Name: LETÍCIA TINOCO GONÇALVES
Publication date: 15/02/2023
Examining board:
Name |
Role |
|---|---|
| ROGER LYRIO DOS SANTOS | Advisor |
Summary: The abusive use of testosterone is considered a global public health problem, with
several side effects. In the cardiovascular system, its effects are still controversial,
ranging from protective to deleterious actions. Because testosterone is a hormone that
can be converted to 17 -estradiol and dihydrotestosterone (DHT), part of the effects
found with supraphysiological doses can be attributed to its metabolites. Therefore,
we investigated the hypothesis that a supraphysiological dose of testosterone impairs
the endothelium-dependent vasodilation of mesenteric resistance arteries, as well as
its repercussions on oxidative stress (OS) and blood pressure (BP). We also evaluated
the participation of 17 -estradiol and DHT in the responses found. We used
Spontaneously Hypertensive Rats (SHR), aged 8 to 10 weeks, divided into 5 groups:
intact (SHAM), orchiectomized (ORX), intact testosterone-treated (TTO; 3
mg/Kg/day/s.c.), intact treated with testosterone and anastrozole [aromatase enzyme
inhibitor (TTO+ANA; 0.1 mg/Kg/day)] and intact treated with testosterone and
finasteride [5-reductase enzyme inhibitor (TTO+FIN; 5 mg/Kg/day)] for 4 weeks.
BP was assessed by tail cuff plethysmography. We performed concentration-response
curves to acetylcholine (ACh, 0.1 nM - 10 M) in mesenteric arteries using a wire
myograph, in the absence and presence of pharmacological inhibitors. Also
testosterone, 17 -estradiol and dihydrotestosterone concentrations were evaluated.
Vascular detection of superoxide anion (O2
•-
) and endothelium ultrastructure were
analyzed by DHE and scanning electron microscopy (SEM), respectively. Data were
expressed as mean ± standard error of the mean, and analyzed by Student's t-test or
one-way or two-way ANOVA, followed by Tukey's post hoc test (p < 0.05).
Orchiectomy reduced levels of testosterone, 17 -estradiol and dihydrotestosterone,
impaired ACh vasodilation, increased OS, altered endothelial morphology without
altering BP. Testosterone treatment did not impair ACh vasodilation compared to the
SHAM group, however it altered the endothelial pathways of relaxation, with lesser
participation of NO and greater participation of prostanoids, possibly derived from
COX-1. In addition, in the TTO group, the participation of EDH was greater
compared to SHAM, indicating that EETs, H2O2 and K+
channels contributed to this
vasodilator response. In the TTO+ANA group, the reduction in 17 -estradiol levels
did not impair ACh vasodilation, however, it decreased the participation of nitric
oxide, prostanoids and increased EDH, and increased O2•-
levels with alteration of
endothelial morphology. TTO+FIN showed impairment in the vasodilator response to
ACh, with an increased participation of NO and a lower participation of prostanoids.
Regarding EDH, with a decrease in dihydrotestosterone, there was no increase in the
participation of EETs, H2O2 and K+ channels compared to TTO. DHT seems to
contribute to the decrease of NO and estrogen seems to stimulate the action of the NO
pathway and prostanoids. In estrogen reduction, testosterone maintains endothelial
vasodilation by greater stimulation of EDH, with more action of EETs, H2O2 and K+
channels, with greater formation of O2
•-
. These results may contribute to the
elucidation of the modulating role of testosterone on endothelial function, even in
treatment with a supraphysiological dose, in addition to showing the importance of
the presence of estrogen for the cardiovascular system in situations of endothelial
dysfunction.
