Synthesis and evaluation of the cardiovascular effects of two, membrane impermeant, macromolecular complexes of dextran-testosterone

• Published in: Steroids Vol. 67; no. 7; pp. 611 - 619
• Main Authors: Figueroa-Valverde, Lauro, Luna, Hector, Castillo-Henkel, Carlos, Muñoz-Garcia, Olga, Morato-Cartagena, Tomas, Ceballos-Reyes, Guillermo
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-06-2002; Elsevier Science
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; Cell Membrane Permeability; Dextran; Dextrans - chemistry; Dextrans - pharmacology; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Macromolecular sequestration; Macromolecular Substances; Male; Non-genomic mechanisms; Rats; Steroid hormones. Cholecalciferol derivatives; Testosterone; Testosterone - chemistry; Testosterone - pharmacology; Vascular Resistance - drug effects; Vasodilation - drug effects; Vertebrates: endocrinology; Dextran; Non-genomic mechanisms; Testosterone; Macromolecular sequestration; Macromolecule; Plasma membrane; Cardiovascular disease; Testicular hormone; Permeability; Sex steroid hormone; Mechanism of action; Chemical synthesis
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/S0039-128X(02)00011-9

The incidence of cardiovascular disease is greater in men than in premenopausal women. Testosterone has been considered a significant risk factor for cardiovascular disease, but testosterone’s mechanism of action and its cellular site of action are still not clear. However, it is likely that non-genomic extracellular effects of the hormone are involved. With the aim of providing further information about this phenomenon, two membrane impermeant, macromolecular complexes of testosterone were synthesized and their cardiovascular effects were evaluated. We covalently bound testosterone (through carbon 3 or C-17 functional groups) to dextran (2 MDa) and evaluated its effects on isolated and perfused rat hearts (Langerdorff model). Our results showed that the macromolecular complexes increased vascular resistance similarly to free testosterone and blocked adenosine-induced vasodilatation. These effects were exerted rapidly and possibly through a non-genomic mechanism. Blockade of C-3 or C-17 functional groups by binding to macromolecular dextran induced no qualitative and/or quantitative changes in testosterone-induced effects.