To test the hypothesis that obesity/insulin resistance impairs both endothelium-dependent vasodilation and insulinmediated augmentation of endothelium-dependent vasodilation, we studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of methacholine chloride (MCh) or sodium nitroprusside (SNP) during saline infusion and euglycemic hyperinsulinemia in lean insulin-sensitive controls (C), in obese insulin-resistant subjects (OB), and in subjects with non-insulin-dependent diabetes mellitus (NIDDM). MCh induced increments in LBF were ‫ف‬ 40% and 55% lower in OB and NIDDM, respectively, as compared with C ( P Ͻ 0.05).

The purpose of this study was to examine whether insulin's effect to vasodilate skeletal muscle vasculature is mediated by endothelium-derived nitric oxide (EDNO)

BACKGROUND Blast-related traumatic brain injuries have been common in the Iraq and Afghanistan wars, but fundamental questions about the nature of these injuries remain unanswered. METHODS We tested the hypothesis that blast-related traumatic brain injury causes traumatic axonal injury, using diffusion tensor imaging (DTI), an advanced form of magnetic resonance imaging that is sensitive to axonal injury. The subjects were 63 U.S. military personnel who had a clinical diagnosis of mild, uncomplicated traumatic brain injury. They were evacuated from the field to the Landstuhl Regional Medical Center in Landstuhl, Germany, where they underwent DTI scanning within 90 days after the injury. All the subjects had primary blast exposure plus another, blast-related mechanism of injury (e.g., being struck by a blunt object or injured in a fall or motor vehicle crash). Controls consisted of 21 military personnel who had blast exposure and other injuries but no clinical diagnosis of traumatic brain injury. RESULTS Abnormalities revealed on DTI were consistent with traumatic axonal injury in many of the subjects with traumatic brain injury. None had detectible intracranial injury on computed tomography. As compared with DTI scans in controls, the scans in the subjects with traumatic brain injury showed marked abnormalities in the middle cerebellar peduncles (P<0.001), in cingulum bundles (P = 0.002), and in the right orbitofrontal white matter (P = 0.007). In 18 of the 63 subjects with traumatic brain injury, a significantly greater number of abnormalities were found on DTI than would be expected by chance (P<0.001). Follow-up DTI scans in 47 subjects with traumatic brain injury 6 to 12 months after enrollment showed persistent abnormalities that were consistent with evolving injuries. CONCLUSIONS DTI findings in U.S. military personnel support the hypothesis that blast-related mild traumatic brain injury can involve axonal injury. However, the contribution of primary blast exposure as compared with that of other types of injury could not be determined directly, since none of the subjects with traumatic brain injury had isolated primary blast injury. Furthermore, many of these subjects did not have abnormalities on DTI. Thus, traumatic brain injury remains a clinical diagnosis. (Funded by the Congressionally Directed Medical Research Program and the National Institutes of Health; ClinicalTrials.gov number, NCT00785304.)

We have recently shown that insulin-resistant obese subjects exhibit impaired endothelial function. Here, we test the hypothesis that elevation of circulating FFA to levels seen in insulin-resistant subjects can impair endothelial function. We studied leg blood flow responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (Mch) or the endothelium-independent vasodilator sodium nitroprusside during the infusion of saline and after raising systemic circulating FFA levels exogenously via a low-or high-dose infusion of Intralipid plus heparin or endogenously by an infusion of somatostatin (SRIF) to produce insulinopenia in groups of lean healthy humans.

Peripheral vasodilation occurs early in pregnancy prior to full placentation in association with renal vasodilation and activation of the renin-angiotensin-aldosterone system. Plasma volume expansion occurs early, followed later by increases in ANP concentration, suggesting that ANP increases in response to changes in intravasular volume.