TY - JOUR
T1 - Synthesis and evaluation of the cardiovascular effects of two, membrane impermeant, macromolecular complexes of dextran-testosterone
AU - Figueroa-Valverde, Lauro
AU - Luna, Hector
AU - Castillo-Henkel, Carlos
AU - Muñoz-Garcia, Olga
AU - Morato-Cartagena, Tomas
AU - Ceballos-Reyes, Guillermo
N1 - Funding Information:
This work was supported by a grant from Instituto Politecnico Nacional and by CONACyT grants No. 31423-M and G-34998-N, Mexico.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Dextran
KW - Macromolecular sequestration
KW - Non-genomic mechanisms
KW - Testosterone
UR - http://www.scopus.com/inward/record.url?scp=0036235678&partnerID=8YFLogxK
U2 - 10.1016/S0039-128X(02)00011-9
DO - 10.1016/S0039-128X(02)00011-9
M3 - Artículo
SN - 0039-128X
VL - 67
SP - 611
EP - 619
JO - Steroids
JF - Steroids
IS - 7
ER -