Project Details
Description
It is becoming increasingly apparent that N0, a short-lived reactive
nitrogen intermediate produced by a variety of cell types, plays a
critical role in diverse physiological processes including regulation of
blood pressure, neurotransmission, respiration, gastric motility, renal
function, wound healing, cell growth, and cytotoxicity. Recent studies
have also implicated N0 in the pathogenesis of tissue injury. The
overall objective of this program project is to examine the role of N0
oxide in the pathophysiology of chemical induced tissue injury. The
overall hypothesis that provides a basis for the proposed research of
the program project is that N0 is produced in tissues in excess
quantities following exposure to toxic chemicals and N0 or its oxidation
products can act directly on the tissue to promote injury. As an
alternative to the latter hypothesis, it is postulated that N0 may protect
the tissue from injury by scavenging reactive oxygen intermediates.
Thus, the role of N0 in toxicity may depend on the specific toxicant,
the target tissue and the extent to which reactive oxygen intermediates
are involved in tissue injury. The program project consists of five
projects aimed at addressing various aspects of this hypothesis. These
include: Pharmacologic Regulation of Nitric Oxide; Novel Mechanisms
Regulating Nitric Oxide in the Skin; Astrocytic Oxide an Glial
Function; Regulation of Nitric Oxide Synthesis and Toxicity by
Osteopontin; and, Role of Nitric Oxide in Tetrachlorodibenzo-p-dioxin
(TCCD)-Mediated Toxicity. A strong chemistry support laboratory has
been organized and is integral to each project for expertise in
analytical chemistry and for the development and production of novel
inhibitors of N0 synthetase that will be used by the program's
research groups. The key to the successful of this program project will
be to integrate the knowledge gained in these studies into a cohesive
model to explain the contribution of nitric oxide to chemical-induced
toxicity.
Status | Finished |
---|---|
Effective start/end date | 9/15/97 → 8/31/04 |
Funding
- National Institute of Environmental Health Sciences: $1,017,690.00
- National Institute of Environmental Health Sciences: $1,058,394.00
- National Institute of Environmental Health Sciences: $76,145.00
ASJC
- Physiology
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.