Udenafil decreases portal pressure and improves erectile dysfunction in liver cirrhosis

Uschner, Frank Erhard; Glückert, Kathleen; Klein, Sabine; Magdaleno, Fernando; Schierwagen, Robert; Trebicka, Jonel

doi:10.1016/s0168-8278(18)31189-9

Cited by 2 publications

(2 citation statements)

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“…The portal pressure decreased by approximately 20%, while MAP was lowered by only 5% [34]. Recently, these findings were supported by Trebicka et al [78,79]. The effect of PDE-5-Is on MAP was much less than its effects on portal pressure.…”

Section: Discussionmentioning

confidence: 65%

Close Relationship between Systemic Arterial and Portal Venous Pressure in an Animal Model with Healthy Liver

Lazaro

Stoll²,

Elverfeldt

et al. 2023

IJMS

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It is unclear to what extent systemic arterial blood pressure influences portal pressure. This relationship is clinically important as drugs, which are conventionally used for therapy of portal hypertension, may also influence systemic arterial blood pressure. This study investigated the potential correlation between mean arterial (MAP) and portal venous pressure (PVP) in rats with healthy livers. In a rat model with healthy livers, we investigated the effect of manipulation of MAP on PVP. Interventions consisted of 0.9% NaCl (group 1), 0.1 mg/kg body weight (bw) Sildenafil (low dose), an inhibitor of phosphodiesterase-5 (group 2), and 1.0 mg/kg bw Sildenafil (high dose, group 3) in 600 µL saline injected intravenously. Norepinephrine was used to increase MAP in animals with circulatory failure while PVP was monitored. Injection of the fluids induced a transient drop in MAP and PVP, probably due to a reversible cardiac decompensation. The drop in MAP and drop in PVP are significantly correlated. The time lag between change in MAP and change in PVP by 24 s in all groups suggests a cause-and-effect relationship. Ten minutes after the injection of the fluid, cardiac function was normalized. Thereafter, MAP gradually decreased. In the NaCl group, PVP decreases by 0.485% for a 1% drop of MAP, by 0.550% in the low-dose sildenafil group, and by 0.651% in the high-dose sildenafil group (p < 0.05 for difference group two vs. group one, group three vs. group one, and group three vs. group two). These data suggest that Sildenafil has an inherent effect on portal pressure that exceeds the effect of MAP. Injection of norepinephrine led to a sudden increase in MAP followed by an increase in PVP after a time lag. These data show a close relationship between portal venous pressure and systemic arterial pressure in this animal model with healthy livers. A change in MAP is consequently followed by a change in PVP after a distinct time lag. This study, furthermore, suggests that Sildenafil influences portal pressure. Further studies should be performed in a model with cirrhotic livers, as these may be important in the evaluation of vasoactive drugs (e.g., PDE-5-inhibitors) for therapy of portal hypertension.

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Section: Discussionmentioning

confidence: 65%

Close Relationship between Systemic Arterial and Portal Venous Pressure in an Animal Model with Healthy Liver

Lazaro

Stoll²,

Elverfeldt

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Heart rate (HR) remained unaltered regardless of the applied dosage. Uschner et al confirmed the effect of udenafil on PVP in the BDL- and CCl 4 -model of liver cirrhosis [ 97 , 156 ]. Their most recent study moreover investigated the acute effects of a combination of udenafil with the NSBB propranolol [ 97 ].…”

Section: Targeting Components Of the No-cgmp Pathway For Therapy Omentioning

confidence: 98%

Phosphodiesterases in the Liver as Potential Therapeutic Targets of Cirrhotic Portal Hypertension

Kreisel

Schaffner

Lazaro

et al. 2020

IJMS

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Liver cirrhosis is a frequent condition with high impact on patients’ life expectancy and health care systems. Cirrhotic portal hypertension (PH) gradually develops with deteriorating liver function and can lead to life-threatening complications. Other than an increase in intrahepatic flow resistance due to morphological remodeling of the organ, a functional dysregulation of the sinusoids, the smallest functional units of liver vasculature, plays a pivotal role. Vascular tone is primarily regulated by the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, wherein soluble guanylate cyclase (sGC) and phosphodiesterase-5 (PDE-5) are key enzymes. Recent data showed characteristic alterations in the expression of these regulatory enzymes or metabolite levels in liver cirrhosis. Additionally, a disturbed zonation of the components of this pathway along the sinusoids was detected. This review describes current knowledge of the pathophysiology of PH with focus on the enzymes regulating cGMP availability, i.e., sGC and PDE-5. The results have primarily been obtained in animal models of liver cirrhosis. However, clinical and histochemical data suggest that the new biochemical model we propose can be applied to human liver cirrhosis. The role of PDE-5 as potential target for medical therapy of PH is discussed.

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Udenafil decreases portal pressure and improves erectile dysfunction in liver cirrhosis

Cited by 2 publications

References 0 publications

Close Relationship between Systemic Arterial and Portal Venous Pressure in an Animal Model with Healthy Liver

Close Relationship between Systemic Arterial and Portal Venous Pressure in an Animal Model with Healthy Liver

Phosphodiesterases in the Liver as Potential Therapeutic Targets of Cirrhotic Portal Hypertension

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