Characterization of dynamic changes in vascular reactivity following treatment with carmustine in Sprague-Dawley rats
Carmustine, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), is a highly effective anti-cancer drug and bone marrow suppressant agent in humans and animals. Pilot studies demonstrated that BCNU induced a time- and dose-dependent supersensitivity to norepinephrine (NE) in rat caudal arteries after a single dose. The studies presented in this thesis were performed to determine the mechanism for this supersensitivity. Male Sprague-Dawley rats were administered a single dose of BCNU (25 mg/kg, i.p.) on day 0. On day 7 a proximal section of caudal artery was doubly cannulated and perfused intraluminally with Krebs bicarbonate physiological buffer. These studies demonstrated that the supersensitivity induced by BCNU treatment was pre-junctional. Denervation of caudal arteries with 6-hydroxydopamine led to a significant decrease in the EC/sub 50/ for NE in caudal arteries from control rats but not BCNU treated rats. The EC/sub 50/ for NE in control-denervated arterial segments was not statistically different from BCNU-denervated or BCNU-nondenervated segments. Metabolism of (/sup 3/H) NE to its 5 primary metabolites, as determined by thin layer chromatography, and uptake of (/sup 3/H) NE were significantly lower in caudal arteries taken from BCNU treated rats. These data demonstrate that a pre-junctional mechanism was responsible for vascular supersensitivity to NE after BCNU treatment in caudal arteries from Sprague-Dawley rats.
- Research Organization:
- Oregon State Univ., Corvallis (USA)
- OSTI ID:
- 7023945
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ARTERIES
DYNAMIC FUNCTION STUDIES
NITROSOUREAS
BIOLOGICAL EFFECTS
UPTAKE
TRITIUM COMPOUNDS
METABOLISM
NORADRENALINE
SENSITIVITY
THIN-LAYER CHROMATOGRAPHY
ADRENAL HORMONES
AUTONOMIC NERVOUS SYSTEM AGENTS
BLOOD VESSELS
BODY
CARDIOTONICS
CARDIOVASCULAR AGENTS
CARDIOVASCULAR SYSTEM
CHROMATOGRAPHY
DRUGS
HORMONES
LABELLED COMPOUNDS
NEUROREGULATORS
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
SEPARATION PROCESSES
STEROID HORMONES
SYMPATHOMIMETICS
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