Effect of doxazosin on cholesterol synthesis in cell culture

Journal Article · Sun Jan 01 04:00:00 EST 1989 · J. Cardiovasc. Pharmacol.; (United States)

DOI:https://doi.org/10.1097/00005344-198900132-00002· OSTI ID:5723176

D'Eletto, R D; Javitt, N B

The effect of doxazosin on cholesterol synthesis was determined by measuring the content of deuterium-enriched cholesterol in rabbit fibroblasts with and without receptors for low-density lipoproteins (LDL) and in hepatoma (Hep G2 cells). Doxazosin, at concentrations of 5-20 mumol/L, increased LDL binding to hepatic cells in a dose-related manner. Also, in these hepatic cells, doxazosin produced dose-related decreases in both newly synthesized cholesterol and cholesterol ester. In rabbit fibroblasts that were LDL receptor negative, de novo cholesterol synthesis was markedly reduced by increasing concentrations of doxazosin. Taken together, these results suggest that doxazosin may have a direct inhibitory effect on cholesterol synthesis independent of the LDL receptor. The inhibition of cholesterol synthesis by doxazosin may cause cells to compensate by upregulating the LDL receptor, thereby increasing the importation of lipoprotein cholesterol and reducing LDL cholesterol in the medium. This hypothesis supports findings in the clinical setting whereby doxazosin has a beneficial effect on the lipid profile, and suggests a useful additional property for this antihypertensive agent.

• Research Organization: New York Univ. Medical Center, NY (USA)
• OSTI ID: 5723176
• Journal Information: J. Cardiovasc. Pharmacol.; (United States), Journal Name: J. Cardiovasc. Pharmacol.; (United States) Vol. 13 Suppl 2; ISSN JCPCD
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANTIHYPERTENSIVE AGENTS
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
CARDIOVASCULAR AGENTS
CELL CULTURES
CHOLESTEROL
CONNECTIVE TISSUE CELLS
DEUTERIUM
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
FIBROBLASTS
HEPATOMAS
HYDROGEN ISOTOPES
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
LIPIDS
LIPOPROTEINS
MEMBRANE PROTEINS
NEOPLASMS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PROTEINS
REACTION KINETICS
RECEPTORS
SOMATIC CELLS
STABLE ISOTOPES
STEROIDS
STEROLS
SYNTHESIS
TRACER TECHNIQUES
TUMOR CELLS