Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes.

Hemorrhagic transformation is an important complication of acute ischemic stroke, particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator, the only approved drug for the treatment of acute ischemic stroke. The objective of the present study was to determine the effects of acute manipulation of potential targets for vascular protection [i.e., NF-κB, peroxynitrite, and matrix metalloproteinases (MMPs)] on vascular injury and functional outcome in a diabetic model of cerebral ischemia. Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), the nonspecific NF-κB inhibitor curcumin, or the broad-spectrum MMP inhibitor minocycline at reperfusion. Poststroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments reduced MMP-9 and hemorrhagic transformation in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment, as indicated by beam-walk performance, modified Bederson scores, and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity, yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline. Uncovering the underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies.

Differential effects of ET(A) and ET(B) receptor antagonism on oxidative stress in type 2 diabetes.

Endothelin (ET-1) is chronically elevated in diabetes. However, role of ET-1 in increased oxidative stress in type 2 diabetes is less clear. This study tested the hypotheses that: 1) oxidative stress markers are increased and total antioxidant capacity is decreased in diabetes, and 2) activation of ET(A) receptors mediates oxidative stress whereas ET(B) receptors display opposing effects. Plasma total antioxidant status (TAS) and 8-isoprostane (8-iso PGF(2alpha)) as well as total nitrotyrosine levels in mesenteric resistance vessels were measured in control Wistar and diabetic Goto-Kakizaki (GK) rats (n=5-10) treated with vehicle, ET(A) antagonist (atrasentan, 5 mg/kg/day), or ET(B) receptor antagonist (A-192621, 15 or 30 mg/kg/day, low and high dose, respectively) for 4 weeks. 8-iso PGF(2alpha) (pg/ml) levels were significantly higher in low dose A-192621 treatment groups of control and diabetic rats than in atrasentan or high-dose A-192621 treated groups. Protein nitration was increased in diabetes and ET(A) receptor antagonism prevented this increase. TAS levels were similar in all experimental groups. Thus, ET-1 contributes to oxidative stress in type 2 diabetes and ET receptor antagonism with atrasentan or A-192612 displays differential effects depending on dose and receptor subtype.

Impact of transcendental meditation on ambulatory blood pressure in African-American adolescents.

The objective of this study was to determine the impact of stress reduction on blood pressure (BP) in adolescents by the Transcendental Meditation (TM) program. African-American adolescents (aged 16.2 +/- 1.3 years) with high normal systolic BP were randomly assigned to either 4-month TM (n = 50) or health education control (n = 50) groups. Ambulatory 24-h BP measures were recorded at pretest, 2- and 4-month post-tests, and 4-month follow-up. Greater decreases in daytime systolic BP (P < .04) and diastolic BP (P < .06) in the TM group compared with the control group across the visits demonstrate a beneficial impact of the TM program in youth at risk for the development of hypertension.