Cyclic guanosine monophosphate (cGMP) is a molecular messenger that mediates diverse cellular activities, including cellular division. Rise in cGMP levels increases proliferation of endothelial cells and motor neurons. Therefore, elevating cGMP may enhance neuroprotection and neurorestoration after stroke. Raising cGMP levels can be achieved by either increasing its production or by decreasing its hydrolysis. Activating soluble guanylyl cyclase (by factors such as Nitric Oxide) increases cGMP production. Phosphodiesterase-type 5 (PDE-5) is an enzyme that hydrolyzes cGMP. Thus, inhibiting Phosphodiesterase-type 5 raises the intracellular level of cGMP. Sildenafil, vardenafil, tadalafil, and zaprinast are all members of the PDE-5 inhibitors that have been developed to treat erectile dysfunction. These drugs cause accumulation of cGMP that relaxes the vascular smooth muscle.
Administration of sildenafil 24 hours after stroke markedly raised brain levels of cGMP, evoked neurogenesis, and reduced neurological deficit in both young adult and aged rats. Sildenafil enhances angiogenesis and neurogenesis in both young adult and old ischemic rats.
Sildenafil has been also found to attenuate learning impairment induced by blocking cholinergic muscarinic receptors in rats by modulating NO-cGMP signal transduction, a pathway implicated in age-related cognitive decline such as that seen in Alzheimer's dementia.
Chronic administration of DA-8159, a new PDE-5 inhibitor, in stroke-prone, hypertensive rats increases cerebral blood flow in the ischemic brain, cGMP, plasma Nitric Oxide, and the antioxidative capacity and attenuates endothelial dysfunction.
The Neural Repair Institute is a legal assumed name for Your Biology, NFP
The Neural Repair Institute is a not-for-profit, tax exempt organization under section 501 C 3. All donations are tax-deductible. P.O. Box 437 - Chicago Ridge, IL 60415 - 0437 Tel: 708 - 393 - 6383 Fax: 708 - 496 - 6466 Website: www.neuralrepairinstitute.orgEmail: contact@neuralrepairinstitute.org