Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although sildenafil (Viagra) and other phosphodiesterase V (PDE V) inhibitors are increasingly recognized for their use in the treatment of male erectile dysfunction and perhaps more recently pulmonary artery hypertension, less is known of their potential beneficial effects in other situations. Medeiros et al., in the current issue of the British Journal of Pharmacology, report that sildenafil dramatically reduces alcohol-induced gastric damage in rats. The authors provide convincing evidence that such protection not only occurs via the nitric oxide (NO)/cGMP pathway, but also involves regulation of ATP-sensitive potassium channels. Therefore, in addition to exerting anti-impotence efficacy, PDE V inhibitors may provide significant beneficial effects from mucosal injury induced by alcohol.
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PMID:Sildenafil reduces alcohol-induced gastric damage: just say 'NO'. 1807

Sildenafil citrate (Revatio), an inhibitor of phosphodiesterase type 5 (PDE5), is approved for use in the US, Europe and other countries for the treatment of pulmonary arterial hypertension (PAH). Oral sildenafil 20 mg three times daily added to conventional background therapy was significantly more effective than placebo at increasing exercise capacity in patients with idiopathic PAH or PAH associated with connective tissue diseases or repaired congenital systemic-to-pulmonary shunts. Sildenafil was also associated with improvements in WHO functional class and haemodynamic parameters, and was generally well tolerated. Sildenafil provides benefits in terms of exercise capacity when added to epoprostenol; however, these findings come from a trial that did not use the approved dosage of sildenafil. In conclusion, sildenafil is an effective oral treatment option for patients with PAH.
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PMID:Sildenafil: a review of its use in pulmonary arterial hypertension. 1825 13

Phosphodiesterase (PDE) isoenzymes hold a central role in controlling levels of the cyclic nucleotide monophosphates cyclic AMP and cyclic GMP, which are important second messengers in many transmitter pathways involved in regulating biological processes in urogenital tissues. The development of the PDE5 inhibitors Sildenafil (Viagra), Vardenafil (Levitra), and Tadalafil (Cialis), combining a high response rate and the advantage of on-demand intake, is the result of the scientific characterization of the physiology of penile erectile smooth muscle.The introduction of these compounds as safe and well-tolerated orally active drugs for the treatment of erectile dysfunction has not only become a worldwide clinical success, but it provided the basis for the development and introduction of several new therapeutic modalities into the management of male and female sexual dysfunction. It has also brought further attention to cyclic nucleotide phosphodiesterases as putative pharmacological targets in a variety of disorders, such as pulmonary arterial hypertension, Raynaud's disease, Peyronie's disease, the so-called benign prostatic syndrome, endothelial dysfunction, disturbances of male ejaculatory function (premature ejaculation), and female sexual dysfunction.Because the concept of taking a pill to cure an illness or relieve disease symptoms has become widely accepted by consumers, pharmacological research and development is focusing primarily on selective orally available drugs that influence peripheral intracellular or central regulatory mechanisms. This review briefly describes the current and evolving advances in the field of PDE5 pharmacotherapy in urology and other fields of medicine.
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PMID:[The basics of phosphodiesterase type 5 (PDE5) inhibition in urology]. 1885 69

Sildenafil (Viagra) has been developed as a drug to treat male impotence. It has also been used to reduce symptoms (e.g. improved exercise capacity) in patients with pulmonary arterial hypertension. A case of subarachnoid haemorrhage (SAH) following the illicit use of sildenafil is reported.
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PMID:Subarachnoid haemorrhage: possibly caused by the illegitimate use of sildenafil citrate. 1926 10

A case of cerebral hemorrhage associated with sildenafil (Revatio) use in an infant is presented. Sildenafil is increasingly used in the treatment of primary and secondary pulmonary arterial hypertension and pulmonary arteriovenous fistula. In the reported case, sildenafil used to treat pulmonary arteriovenous fistula improved right-to-left shunting across the pulmonary fistula but resulted in cerebral hemorrhage. Cerebral hemorrhage, a previously reported complication of sildenafil, developed in an infant after a rapid increase in dose, to 4.7 mg/kg/day. Therefore, sildenafil doses must be increased only with care, and cerebral hemorrhage must be considered a potential complication.
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PMID:Cerebral hemorrhage associated with sildenafil (Revatio) in an infant. 1958

Pulmonary arterial hypertension is a disease characterized by progressive obliteration of the pulmonary vasculature leading to right-ventricular failure and if untreated, death. Several effective therapies are now available for pulmonary arterial hypertension. These therapies target specific abnormalities in the endothelium, including prostacyclin and nitric oxide deficiencies, and endothelin excess. Sildenafil, a phosphodiesterase type-5 inhibitor, has garnered interest recently for the treatment of pulmonary arterial hypertension because it increases cyclic GMP--a second messenger in the nitric oxide pathway. Early studies suggested a favorable response with traditional measures of a 6-min walk and hemodynamics in pulmonary arterial hypertension patients. Recently, sildenafil was approved by the US Food and Drug Administration and the European Medicines Agency under the trade name Revatio (Pfizer, Inc.). Sildenafil is well tolerated and adverse events have been shown to be mild and transient. Potential benefits of sildenafil therapy include its ease of administration and safety profile.
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PMID:Sildenafil for pulmonary arterial hypertension. 1980 69

PDE5 inhibitors have been clearly established as first-line therapy for the treatment of erectile dysfunction (ED). Three PDE5 inhibitors--sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis)--are currently approved by the FDA and the EMEA for use in ED, whereas sildenafil is also marketed under a different proprietary name (Revatio) for the treatment of pulmonary arterial hypertension (PAH). A forth PDE5 inhibitor, udenafil (Zydena), is currently marketed. In the present review the molecular basis and the mechanism of action of PDE5 inhibitors is discussed. In addition experimental and clinical data concerning their effects on different tissues, organs and systems is systematically reviewed and their possible beneficial action in numerous disorders is presented.
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PMID:PDE5 inhibitors: in vitro and in vivo pharmacological profile. 1986 Jun 92

Sildenafil citrate (Viagra), a cGMP-selective phosphodiesterase (PDE) inhibitor, is widely used to treat erectile dysfunction and pulmonary arterial hypertension. In contrast to its well established action on erectile dysfunction, little is known on the action of sildenafil on cGMP/cAMP signaling and testicular steroidogenesis. This study was designed to assess the effects of prolonged sildenafil treatment on NO synthase-dependent signaling and steroidogenic function of rat Leydig cells. Male adult rats were treated with Viagra (1.25 mg/kg body wt) daily for 30 days. In our studies, serum testosterone and ex vivo testosterone production significantly increased in sildenafil-treated animals. Human chorionic gonadotropin-stimulated testosterone production and cAMP accumulation were also significantly higher in Leydig cells obtained from sildenafil-treated rats. The expression of soluble guanylyl cyclase (GUCY1) subunits (Gucy1a1, Gucy1b1) significantly increased; cAMP-specific Pde4a, cGMP-specific Pde6c, and dual Pde1c and Nos2 were inhibited and expression of Nos3, protein kinase G1 (Pkg1), and Pde5 remained unchanged. Treatment of purified Leydig cells with NO donor caused a dose-dependent increase in both testosterone and cGMP production. Testosterone and cGMP production was significantly higher in Leydig cells obtained from sildenafil-treated animals. The stimulatory effect of NO donor was significantly enhanced by saturating concentrations of hCG in both Leydig cells obtained from control and sildenafil-treated animals. Occurrence of mature steroidogenic acute regulatory protein also increased in sildenafil treated animals in accord with increased cAMP and cGMP production. In summary, inhibition of PDE activity during prolonged sildenafil treatment increased serum testosterone level and Leydig cells' steroidogenic capacity by coordinated stimulatory action on cAMP and cGMP signaling pathway.
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PMID:Sildenafil treatment in vivo stimulates Leydig cell steroidogenesis via the cAMP/cGMP signaling pathway. 2066 85

We present a patient with an acute cervical spinal cord infarction resulting from the use of sildenafil (Viagra) in combination with his hypertension medication. Symptoms were acute and rapidly progressive, and MR imaging with DWI was crucial in confirming the diagnosis.
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PMID:Sildenafil-induced cervical spinal cord infarction. 2190 16

Preeclampsia and fetal growth restriction are responsible for the majority of maternal and perinatal morbidity and mortality associated with complicated pregnancies. Although their etiologies are complex and multifactorial, both are associated with increased uterine artery resistance. Sildenafil citrate is able to rescue the dysfunction observed ex vivo in uterine arteries of women with preeclampsia. The ability of sildenafil citrate to increase uterine artery vasodilation, thereby decreasing uterine artery resistance and, hence, ameliorated preeclampsia and fetal growth restriction, was tested in a mouse model of preeclampsia, the catechol-O-methyl transferase knockout mouse (COMT(-/-)). COMT(-/-) and C57BL/6J mice were treated (0.2 mg/mL in drinking water, n=6-12) from gestational day 12.5 to 18.5. Measures of pup growth, including body weight, crown/rump length, and abdominal circumference, were reduced in COMT(-/-) mice; this was normalized after treatment with Sildenafil. COMT(-/-) mice also demonstrated abnormal umbilical Doppler waveforms, including reverse arterial blood flow velocity. This was normalized after treatment with Sildenafil. Abnormal uterine artery Doppler waveforms were not demonstrated in COMT(-/-) mice, although ex vivo responses of uterine arteries to phenylephrine were increased; moreover, treatment with Sildenafil did improve ex vivo sensitivity to an endothelium-dependent vasodilator. The data presented here demonstrate that Sildenafil can rescue pup growth and improve abnormal umbilical Doppler waveforms, providing support for a potential new therapeutic strategy targeting fetal growth restriction.
Hypertension 2012 May
PMID:Sildenafil citrate rescues fetal growth in the catechol-O-methyl transferase knockout mouse model. 2239 99


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