Targeting eNOS for stroke protection.
Nitric oxide (NO) generated by endothelial NO synthase (eNOS) plays a crucial role in vascular function and homeostasis. NO possesses vasodilatory, anti-inflammatory, antithrombotic and antiproliferative properties. Augmentation of NO production increases cerebral blood flow, which can lead to neuroprotection during brain ischaemia. Several modalities that upregulate eNOS expression and/or activity have recently been identified, including HMG-CoA reductase inhibitors (statins), steroid hormones, nutrients and physical activity. They all increase NO bioavailability, leading to enhanced cerebral blood flow and protection from ischaemic stroke. Thus, therapeutic modalities that target eNOS not only serve as preventive measures to reduce stroke incidence but also could represent novel treatment strategies for reducing brain injury during cerebral ischaemia.
Endres
Matthias
M
Department of Neurology, Charité Hospital, Humboldt University, Schumanstrasse 20/21, D-10117 Berlin, Germany. matthias.endres@charite.de
Laufs
Ulrich
U
Liao
James K
JK
Moskowitz
Michael A
MA
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D009043:Motor Activity / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III; D009747:Nutritional Physiological Phenomena / Q000502:physiology; D020521:Stroke / Q000517:prevention & control*; D015854:Up-Regulation / Q000187:drug effects
D012739:Gonadal Steroid Hormones; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III