Endothelin Receptors, Mitochondria and Neurogenesis in Cerebral Ischemia

This would seem to be incredibly important to find out, getting more nitric oxide and increasing blood flow to the brain. I bet nothing will occur because we have NO stroke leadership or stroke strategy. We are completely fucked because we have fucking failures for stroke associations. I weep for your children and grandchildren. Will no one think of the children? Will no one think at all?
http://www.ncbi.nlm.nih.gov/pubmed/26786146 

Gulati A¹.

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Abstract

The ET family consists of three isopeptides (ET-1, ET-2 and ET-3) that produce biological actions by acting on two types of receptors (ETA and ETB). Stimulation of ETA receptors produces potent vasoconstrictor effect, while activation of ETB receptors causes vasodilation by releasing nitric oxide (NO) and prostacyclins. In the central nervous system (CNS) ETA receptors are potent constrictors of the cerebral vasculature and appear to contribute in the causation of cerebral ischemia. ETA receptor antagonists have been found to be effective in animal model of cerebral ischemia; however, clinical studies have shown no efficacy.(Well don't give up, figure out why) Mitochondrial functions are critically important for several neural development processes such as neurogenesis, axonal and dendritic growth, and synaptic formation. ET appears to impair mitochondrial functions through activation of ETA receptors. On the other hand, blocking ETB receptors has been shown to trigger apoptotic processes by activating intrinsic mitochondrial pathway. Mitochondria are important for their role in molecular regulation of neurogenesis and angiogenesis. Stimulation of ETB receptors in the adult ischemic brain has been found to promote angiogenesis and neurogenesis mediated through vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). It will be interesting to investigate the effect of ETB receptor stimulation on mitochondrial functions in the CNS following cerebral ischemia. In the CNS stimulation of ETB receptors has a beneficial effect in animal models of stroke. Since angiogenesis and neurogenesis have recently been implicated in cerebral ischemia, the positive effect of stimulating ETB receptors in cerebral ischemia may be mediated through mitochondrial functions.