# CEREBROVASCULAR ADAPTATIONS TO LONG-TERM HYPOXIA

> **NIH NIH R01** · LOMA LINDA UNIVERSITY · 1993 · $286,034

## Abstract

The overall purpose of this study is to explore the mechanisms by which the
cerebrovascular system adapts to long-term hypoxemia.  Our overall
hypothesis is that the changes in cerebrovascular reactivity in high-
altitude acclimatized fetuses and adults are secondary to alterations in
the basic cellular and biochemical mechanisms which regulate vascular
function.  Specifically, we shall test three hypotheses as follows:  I. The
catecholamine hypothesis proposes that changes in cerebrovascular
catecholamine metabolism (norepinephrine and/or reuptake) are associated
with the vascular reactivity changes in response to long-term hypoxemia.
II. The alpha receptor hypothesis suggests that alterations in
cerebrovascular alpha receptor types (alpha 1 and/or alpha 2), number, or
receptor gain (i.e., the magnitude of the second messenger inositol
triphosphate response) account for the reactivity changes.  III. The
structural protein hypothesis suggests that changes int he cerebrovascular
structural proteins collagen and/or elastin account for these changes.
Each of these hypotheses will be examined in three experimental groups:
term fetus, pregnant adult, and nonpregnant adult.  Each of these groups
will include two subgroups:  normoxic controls and high altitude
acclimatized animals.  Thus, there will be a total of six experimental
groups in which cerebrovascular changes will be studied to test each
hypothesis.  To the common carotid, basilar, posterior communicating, and
middle cerebral arteries, we will measure 1) concentrations of
catecholamines and their metabolites, 2) norepinephrine uptake, 3) alpha 1
and alpha 2 receptor direct binding, 4) receptor binding by quantitative
autoradiography, 5) receptor dose-response relations, 6) receptor gain,
inositol triphosphate (IP3) concentrations, 7) vascular reactivity, 8)
elastin and collagen concentrations.  Taken as a whole, the studies have
potential for new and important insights into the basic mechanisms of the
brain's defenses to hypoxia, e.g., specific receptor function, signal
transduction, and vascular smooth muscle function.  The proposed studies
will lead to greater insights into the regulation of cerebral vascular
reactivity per se, and the pathophysiology of clinical problems associated
with the dysregulation of cerebral blood flow, intracerebral hemorrhage,
various neurological sequelae (such as cerebral palsy, seizure disorders,
and mental retardation, minimal brain dysfunction, et cetera), as well as
for a deeper understanding of the adaptations which serve to maintain fetal
oxygen availability under such a stress.  In addition, they will provide a
deeper understanding of the physiologic basis of hypoxic-induced
acclimatization responses in general, and the basis of the vascular
responses during the course of development and in women during pregnancy.

## Key facts

- **NIH application ID:** 2194821
- **Project number:** 5R01HD003807-24
- **Recipient organization:** LOMA LINDA UNIVERSITY
- **SAM.gov UEI:** SZAKFNU35ZX5
- **Principal Investigator:** LAWRENCE D LONGO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $286,034
- **Award type:** 5
- **Project period:** 1978-02-01 → 1997-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194821

## Citation

> US National Institutes of Health, RePORTER application 2194821, CEREBROVASCULAR ADAPTATIONS TO LONG-TERM HYPOXIA (5R01HD003807-24). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2194821. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*