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

Abstract TP475: Effect of Udenafil, a Phosphodiesterase-5 Inhibitor, on Angiogenesis in a Cav-1 Deficient Moyamoya Disease Model

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Hyung Jun Kim ◽  
Oh Young Bang ◽  
In-Young Baek ◽  
Jae-Hwan Kim ◽  
Ye Sel Kim ◽  
...  
Keyword(s):  
Moyamoya Disease ◽  
Growth Factor Receptor ◽  
Guanosine Monophosphate ◽  
Therapeutic Effects ◽  
Mural Cell ◽  
Phosphodiesterase 5 Inhibitor ◽  
Vessel Maturation ◽  
Phosphodiesterase 5

Background: Although pathogenic mechanisms of moyamoya disease remain unknown, recent studies suggest that it is a caveolae disease. This study evaluated the effect of udenafil, a phosphodiesterase-5 inhibitor, on vessel maturation in in vitro and in vivo moyamoya disease models. Methods: Angiogenesis and vessel maturation were assessed in in vitro models, caveolin-1 (Cav-1) knockdown human umbilical vessel endothelial cells (HUVECs) and coronary artery smooth muscle cells (CASMCs), and in in vivo model of bilateral internal carotid artery occlusion (bICAo). Udenafil was administered (1,3,10 and 30 μM) in cell culture conditions, and functional studies (migration and tube formation assay) were performed and vessel maturation factors and cyclic guanosine monophosphate (cGMP) accumulation were measured. Udenafil (3 and 10 mg/kg) was orally administered once daily for 4 weeks in bICAo rat model, and histological analysis for angiogenesis and vessel maturation was performed. Results: Udenafil increased vessel formation in both Cav-1 knockdown HUVEC and bICAo models without increased migration/proliferation of HUVECs and CASMCs. Udenafil increased CD31+ vessel density and NG2/Col4+ mural cell density in bICAo models. Cav-1 knockdown inhibited accumulation of cGMP, and udenafil treatment restored cGMP levels in Cav-1 knockdown HUVEC models. Vessel maturation factors (angiopoietin-1 and platelet-derived growth factor receptor-β) and angiogenic factors (endothelial nitric oxide synthase) were increased after treatment with udenafil in vitro . Conclusion: Our results indicate that udenafil reversed cellular levels of cGMP related to Cav-1 deficiency and induced angiogenesis and vessel maturation. Further studies are warranted to confirm the therapeutic effects of this strategy in moyamoya disease.

Dibenzoquinazoline diones as antihypertensive cyclic guanosine monophosphate phosphodiesterase inhibitors

1987 ◽  
Vol 36 (20) ◽  
pp. 3517-3521 ◽  
Author(s):  
Robert F.G. Booth ◽  
Susan P. Buckham ◽  
David O. Lunt ◽  
Paul W. Manley ◽  
Roderick A. Porter
Keyword(s):  
Phosphodiesterase Inhibitors ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Cyclic Guanosine Monophosphate Phosphodiesterase

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.

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