Cerebral Microcirculatory Effects of Maturation

<p>The present studies demonstrate that in the second (2B) and fourth (4B) branches of newborn and adult sheep middle cerebral arteries, 5-HT2 serotonergic receptors mediate contractile responses to serotonin and that alpha-1 adrenergic receptors mediate contractile responses to norepinephrine. In addition, tissue sensitivity to 5-HT and NE decreases significantly with maturation, but does not vary with branch order. These age-related changes were associated with a decrease in affinity and maximum response in 2B and 4B segments of 5-HT and NE contracted arteries, respectively. Norepinephrine and 5-HT occupancy at the pD₂ rose significantly in 2B segments, but did not change with age in 4B segments of NE contracted arteries and decreased significantly in 2B segments of 5-HT contracted arteries. Together these changes suggest that in 5-HT and NE contracted arteries differences in sensitivity and maximum response are secondary to changes in affinity and occupancy, although other factors are necessary to fully explain the changes in NE and 5-HT responsiveness. The maturation of cerebral arteries is also associated with significant changes in the mechanisms regulating cerebrovascular responses to hypoxia. Our findings suggest that age-related differences in electrophysiological characteristics reside in the small resistance arteries where most vascular regulation occurs. These studies demonstrate a role for K_ATPchannels in hypoxic vasodilatation, which is larger, yet, less sensitive in newborns than in adults. Accordingly, our studies also define a glyburide-resistant but depolarization-sensitive relaxant component of the response to hypoxia, that appears to represent K_Ca channels, which is of greater magnitude than the K_ATPchannel component, and plays a greater role in adult than in newborn responses to hypoxia. Additionally, these studies reveal a potent contractile response to hypoxia in arteries contracted by potassium depolarization which was of greater magnitude in adults than in newborns. In conclusion, the present studies suggest that differences in contractility of sheep middle cerebral arteries, which vary by age and branch order, involve changes in affinity, occupancy, sensitivity and maximum response. In addition, the direct effects of hypoxia appear to be multifactorial and appear to involve KATP and KCa channels in addition to other as yet unidentified components.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Pharmacology

Year

1994

Author dc:creator

• Elliott, Scott R.

Contributors dc:contributor

• William J. Pearce
• Raymond D. Gilbert
• Marvin Peters
• Ralph E. Purdy
• Lubo Zhang

• Animal Experimentation and Research
• Biological Factors
• Circulatory and Respiratory Physiology
• Organic Chemicals
• Pharmacology
• Sheep and Goat Science
• Cerebral Arteries; Norepihephrine -- pharmacology; Serotonin -- pharmacology; Age Factors; Anoxia -- complications

Statement dc:rights

• This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Language dc:language

English

Repository record dc:identifier

https://scholarsrepository.llu.edu/etd/1483

OAI identifier oai:identifier

oai:scholarsrepository.llu.edu:etd-2259