scholarly journals Cerebral Haemodynamic Response or Excitability is not Affected by Sildenafil

2009 ◽  
Vol 29 (4) ◽  
pp. 830-839 ◽  
Author(s):  
Christina Kruuse ◽  
Adam E Hansen ◽  
Henrik BW Larsson ◽  
Martin Lauritzen ◽  
Egill Rostrup
Keyword(s):  
Neuronal Excitability ◽  
Visual Stimulation ◽  
Cerebral Arteries ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Visual Response ◽  
Fmri Response ◽  
Phosphodiesterase 5 ◽  
Hypercapnic Response ◽  
Healthy Females

Sildenafil (Viagra®), a cyclic guanosine monophosphate-degrading phosphodiesterase 5 inhibitor, induces headache and migraine. Such headache induction may be caused by an increased neuronal excitability, as no concurrent effect on cerebral arteries is found. In 13 healthy females (23±3 years, 70.3±6.6 kg), the effect of sildenafil on a visual (reversing checkerboard) and a hypercapnic (6% CO2 inhalation) response was evaluated using functional magnetic resonance imaging (fMRI, 3 T MR scanner). On separate occasions, visual-evoked potential (VEP) measurements (latency (P100) and maximal amplitude) were performed. The measurements were applied at baseline and at both 1 and 2 h after ingestion of 100mg of sildenafil. Blood pressure, heart rate and side effects, including headache, were obtained. Headache was induced in all but one subject on both study days. Sildenafil did not affect VEP amplitude or latency (P100). The fMRI response to visual stimulation or hypercapnia was unchanged by sildenafil. In conclusion, sildenafil induces mild headache without potentiating a neuronal or local cerebrovascular visual response or a global cerebrovascular hypercapnic response. The implication is that sildenafil-induced headache does not include a general lowering of threshold for a neuronal or cerebrovascular response, and that sildenafil does not modulate the hypercapnic response in healthy subjects.

scholarly journals Hemolysate Inhibits Cerebral Artery Relaxation

1988 ◽  
Vol 8 (1) ◽  
pp. 46-53 ◽  
Author(s):  
Noboru Toda
Keyword(s):  
Methylene Blue ◽  
Angiotensin Ii ◽  
Substance P ◽  
Cerebral Arteries ◽  
Vascular Wall ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Middle Cerebral Arteries ◽  
Relaxant Response ◽  
Stimulation Of

In helical strips of dog middle cerebral arteries partially contracted with prostaglandin (PG) F2α, relaxations induced by angiotensin-II, possibly mediated by PGI2, and those induced by PGH2 were reversed to a contraction or markedly reduced by treatment with hemolysate, which, however, attenuated the PGI2-induced relaxation only slightly. The relaxant response of human middle cerebral arterial strips to PGH2 was also suppressed by hemolysate. Dog and monkey middle cerebral arteries responded to transmural electrical stimulation and nicotine with transient relaxations, which were quite susceptible to tetrodotoxin and hexamethonium, respectively; the relaxations were abolished almost completely by hemolysate and methylene blue. On the other hand, the relaxant response of dog cerebral arteries to a low concentration of K+ was not influenced by hemolysate or by methylene blue, but was reversed to a contraction by treatment with ouabain. Relaxations induced by substance-P and nitroglycerin were markedly inhibited by hemolysate; removal of endothelium abolished the relaxation by substance-P, but did not influence the nitroglycerin-induced relaxation. Hemolysate may interfere with the biosynthesis of PGI2 in the vascular wall, thereby reversing the relaxation induced by angiotensin-II and PGH2 to a contraction. Relaxations induced by electrical and chemical stimulation of vasodilator nerves innervating cerebral arteries appear to be elicited by a mechanism dependent on cellular cyclic guanosine monophosphate (GMP), like that underlying the substance-P-induced and nitroglycerin-induced relaxation. These actions of hemolysate may be involved in the genesis of cerebral vasospasm after subarachnoid hemorrhage.

Cyclic guanosine monophosphate phosphodiesterase-5 inhibitor promotes an endothelium NO-dependent-like vasodilation in patients with refractory hypertension

Nitric Oxide ◽  
2007 ◽  
Vol 16 (3) ◽  
pp. 315-321 ◽  
Author(s):  
Juan Carlos Yugar-Toledo ◽  
Sílvia E. Ferreira-Melo ◽  
Fernanda M. Consolim-Colombo ◽  
Maria C. Irigoyen ◽  
Otávio Rizzi Coelho ◽  
...  
Keyword(s):  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Refractory Hypertension ◽  
Phosphodiesterase 5 Inhibitor ◽  
Cyclic Guanosine Monophosphate Phosphodiesterase ◽  
Phosphodiesterase 5

Cyclic guanosine monophosphate modulates accumulation of phosphodiesterase 5 inhibitors in human platelets

2017 ◽  
Vol 145 ◽  
pp. 54-63 ◽  
Author(s):  
Gzona Bajraktari ◽  
Jürgen Burhenne ◽  
Peter Bugert ◽  
Walter Emil Haefeli ◽  
Johanna Weiss
Keyword(s):  
Cyclic Guanosine Monophosphate ◽  
Human Platelets ◽  
Guanosine Monophosphate ◽  
Phosphodiesterase 5 Inhibitors ◽  
Phosphodiesterase 5

scholarly journals Endothelium-Dependent Dilation of Feline Cerebral Arteries: Role of Membrane Potential and Cyclic Nucleotides

1989 ◽  
Vol 9 (3) ◽  
pp. 256-263 ◽  
Author(s):  
Joseph E. Brayden ◽  
George C. Wellman
Keyword(s):  
Membrane Potential ◽  
Cyclic Nucleotides ◽  
Cerebral Arteries ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Membrane Potential Change ◽  
Middle Cerebral Arteries

The objective of this study was to characterize the role of membrane potential and cyclic nucleotides in endothelium-dependent dilation of cerebral arteries. Middle cerebral arteries isolated from cats were depolarized and constricted in response to serotonin or when subjected to transmural pressures >50 mm Hg. Acetylcholine (ACh) and ADP caused vasodilation and a sustained, dose-dependent hyperpolarization of up to 20 mV in this artery. The membrane potential change preceded the vasodilation by ∼6 s. Hyperpolarizations and dilations to ACh and ADP did not occur in preparations without endothelium. The hyperpolarizations were abolished by ouabain (10−5 M), which also blocked the dilator response to ACh. However, dilations to ADP were unaffected by ouabain. Methylene blue (5 × 10−5 M), a guanylate cyclase inhibitor, had no effect on the responses to ACh or ADP in the presence or absence of ouabain. Cyclic guanosine monophosphate (cGMP) levels were not altered in cerebral arteries exposed to ACh or ADP. However, ADP did increase cyclic adenosine monophosphate levels in these blood vessels. We conclude that although membrane hyperpolarizations may be adequate to cause vasodilation, at least one other pathway of endothelium-dependent vasodilation also is present in feline cerebral arteries. Cyclic GMP does not appear to be involved in this alternate pathway of dilation.

scholarly journals Activation of the PI3-K/Akt Pathway Mediates cGMP Enhanced-Neurogenesis in the Adult Progenitor Cells Derived from the Subventricular Zone

2005 ◽  
Vol 25 (9) ◽  
pp. 1150-1158 ◽  
Author(s):  
Lei Wang ◽  
Zheng Gang Zhang ◽  
Rui Lan Zhang ◽  
Michael Chopp
Keyword(s):  
Subventricular Zone ◽  
Glycogen Synthase ◽  
Specific Inhibitor ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Glycogen Synthase Kinase 3 ◽  
Downstream Target ◽  
Adult Rat ◽  
Phosphorylated Akt ◽  
Phosphodiesterase 5

The intracellular mechanisms that regulate neurogenesis remain unclear. Using neurospheres isolated from the subventricular zone (SVZ) of the adult rat, we investigated the effect of cyclic guanosine monophosphate (cGMP) and its signaling pathway on the induction of neurogenesis. Neurospheres expressed phosphodiesterase 5 (PDE5) and treatment of neurospheres with Sildenafil, a specific inhibitor of PDE5, significantly increased cGMP levels and neurogenesis. In addition, incubation of neurospheres with Sildenafil significantly phosphorylated Akt, which was associated with an increase of phosphorylation of glycogen synthase kinase 3 (GSK-3), a downstream target of Akt. Coincubation of neurospheres with Sildenafil and LY 294002, a pharmacological inhibitor of PI3-K/Akt, abolished Sildenafil-induced phosphorylated Akt and GSK-3. Furthermore, LY 294002 blocked Sildenafil-increased SVZ cell proliferation. These data suggest that Sildenafil-enhanced neurogenesis likely occurs through activation of the PI3-K/Akt/GSK-3 pathway.

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