Cerebral Blood Flow Regulation by Nitric Oxide: Recent Advances

Toda, Noboru; Ayajiki, Kazuhide; Okamura, Tomio

doi:10.1124/pr.108.000547

Cited by 324 publications

(263 citation statements)

References 415 publications

(365 reference statements)

Supporting

Mentioning

248

Contrasting

Unclassified

Order By: Relevance

“…A recent study showed that baicalin pretreatment reduced the hyperthermia, intracranial hypertension, and increase of nitric oxide metabolite levels during heatstroke; baicalin also suppressed the heatstroke-induced increase in IL-1β and TNF-α levels [12]. Baicalin may thus protect against cerebrovascular dysfunction and brain inflammation in heatstroke [13]. Although baicalin has been also found to induce apoptosis and to inhibit inflammation through multiple pathways, little is known about the role of baicalin in regulating VSMC proliferation and prevention of restenosis.…”

Section: Introductionmentioning

confidence: 99%

Baicalin inhibits PDGF-BB-stimulated vascular smooth muscle cell proliferation through suppressing PDGFRβ-ERK signaling and increase in p27 accumulation and prevents injury-induced neointimal hyperplasia

et al. 2010

View full text Add to dashboard Cite

The increased proliferation and migration of vascular smooth muscle cells (VSMCs) are key events in the development of atherosclerotic lesions. Baicalin, an herb-derived flavonoid compound, has been previously shown to induce apoptosis and growth inhibition in cancer cells through multiple pathways. However, the potential role of baicalin in regulation of VSMC proliferation and prevention of cardiovascular diseases remains unexplored. In this study, we show that pretreatment with baicalin has a dose-dependent inhibitory effect on PDGF-BB-stimulated VSMC proliferation, accompanied with the reduction of proliferating cell nuclear antigen (PCNA) expression. We also show that baicalin-induced growth inhibition is associated with a decrease in cyclin E-CDK2 activation and increase in p27 level in PDGF-stimulated VSMCs, which appears to be at least partly mediated by blockade of PDGF receptor β (PDGFRβ)-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. In addition, baicalin was also found to inhibit adhesion molecule expression and cell migration induced by PDGF-BB in VSMCs. Furthermore, using an animal carotid arterial balloon-injury model, we found that baicalin significantly inhibited neointimal hyperplasia. Taken together, our results reveal a novel function of baicalin in inducing growth arrest of PDGF-stimulated VSMCs and suppressing neointimal hyperplasia after balloon injury, and suggest that the underlying mechanism involves the inhibition of cyclin E-CDK2 activation and the increase in p27 accumulation via blockade of the PDGFRβ-ERK1/2 signaling cascade.

show abstract

Section: Introductionmentioning

confidence: 99%

Baicalin inhibits PDGF-BB-stimulated vascular smooth muscle cell proliferation through suppressing PDGFRβ-ERK signaling and increase in p27 accumulation and prevents injury-induced neointimal hyperplasia

et al. 2010

View full text Add to dashboard Cite

show abstract

“…1,2 Histochemistry has showed that nitric oxide synthase (NOS)-containing nerves originating from the pterygoparatine ganglion (PPG) innervate arteries irrigating the cerebrum in many species. [3][4][5][6] We have reported that electrical stimulation of the unilateral PPG or the greater petrosal nerve (GPN), a preganglionic parasympathetic nerve that synaptically connects to the PPG, dilates the ipsilateral anterior cerebral artery (ACA), and the middle cerebral artery (MCA) in anesthetized monkeys 7 and dogs. 8 We have also found that these dilatations are suppressed by a NOS inhibitor.…”

Section: Introductionmentioning

confidence: 99%

Nitrergic nerves derived from the pterygopalatine ganglion innervate arteries irrigating the cerebrum but not the cerebellum and brain stem in monkeys

et al. 2011

Self Cite

View full text Add to dashboard Cite

The functional roles of the nitrergic nerves innervating the monkey cerebral artery were evaluated in a tension-response study examining isolated arteries in vitro and cerebral angiography in vivo. Nicotine produced relaxation of arteries by stimulation of nerve terminals innervating isolated monkey arteries irrigating the cerebrum, cerebellum and brain stem. Relaxation of arteries induced by nicotine was abolished by treatment with N G -nitro-L-arginine, a nitric oxide synthase inhibitor, and was restored by addition of L-arginine. Cerebral angiography showed that electrical stimulation of the unilateral greater petrosal nerve, which connects to the pterygopalatine ganglion via the parasympathetic ganglion synapse, produced vasodilatation of the anterior, middle and posterior cerebral arteries in the stimulated side. However, stimulation failed to produce vasodilatation of the superior and anterior-inferior cerebellar arteries and the basilar artery in anesthetized monkeys. Therefore, nitrergic nerves derived from the pterygopalatine ganglion appear to regulate cerebral vasomotor function. In contrast, circulation in the cerebellum and brain stem might be regulated by nitrergic nerves originating not from the pterygopalatine ganglion, but rather from an unknown ganglion (or ganglia).

show abstract

“…11 Reduced availability of NO in blood and cerebrospinal fluid is one of the important mechanisms underlying cerebral Hemoglobin released following aneurysmal rupture inhibits NO production of endothelial nitric oxide synthase and decreases NO availability for smooth muscle cells, leading to vasoconstriction. [11][12][13] Successful delivery of NO to the cerebral arteries may help prevent the genesis of cerebral vasospasm and provide cerebral vascular relaxation in patients with subarachnoid hemorrhage. 14 Ultrasound contrast agents usually contain a perfluorcarbon gas stabilized by a shell of biocompatible material such as protein, 15 lipid, [16][17][18][19] or polymer.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage

Kim¹,

Britton²,

Peng³

et al. 2013

IJN

View full text Add to dashboard Cite

Delayed cerebral vasospasm following subarachnoid hemorrhage causes severe ischemic neurologic deficits leading to permanent neurologic dysfunction or death. Reduced intravascular and perivascular nitric oxide (NO) availability is a primary pathophysiology of cerebral vasospasm. In this study, we evaluated NO-loaded echogenic liposomes (NO-ELIP) for ultrasound-facilitated NO delivery to produce vasodilation for treatment of vasospasm following subarachnoid hemorrhage. We investigated the vasodilative effects of NO released from NO-ELIP both ex vivo and in vivo. Liposomes containing phospholipids and cholesterol were prepared, and NO was encapsulated. The encapsulation and release of NO from NO-ELIP were determined by the syringe/vacuum method and ultrasound imaging. The ex vivo vasodilative effect of NO-ELIP was investigated using rabbit carotid arteries. Arterial vasodilation was clearly observed with NO-ELIP exposed to Doppler ultrasound whereas there was little vasodilative effect without exposure to Doppler ultrasound in the presence of red blood cells. Penetration of NO into the arterial wall was determined by fluorescent microscopy. The vasodilative effects of intravenously administered NO-ELIP in vivo were determined in a rat subarachnoid hemorrhage model. NO-ELIP with ultrasound activation over the carotid artery demonstrated effective arterial vasodilation in vivo resulting in improved neurologic function. This novel methodology for ultrasound-controlled delivery of NO has the potential for therapeutic treatment of vasospasm following subarachnoid hemorrhage. This ultrasound-controlled release strategy provides a new avenue for targeted bioactive gas and therapeutic delivery for improved stroke treatment.

show abstract

Cerebral Blood Flow Regulation by Nitric Oxide: Recent Advances

Cited by 324 publications

References 415 publications

Baicalin inhibits PDGF-BB-stimulated vascular smooth muscle cell proliferation through suppressing PDGFRβ-ERK signaling and increase in p27 accumulation and prevents injury-induced neointimal hyperplasia

Baicalin inhibits PDGF-BB-stimulated vascular smooth muscle cell proliferation through suppressing PDGFRβ-ERK signaling and increase in p27 accumulation and prevents injury-induced neointimal hyperplasia

Nitrergic nerves derived from the pterygopalatine ganglion innervate arteries irrigating the cerebrum but not the cerebellum and brain stem in monkeys

Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage

Contact Info

Product

Resources

About