myogenic tone via age-dependent enhancement of pressure-induced calcium mobilization and myofilament calcium sensitivity. Pressure-induced myogenic tone and changes in artery wall intracellular calcium concentrations ([Ca2+]i) were measured in endothelium denuded, fura-2 loaded middle cerebral arteries (MCA) from pup (P14) and adult (6 months old) Sprague-Dawley rats. Increases in pressure from 20 to 80 mm Hg enhanced myogenic tone in MCA from pups and adults although the normalized magnitudes of these increases were significantly greater in pup than adult MCA. At each pressure step, vascular wall [Ca2+]i was greater in pup than in adult MCA. Nifedipine attenuated pressure-evoked constrictions in pup MCA and eliminated responses to pressure in the adult MCA. Pup and adult MCA exhibited pressure-dependent increases in calcium sensitivity, as estimated by changes in the ratio of pressure-induced myogenic tone to wall [Ca2+]i. However, there were no differences in the magnitudes of these increases between pup and adult MCA. The results suggest that regardless of postnatal age, changes in calcium influx and myofilament calcium sensitivity contribute to the regulation of cerebral artery myogenic tone. Greater cerebral myogenic response in P14 compared to adult MCA is due to greater pressure-induced increases in [Ca2+]i, rather than enhanced augmentation of myofilament calcium sensitivity.
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