Abstract-Sympathetic vasoconstriction is attenuated in exercising muscle by locally generated vasodilators, including NO. Skeletal muscle also produces reactive oxygen species (ROS), such as superoxide (O 2 Ϫ ), which inactivates NO. We, therefore, hypothesized that excessive ROS production would result in enhanced sympathetic vasoconstriction in exercising muscle. To increase O 2 Ϫ by activating NADPH oxidase, rats underwent chronic infusion of angiotensin II (Ang II) or unilateral renal artery stenosis (2K1C) to increase endogenous Ang II. At rest, sympathetic nerve stimulation (range: 1 to 5 Hz) evoked similar graded decreases in femoral vascular conductance (range, Ϫ34% to Ϫ66%) in rats infused with vehicle, Ang II, or norepinephrine and in 2K1C or sham-operated rats. These sympathetically mediated decreases in femoral vascular conductance were markedly attenuated during hindlimb contraction in the vehicle, norepinephrine, and sham rats (range, Ϫ3% to Ϫ26%) and to a lesser degree in the Ang II (range, Ϫ16% to Ϫ47%) and 2K1C (range, Ϫ16% to Ϫ45%) rats. In muscles from Ang II and 2K1C rats, ROS were elevated and the NADPH oxidase subunit gp91 phox was upregulated. The O 2 Ϫ scavenger tempol restored the normal attenuation of sympathetic vasoconstriction in the contracting hindlimbs of the Ang II and 2K1C rats, but this effect was prevented by pretreatment with an NO synthase inhibitor. Taken together, these data indicate that chronically elevated Ang II increases muscle ROS, which disrupts the normal NO-dependent attenuation of sympathetic vasoconstriction. These findings may have implications for muscle oxidative stress and sympathetic vasoregulation when the renin-angiotensin system is chronically activated. Key Words: angiotensin Ⅲ free radicals Ⅲ sympathetic nervous system Ⅲ vasoconstriction Ⅲ muscles T he sympathetic nervous system plays an essential role in the cardiovascular response to exercise by increasing cardiac contractility and rate, augmenting venous return, and increasing vascular resistances in the viscera and inactive muscles. These adjustments increase cardiac output and redirect it to the active muscles. At the same time, the vasoconstrictor response to sympathetic nerve discharge in the active muscles is attenuated in part by the metabolic consequences of contraction. 1-9 Such attenuation, termed functional sympatholysis, 5 is more pronounced in the distal than in the proximal segments of the microcirculation, 1,9 which may help to optimize intramuscular blood flow distribution while preserving sympathetic control of systemic vascular resistance and blood pressure.NO is proposed to be one of the factors mediating functional sympatholysis, 2,3,8,10,11 although it may not always play an essential role. 2,4 Skeletal muscle, which expresses high levels of the neuronal isoform of NO synthase (NOS; nNOS) and lower levels of endothelial NOS, 12 produces NO at a low basal rate that increases during contraction. [13][14][15] We and others have shown that ␣-adrenergic vasoconstriction is enhanced in...

In exercising skeletal muscle, vasoconstrictor responses to α‐adrenoceptor activation are attenuated in part by nitric oxide (NO) produced by the neuronal isoform of NO synthase (nNOS), which is expressed constitutively in skeletal muscle cells. In skeletal muscle of pregnant animals, nNOS mRNA is upregulated, suggesting that muscle nNOS expression is modulated by the steroid hormone oestrogen. Whether oestrogen‐induced changes in nNOS expression have measurable effects on vasoregulation in skeletal muscle is unknown. In this study, we hypothesized that oestrogen deficiency would reduce muscle nNOS expression, resulting in impaired modulation of sympathetic vasoconstriction in exercising skeletal muscle. Compared to gonadally intact rats, we found that ovariectomized (OVX) rats were characterized by greater sympathetic vasoconstriction in contracting hindlimb and reduced nNOS, but not eNOS, in skeletal muscle. In addition, NOS inhibition resulted in a greater enhancement of sympathetic vasoconstriction in contracting hindlimbs of intact compared to OVX rats. These effects of oestrogen deficiency were prevented by chronic treatment of OVX rats with 17β‐oestradiol, but not with chronic progesterone or acute oestradiol. Further analysis revealed that skeletal muscle nNOS correlated directly with plasma 17β‐oestradiol and inversely with the magnitude of sympathetic vasoconstrictor responses in contracting hindlimbs. These data indicate that NO‐dependent attenuation of sympathetic vasoconstriction in contracting skeletal muscle is impaired in oestrogen‐deficient female rats, and suggest that this impairment may be mediated by reduced skeletal muscle nNOS expression.

In this large, real-world population, XIENCE V demonstrated low event rates at 1 year, with several independent predictors. Early DAPT interruption (≤ 30 days) was the most potent predictor of ST, whereas delayed interruption (>30 days) was not predictive. (XIENCE V Everolimus Eluting Coronary Stent System [EECSS] USA Post-Approval Study; NCT00676520).

The Absorb diabetic substudy suggests efficacy and safety of the Absorb BVS for treatment of patients with diabetes mellitus.

This study investigated the role of lung vagal afferents in the respiratory-related evoked potential (RREP) response to inspiratory occlusions by using double-lung transplant recipients as a lung denervation model. Evoked potential recordings in response to inspiratory occlusions were obtained from 10 double-lung transplant (DLT) recipients with normal lung function and 12 healthy control (Nor) subjects under the attend, ignore, and unoccluded conditions. Results demonstrated that early-latency RREP components (P(1), P(1a), N(f), and N(1)) were not significantly different between the DLT and the Nor groups. The late-latency RREP component (P(3)) was identifiable in all DLT subjects during the attend trial. However, P(3) latency was significantly longer in the DLT group compared with the Nor group. The zero-to-peak amplitude of P(3) was also significantly smaller in the DLT group than that in the Nor group during the attend trial. These results suggest that lung vagal afferents were not essential to elicit RREP responses, but may contribute to the cognitive processing of respiratory stimuli.