Testosterone Replacement Therapy Prevents Alterations of Coronary Vascular Reactivity Caused by Hormone Deficiency Induced by Castration.

The present study aimed to determine the effects of chronic treatment with different doses of testosterone on endothelium-dependent coronary vascular reactivity in male rats. Adult male rats were divided into four experimental groups: control (SHAM), castrated (CAST), castrated and immediately treated subcutaneously with a physiological dose (0.5 mg/kg/day, PHYSIO group) or supraphysiological dose (2.5 mg/kg/day, SUPRA group) of testosterone for 15 days. Systolic blood pressure (SBP) was assessed at the end of treatment through tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed using the Langendorff retrograde perfusion technique. A dose-response curve for bradykinin (BK) was constructed, followed by inhibition with 100 μM L-NAME, 2.8 μM indomethacin (INDO), L-NAME + INDO, or L-NAME + INDO + 0.75 μM clotrimazole (CLOT). We observed significant endothelium-dependent, BK-induced coronary vasodilation, which was abolished in the castrated group and restored in the PHYSIO and SUPRA groups. Furthermore, castration modulated the lipid and hormonal profiles and decreased body weight, and testosterone therapy restored all of these parameters. Our results revealed an increase in SBP in the SUPRA group. In addition, our data led us to conclude that physiological concentrations of testosterone may play a beneficial role in the cardiovascular system by maintaining an environment that is favourable for the activity of an endothelium-dependent vasodilator without increasing SBP

Vasodilator response to increasing concentrations of bradykinin (BK: 0.1–1,000 ng).

<p>Before (A) and after inhibition with L-NAME (B), indomethacin (INDO) (C); L-NAME + INDO (D), and L-NAME + INDO + clotrimazole (E). The values are expressed as the mean ± SEM. * p<0.05 compared with the SHAM group, #p<0.05 compared with the CAST group, +p<0.05 compared with the PHYSIO group, and §p <0.05 compared with the SUPRA group.</p

Hormone level.

<p>Testosterone in the SHAM (n = 15), CAST (n = 15); PHYSIO (n = 17), and SUPRA (n = 16) groups. Data are expressed as the mean ± SEM. * p<0.05 compared with the SHAM group, #p<0.05 compared with the CAST group, and +p<0.05 compared with the PHYSIO group.</p

Lipid profile of normotensive rats.

<p>A) Triglycerides, B) total cholesterol, C) very-low-density lipoproteins (VLDL), D) low-density lipoprotein (LDL) cholesterol, and E) high-density lipoprotein (HDL) cholesterol in the SHAM (n = 15), CAST (n = 17), PHYSIO (n = 17), and SUPRA (n = 16) groups. Data are expressed as the mean ± SEM. *p<0.05 compared with the SHAM group, #p<0.05 compared with the CAST group.</p

Systolic blood pressure of normotensive rats.

<p>SHAM (n = 15), CAST (n = 15), PHYSIO (n = 21), and SUPRA (n = 15) groups. The values are expressed as the mean ± SEM. * p<0.05 compared with the SHAM group, #p<0.05 compared with the CAST group, and +p <0.05 compared with the PHYSIO group.</p

Body weight and relationship of the dry weight of the heart chambers with body weight in the SHAM, CAST, SUPRA, and PHYSIO groups after 15 days of treatment with testosterone.

<p>The values are expressed as the mean ± SEM.</p><p>* p<0.05 compared with the SHAM group.</p><p>Body weight and relationship of the dry weight of the heart chambers with body weight in the SHAM, CAST, SUPRA, and PHYSIO groups after 15 days of treatment with testosterone.</p

Baseline coronary perfusion pressure (CPP) of normotensive rats.

<p>SHAM (n = 20), CAST (n = 23), PHYSIO (n = 20), and SUPRA (n = 23) groups. The values are expressed as the mean ± SEM.</p

Coronary perfusion pressure (CPP, mmHg) in normotensive rats after inhibition with 100 μM L-NAME, 28 μM indomethacin (INDO), L-NAME + INDO, or L-NAME + INDO + 0.75 μM clotrimazole.

<p>The values are expressed as the mean ± SEM.</p><p>* p<0.05 compared with the respective controls.</p><p>Coronary perfusion pressure (CPP, mmHg) in normotensive rats after inhibition with 100 μM L-NAME, 28 μM indomethacin (INDO), L-NAME + INDO, or L-NAME + INDO + 0.75 μM clotrimazole.</p

Probiotic treatment with Kefir reduces vascular oxidative stress while suppressing COX2 mediated relaxation in intestinal arteries of an animal model of menopause

284-289Functional foods such as probiotics are known to have benefits in various diseases including metabolic disorders and cardiovascular disease (CVD). In women, CVD has been shown to be linked with their gut microbiota and hormones. Here, we have evaluated the effects of chronic Kefir, a fermented milk beverage in Russia, Central Asia, Middle East and Eastern Europe, on mesenteric artery, using an animal model of menopause focusing on the superoxide anion and COX2 pathways. Two-month-old female Wistar rats were ovariectomized and treated by gavage with Kefir (5 % w/v, 3 mL/kg/day) or milk (Control) during two months. After this period, third-order mesenteric artery segments were isolated and mounted in a myograph system for evaluation of concentration-response curves to acetylcholine. We performed western blot analyses and measured oxidative stress through dihydroethidium (DHE) staining. Kefir reduced vascular oxidative stress, despite not changing SOD2 levels. COX2 levels were not changed by kefir, despite an apparent tendency towards reduction. However, in the functional experiments, under incubation with a COX2 inhibitor, a suppression of this pathway was observed in the kefir group, which suggests an interaction between inflammatory pathways and oxidative stress in this model. The effect of acute incubation with a superoxide anion scavenger on vascular responsiveness was equal in both groups. Kefir reduces vascular oxidative stress levels while suppressing COX2-mediated relaxation in mesenteric vessels in an animal model of menopause; which appears to involve an interplay between these two factors

Obesity, inflammation, and exercise training: relative contribution of iNOS and eNOS in the modulation of vascular function in the mouse aorta

Background - The understanding of obsesity-related vascular dysfunction remains controversial mainly because of the diseases associated with vascular injury. Exercise training is known to prevent vascular dysfunction. Using an obesity model without comorbidities, we aimed at investigating the underlying mechanism of vascular dysfunction and how exercise interferes with this process.Methods - High-sugar diet was used to induce obesity in mice. Exercise training was performed 5 days/week. Body weight, energy intake, and adipose tissues were assessed; blood metabolic and hormonal parameters were determined; and serum TNFα was measured. Blood pressure and heart rate were assessed by plethysmography. Changes in aortic isometric tension were recorded on myograph. Western blot was used to analyze protein expression. Nitric oxide (NO) was evaluated using fluorescence microscopy. Antisense oligodeoxynucleotides were used for inducible nitric oxide synthase isoform (iNOS) knockdown.Results - Body weight, fat mass, total cholesterol, low-density lipoprotein cholesterol fraction, insulin, and leptin were higher in the sedentary obese group (SD) than in the sedentary control animals (SS). Exercise training prevented these changes. No difference in glucose tolerance, insulin sensitivity, blood pressure, and heart rate was found. Decreased vascular relaxation and reduced endothelial nitric oxide synthase (eNOS) functioning in the SD group were prevented by exercise. Contractile response to phenylephrine was decreased in the aortas of the wild SD mice, compared with that of the SS group; however, no alteration was noted in the SD iNOS-/- animals. The decreased contractility was endothelium-dependent, and was reverted by iNOS inhibition or iNOS silencing. The aortas from the SD group showed increased basal NO production, serum TNFα, TNF receptor-1, and phospho-IκB. Exercise training attenuated iNOS-dependent reduction in contractile response in high-sugar diet–fed animals, decreased iNOS expression, and increased eNOS expression.Conclusion - Obesity caused endothelium dysfunction, TNFα, and iNOS pathway up-regulation, decreasing vascular contractility in the obese animals. Exercise training was an effective therapy to control iNOS-dependent NO production and to preserve endothelial function in obese individuals