The present study focused on the main hypothesis that maturation decreases contractile reliance on calcium influx and myofilament Ca2+ sensitivity, and increases reliance on release of calcium from intracellular stores to develop and maintain pressure-evoked myogenic tone in rat cerebral blood vessels. To test this hypothesis, pressure-induced myogenic tone and changes in artery wall ([Ca2+]i) were measured simultaneously in isolated endothelium denuded, fura-2 loaded middle cerebral arteries (MCA) from pup (PI4) and adult (6 months old) SD rats. We studied the mechanism that govern myogenic tone and examined the hypothesis that during maturation, MCA from rat pups are more reliant on calcium influx and myofilament calcium sensitivity to maintain pressure-evoked myogenic constriction as compared to adults. The results support the view that the greater cerebral myogenic response in P14 compared to adult MCA appears due to greater pressure-induced increases in [Ca ]i, rather than enhanced increases of calcium sensitivity. We also tested whether MCA rely more on calcium release from intracellular stores to develop pressure-evoked myogenic constriction as compared to immature MCA. Measurements were done in calcium replete HEPES buffer in the absence and presence of, cyclopiazonic acid (CPA) to deplete [Ca2+]i stores or with the calcium channel blocker, lanthanum (La ), or with La plus CPA. The results demonstrated that release of calcium from intracellular stores is necessary for the development of pressure-evoked myogenic tone in the adult rat cerebrovasculature more so than in the pup. Experiments were also done to determine whether MCA from rat pups is more reliant on myofilament calcium sensitivity, in a permeabilized preparation, to maintain pressure-evoked myogenic constriction as compared to adults. We measured pressure-evoked myogenic tone in endothelial denuded segments of MCA from P14 and adult rats that where permeabilized using (3-escin. The results suggest that perfusion 9-1- pressures increases Ca sensitivity only in pups cerebral arteries. The overall results show that mature cerebral arteries are regulated by both calcium influx and release from intracellular stores to maintain pressure-evoked myogenic tone, while immature cerebral arteries rely to a greater degree on calcium influx and myofilament calcium sensitivity for the development and maintain of pressure-evoked myogenic tone.
John N. Buchholz
Marilyn J. Cipolla
Lawrence D. Longo
William J. Pearce
Doctor of Philosophy (PhD)
Year Degree Awarded
Date (Title Page)
Library of Congress/MESH Subject Headings
Vasoconstriction -- physiology; Cerebrovascular Circulation -- physiology; Cerebral Arteries -- pharmacology; Blood Vessels -- physiology; Blood Flow Velocity; Myogenic Regulatory Factors; Muscle, Smooth, Vascular -- metabolism; Calcium Channels -- metabolism; Actin Cytoskeleton -- drug effects; Rats; Models, Animal; Retrospective Studies.
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Charles, Shelton M., "Postnatal Maturation Modulates Cerebrovascular Myogenic Tone" (2009). Loma Linda University Electronic Theses, Dissertations & Projects. 1111.
Loma Linda University Electronic Theses and Dissertations
Loma Linda University. Del E. Webb Memorial Library. University Archives