Abstract

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 KATP channels 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 KCa channels, which is of greater magnitude than the KATP channel 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.

LLU Discipline

Pharmacology

Department

Pharmacology

School

Graduate School

First Advisor

William J. Pearce

Second Advisor

Raymond D. Gilbert

Third Advisor

Marvin Peters

Fourth Advisor

Ralph E. Purdy

Fifth Advisor

Lubo Zhang

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

1994

Date (Title Page)

6-2-1994

Language

English

Library of Congress/MESH Subject Headings

Cerebral Arteries; Norepihephrine -- pharmacology; Serotonin -- pharmacology; Age Factors; Anoxia -- complications

Type

Dissertation

Page Count

viii; 123

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage 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.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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