Glycyrrhetinic acid attenuates vascular smooth muscle vasodilatory function in healthy humans.

Abnormal glucocorticoid metabolism contributes to vascular dysfunction and cardiovascular disease. Cortisol activation of vascular mineralocorticoid and glucocorticoid receptors is regulated by two types of 11beta-HSD (11-beta hydroxysteroid dehydrogenase), namely 11beta-HSD2 and 11beta-HSD1 (type 2 and type 1 11beta-HSD respectively). We hypothesized that inhibition of 11beta-HSD would attenuate vascular function in healthy humans. A total of 15 healthy subjects were treated with the selective 11beta-HSD inhibitor GA (glycyrrhetinic acid) or matching placebo in a randomized double-blinded cross-over trial. 11beta-HSD activity was assessed by the urinary cortisol/cortisone ratio, and vascular function was measured using strain-gauge plethysmography. Endothelial function was measured through incremental brachial artery administration of methacholine (0.3-10 microg/min) and vascular smooth muscle function with incremental verapamil (10-300 microg/min). GA increased the 24-h urinary cortisol/cortisone ratio compared with placebo (P=0.008). GA tended to reduce the FBF (forearm blood flow) response to methacholine (P=0.09) and significantly reduced the FBF response to verapamil compared with placebo (P=0.04). MAP (mean arterial pressure) did not differ between the study conditions. 11beta-HSD inhibition attenuated vascular smooth muscle vasodilatory function in healthy humans. Disturbances in cortisol activity resulting from 11beta-HSD inactivation is therefore a second plausible mechanism for mineralocorticoid-mediated hypertension in humans.

Emergency department arrival times, treatment, and functional recovery in women with acute ischemic stroke.

BACKGROUND: Sex disparities have been well documented in patients with ischemic stroke. Previous studies have suggested that female sex is a risk factor for delay in arrival time to the emergency department (ED) and may contribute to ineligibility for thrombolytic therapy. With the increase in education efforts targeting women, we investigated whether ED arrival times, rates of thrombolytic use, and functional outcomes continue to differ in men and women with acute ischemic stroke (AIS). METHODS: This study was a retrospective database analysis of patients with AIS (2001-2008). All AIS patients presenting within 24 hours with a known time of symptom onset and a documented admission National Institutes of Health Stroke Scale (NIHSS) were included. The Modified Barthel Index (MBI) assessed patients' functional status preadmission (historical), admission, and at 3 and 12 months poststroke. RESULTS: Included in the analysis were 480 (50.6%) women and 468 (49.4%) men. Women were significantly older than men (70.6 +/- 0.7 vs. 65.3 years +/- 0.6, p