Integral Effects of Systemic Nitric Oxide Synthase Inhibition on Carotid Arterial Compliance

Decreased arterial compliance (increased arterial stiffness) is associated with cardiovascular events. Nitric oxide regulates vascular tone, which can influence arterial compliance. We previously investigated the effects of systemic nitric oxide synthase (NOS) inhibition on arterial compliance under the systemic α-adrenergic receptor blocking. In the present study, we investigated the effect of systemic NOS inhibition alone on central arterial compliance (via carotid arterial ultrasound imaging and applanation tonometry). Eighteen apparently healthy young adults (26±1 years) underwent intravenous infusions of NG-monomethyl-L-arginine (L-NMMA) or placebo (saline) on separate days. In the placebo control condition, no significant changes were observed in mean arterial pressure, cross-sectional compliance, and β-stiffness index. Mean arterial pressure increased significantly (84±2 vs. 96±3 mmHg) after the administration of L-NMMA, whereas there were no significant changes in cross-sectional compliance (0.11±0.01 vs. 0.12±0.01 mm2/mmHg), β-stiffness index (6.44±0.37 vs. 5.51±0.41 unit), or isobaric arterial compliance. Theses results in young healthy adults are not consistent with the idea that carotid arterial compliance is modulated by nitric oxide. Grant Support: This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (18300215, 18650186), JSPS Postdoctoral Fellowships for Research Abroad, and NIH grant AG20966

DHEA administration and exercise training improves insulin resistance in obese rats

Background: Dehydroepiandrosterone (DHEA) is precursor of sex steroid hormone. We demonstrated that acute DHEA injection to type 1 diabetes model rats induced improvement of hyperglycemia. However, the effect of the combination of DHEA administration and exercise training on insulin resistance is still unclear. This study was undertaken to determine whether 6-weeks of DHEA administration and/or exercise training improve insulin resistance in obese male rats. Methods: After 14 weeks of a high-sucrose diet, obese male Wistar rats were assigned randomly to one of four groups: control, DHEA administration, exercise training, and a combination of DHEA administration and exercise training (n = 10 each group). Results: After 6-weeks of DHEA administration and/or exercise training, rats in the combination group weighed significantly less and had lower serum insulin levels than rats in the other groups. Moreover, the rats treated with DHEA alone or DHEA and exercise had significantly lower fasting glucose levels (combination, 84 ± 6.5 mg/dL; DHEA, 102 ± 9.5 mg/dL; control, 148 ± 10.5 mg/dL). In addition, insulin sensitivity check index showed significant improvements in the combination group (combination, 0.347 ± 0.11; exercise, 0.337 ± 0.16%; DHEA, 0.331 ± 0.14; control, 0.308 ± 0.12). Muscular DHEA and 5α-dihydrotestosterone (DHT) concentrations were significantly higher in the combination group, and closely correlated with the quantitative insulin-sensitivity check index (DHEA: r = 0.71, p < 0.01; DHT: r = 0.69, p < 0.01). Conclusion: These results showed that a combination of DHEA administration and exercise training effectively improved fasting blood glucose and insulin levels, and insulin sensitivity, which may reflect increased muscular DHEA and DHT concentrations

Plasma Pentraxin 3 Concentration Increases in Endurance-Trained Men

Introduction: Pentraxin 3 (PTX3), which is mainly produced by endothelial cells, macrophages, and smooth muscle cells in the atherosclerotic region, has a cardioprotective effect. Endurance exercise training has also been known to offer cardioprotection. However, the effect of regular endurance exercise on PTX3 is unknown. This study aimed to investigate whether plasma PTX3 concentrations increase in endurance-trained men. Ten young endurance-trained men and 12 age- and gender-matched sedentary controls participated in this study.Methods: We measured plasma PTX3 concentrations of the participants in each group. We also determined systemic arterial compliance (SAC) by using simultaneous M-mode ultrasound and arterial applanation tonometry of the common carotid artery and used HDL cholesterol (HDLC) as an index of cardioprotective effect.Results: Maximal oxygen uptake was significantly higher in the endurance-trained men than that in the sedentary controls. SAC and HDLC were significantly higher in the endurance-trained men than that in the sedentary controls (SAC = 1.74 ± 0.11 vs 1.41 ± 0.09 mL·mm Hg−1, P < 0.05; HDLC = 70 ± 5 vs 57 ± 4 mg·dL−1, P < 0.05). Plasma PTX3 concentrations were markedly higher in the endurance-trained men than that in the sedentary controls (0.93 ± 0.11 vs 0.68 ± 0.06 ng·mL−1, P < 0.05). Relationships between plasma PTX3 concentrations and SAC and HDLC were linear.Conclusions: This is the first study revealing that endurance-trained individuals had higher levels of circulating PTX3 than sedentary controls. PTX3 may play a partial role in endurance exercise training-induced cardioprotection

Habitual aerobic exercise increases plasma pentraxin 3 levels in middle-aged and elderly women

Chronic inflammation that occurs with aging is one of the risk factors for cardiovascular disease. Regular exercise may prevent cardiovascular morbidity by decreasing chronic systematic inflammation. Additionally, excess inflammation can be reduced by the anti-inflammatory protein pentraxin 3 (PTX3). Thus, both habitual exercise and PTX3 have an anti-inflammatory effect. However, it is unclear whether regular exercise leads to increased plasma PTX3 concentration. In the present study, we investigated the effects of regular aerobic exercise on plasma PTX3 concentration in middle-aged and elderly women. Twenty-two postmenopausal women (60 ± 6 years) were randomly divided evenly into 2 groups (i.e., exercise intervention and control). Subjects in the exercise group completed 2 months of regular aerobic exercise training (walking and cycling, 30-45 min, 3-5 days·week(-1)). Before and after the intervention, we evaluated plasma PTX3 concentration, peak oxygen uptake, blood chemistry, and arterial distensibility (carotid arterial compliance and β-stiffness) in all participants. There were no significant differences in baseline parameters between the 2 groups. Plasma PTX3 concentration was significantly increased in the exercise group after the intervention (p < 0.05). High-density lipoprotein cholesterol, peak oxygen uptake, and arterial compliance were also significantly increased (p < 0.05), while β-stiffness was markedly decreased (p < 0.01) after the intervention. On the other hand, there was no change in the parameters tested in the control group. This study demonstrates that regular aerobic exercise increases plasma PTX3 concentration with improvement of high-density lipoprotein cholesterol, peak oxygen uptake, and arterial distensibility in postmenopausal women

Arterial Stiffness, Physical Activity, and Atrial Natriuretic Peptide Gene Polymorphism in Older Subjects

An increase in arterial stiffness with advancing age is associated with several pathological states, includinghypertension and arteriosclerosis. Regular exercise improves the aging-induced increase in arterial stiffnessand has a protective effect against these diseases. However, not all individuals respond to exerciseto the same extent. Atrial natriuretic peptide (ANP) is involved in the regulation of basal blood pressure,blood flow, and vascular tone. The present study was designed to clarify whether gene polymorphisms inANP-related genes affect exercise-induced improvements in arterial stiffness. We performed a cross-sectionalstudy of 291 healthy middle-aged and older Japanese subjects (63±1 years), examining the relationshipbetween daily physical activity–induced improvements in arterial stiffness, estimated by brachial-anklearterial pulse wave velocity (baPWV), and the gene polymorphisms of valine32methionine (V32M: 664G>A)in exon 1 of ANP and asparagine521aspartic acid (N521D: 1780A>G) in exon 8 of the ANP clearance receptor(NPR-C). The baseline baPWV was significantly lower in the active group, but no differences were seen inblood pressure. Active subjects with the ANP-VV genotype had significantly lower baPWV and higherplasma ANP levels compared with inactive subjects, but there were no variations related to the VM+MMgenotype. Additionally, baPWV and plasma ANP levels were negatively correlated in ANP-VV genotypesubjects, but were not correlated in VM+MM individuals. Our results suggest that ANP polymorphismin older Japanese subjects may affect the cardiovascular response to regular exercise