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1 Department of Physiology and Pharmacology, Center For Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA
2 Department of Kinesiology and Health Sciences, California State University, San Bernardino, CA 92407, USA
3 Department of Obstetrics and Gynecology, University of Vermont College of Medicine, Burlington, VT 05405, USA
We have shown recently that development from neonatal to adult life affects cerebrovascular tone of mouse cerebral arteries through endothelium-derived vasodilatory mechanisms. The current study tested the hypothesis that development from fetal to adult life affects cerebral artery vascular smooth muscle (VSM) [Ca2+]i sensitivity and tone through a mechanism partially dependent upon endothelium-dependent signalling. In pressurized resistance sized cerebral arteries (
150 µm) from preterm (95 ± 2 days gestation (95 d)) and near-term (140 ± 2 days gestation (140 d)) fetuses, and non-pregnant adults, we measured vascular diameter (µm) and [Ca2+]i (nM) as a function of intravascular pressure. We repeated these studies in the presence of inhibition of nitric oxide synthase (NOS; with L-NAME), cyclo-oxygenase (COX; with indomethacin) and endothelium removal (E–). Cerebrovasculature tone (E+) was greater in arteries from 95 d fetuses and adults compared to 140 d sheep. Ca2+ sensitivity was similar in 95 d fetuses and adults, but much lower in 140 d fetuses. Removal of endothelium resulted in a reduction in lumen diameter as a function of pressure (greater tone) in all treatment groups. [Ca2+]i sensitivity differences among groups were magnified after E–. NOS inhibition decreased diameter as a function of pressure in each age group, with a significant increase in [Ca2+]i to pressure ratio only in the 140 d fetuses. Indomethacin increased tone and increased [Ca2+]i in the 140 d fetuses, but not the other age groups. Development from near-term to adulthood uncovered an interaction between NOS- and COX-sensitive substances that functioned to modulate artery diameter but not [Ca2+]i. This study suggests that development is associated with significant alterations in cerebral vascular smooth muscle (VSM), endothelium, NOS and COX responses to intravascular pressure. We speculate that these changes have important implications in the regulation of cerebral blood flow in the developing organism.
(Received 15 October 2003;
accepted after revision 29 April 2004;
first published online 6 May 2004)
Corresponding author G. G. Geary and others: Department of Kinesiology and Health Sciences, California State University, San Bernardino, CA 92407, USA. Email: ggeary{at}csusb.edu
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