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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary Arterial Hypertension includes a heterogeneous group of disorders with a common genetic, pathological and hemodinamyc origin. It is characterized by a high pulmonary artery pressure due to a primary vascular disease, as a consequence of genetic and environmental factors. The common pathway is a vascular imbalance towards vasoconstriction and proliferation inside the small vessels. According to the World Health Organization, 2003, Pulmonary Arterial Hypertension is classified as idiopathic, familiar or associated to connective tissue diseases, HIV, drugs, porto-pulmonary hypertension, congenital intracardiac shunts and others. The diagnosis is based in hemodynamics. Echocardiogram is a non invasive and right ventricular catheterization is an invasive diagnostic tool. Follow up is based on a clinical and functional assessment through functional class classification, dyspnea scores and 6-minute walking test. The prognosis is historically devastating but new therapies are changing the natural history of the disease. New treatments have demonstrated improvement in symptoms, hemodynamic profiles and survival. Intravenous, subcutaneous or inhaled prostanoids such as Epoprostenol, Treprostinil or Iloprost respectively have been approved for Pulmonary Arterial Hypertension treatment as well as oral endothelial receptor blockers. They are all considered first line treatments for arterial pulmonary hypertensive patients with even better benefits than lung transplantation. Phosphodiesterase inhibitors (Sildenafil), have been recently approved for the treatment of pulmonary arterial hypertension.
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PMID:[Update in the diagnosis and therapy for pulmonary arterial hypertension]. 1713 Sep 75

Phosphodiesterase-5 inhibitors (PDE5I) are an important new class of drugs in the treatment of pulmonary artery hypertension (PHT). Sildenafil, a selective PDE5I, through its action on the NO/cGMP signal pathway, causes a selective reduction of pulmonary vascular resistance and improves symptoms and exercise capacity of patients with PHT. The phase III trial (SUPER-1) has clearly shown the efficacy and safety of sildenafil in PHT so that its use for this indication has recently been approved. Current guidelines of several large specialist societies have included sildenafil for the treatment of PHT, supported by a high degree of evidence. Sildenafil can also be combined with other drugs and has the potential of being efficacious also in other forms of pulmonary hypertension.
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PMID:[Treatment of pulmonary arterial hypertension: phosphodiesterase-5 inhibitors]. 1713 94

Recent analyses suggest that about 67-68% of men with hypertension have some degree of erectile dysfunction (ED). With about 25 million men in the US with hypertension, substantial numbers of hypertension-related ED exist that tend to be of a more severe nature than the general population. Men with ED are also more likely to have hypertension. Thiazide diuretic and beta-blocker therapy may contribute to ED. Phosphodiesterase-5 (PDE5) inhibitors are effective therapy in men with ED owing to hypertension who are taking antihypertensive medicines including those on multiple antihypertensive medicines. The addition of PDE5 inhibitors to usual common antihypertensive medicines (diuretics, beta blockers, calcium blockers, angiotensin converting enzyme inhibitors and angiotensin receptor blockers) results in either no or small additive reductions in blood pressure (BP) and no increase in serious clinical adverse events. There are however precautions regarding the use of PDE5 inhibitors in patients taking alpha blockers for either hypertension or benign prostatic hypertrophy, as some patients may develop orthostatic hypotension. Organic nitrates remain an absolute contraindication for PDE5 inhibitors because synergistic and symptomatic reductions in BP may occur in some patients with this drug combination.
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PMID:Erectile dysfunction and hypertension. 1715 96

Phosphodiesterase inhibitors like sildenafil have already been shown to improve functional capacity and hemodynamics in the treatment of pulmonary arterial hypertension. Few studies address the effects of new phosphodiesterase inhibitors as tadalafil. We report a case of a patient with idiopathic pulmonary arterial hypertension in functional class IV (New York Heart Association) with significant response to treatment with tadalafil.
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PMID:Tadalafil as treatment for idiopathic pulmonary arterial hypertension. 1739 93

Erectile dysfunction (ED) is a common condition with a significant effect on quality of life. The prevalence of ED increases with age and other risk factors (hypertension, diabetes, smoking, coronary heart disease, dyslipidemia and depression). Nitric oxide (NO) activity is adversely affected, in penile and vascular tissue, by these risk factors. Endothelial dysfunction and a reduced generation or bioavailability of NO have emerged as major pathophysiological mechanisms in ED. Hyperlipidemia may impair erectile function by affecting endothelial and smooth muscle cells of the penis. Oxidized low-density lipoprotein is a causative factor for the impaired relaxation response of the corpus cavernosum. Elevated serum cholesterol and reduced high density lipoprotein cholesterol levels are associated with an increased risk of ED. It follows that treating dyslipidemia could have a beneficial effect on ED. Phosphodiesterase type 5 inhibitors are now considered as first line treatment for ED. There is evidence that statins improve responses to these drugs. ED is considered as a warning sign of silent or early vascular disease. The use of statins may be beneficial in these patients.
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PMID:Dyslipidemia as a risk factor for erectile dysfunction. 1762 14

Recent experimental evidence suggests that arterial insufficiency precedes the structural and functional changes in corpora cavernosa (CC) leading to organic erectile dysfunction (ED). The present review gives an overview of the physiological factors involved in the regulation of penile vasculature. Sympathetic nerves maintain flaccidity and tonically released noradrenaline induces vasoconstriction of both arteries and veins through alpha(1)- and alpha(2)-postsynaptic receptors and downregulates its own release and that of nitric oxide (NO) through alpha(2)-presynaptic receptors. The sympathetic cotransmitter neuropeptide Y (NPY) modulates noradrenergic vasoconstriction in penile small arteries by both enhancing and depressing noradrenaline contractions through Y(1)- and Y(2)-postsynaptic and a NO-independent atypical endothelial receptor, respectively. Activation of alpha(1)-adrenoceptors involves both Ca(2+) influx through L-type and receptor-operated Ca(2+) channels (ROC) and Ca(2+) sensitization mechanisms mediated by protein kinase C (PKC), tyrosine kinases (TKs) and Rho kinase (RhoK). In addition, RhoK can regulate Ca(2+) entry in penile arteries upon receptor stimulation. Vasodilatation of penile arteries and large veins during erection is mediated by neurally released NO. The subsequent increased arterial inflow to the cavernosal sinoids and shear stress on the endothelium lining penile arteries activates endothelial NO production through Akt phosphorylation of endothelial NO synthase (eNOS). NO stimulates guanylate cyclase and increased cyclic guanin 3'-monophosphate (cGMP) levels in turn activate protein kinase G (PKG), which enhances K(+) efflux through Ca(2+)-activated (K(Ca)) and voltage-dependent Ca(2+) (K(v)) channels in penile arteries and veins, respectively. PKG-mediated decrease in Ca(2+) sensitivity and its regulation by RhoK remains to be clarified in penile vasculature. Phosphodiesterase type 5 (PDE5) inhibitors are potent vasodilators of penile resistance arteries and increase the content and effects of basally released endothelial NO. Endothelium-dependent relaxations of penile small arteries also include an endothelium-derived hyperpolarizing factor (EDHF)-type response, which is impaired in diabetes and hypertension-associated ED. Locally produced contractile and relaxant prostanoids regulate penile venous and arterial tone, respectively. The latter activates prostaglandin I (IP) and prostaglandin E (EP) receptors coupled to adenylate cyclase and to the increase of cyclic adenosine monophosphate (cAMP) levels, which in turn stimulates K(+) efflux through ATP-sensitive K(+) (K(ATP)) channels. There is a crosstalk between the cGMP and cAMP signaling pathways in penile small arteries. Relevant issues such as the mechanisms underlying the excitation-secretion coupling of the endothelial cells, as well as those involved in cell proliferation and vascular remodeling of the penile vasculature remain to be elucidated. In addition, only few studies have investigated the changes in structure and function of penile arteries in cardiovascular risk situations leading to ED.
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PMID:Physiological regulation of penile arteries and veins. 1763 89

Phosphodiesterase type 5 (PDE5) induces the breakdown of cyclic guanosine monophosphate (cGMP) in smooth muscle cells. Hence, PDE5 inhibitors promote vasodilative effects by enhancing intracellular cGMP levels. Three PDE5 inhibitors, sildenafil, vardenafil, and tadalafil, have been approved for the treatment of "erectile dysfunction" (ED). All three show an excellent effectiveness regarding ED therapy, but differ from one another regarding their pharmacokinetic properties. Recent experimental studies and clinical trials indicate that PDE5 inhibitors are also effective in the treatment of various other diseases such as pulmonary arterial hypertension (PAH), Raynaud's disease, gastrointestinal disorders, and stroke, and furthermore exert cardioprotective effects. This review describes the cardiovascular safety of PDE5 inhibitors and provides an overview of the current literature regarding potential novel indications.
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PMID:[Novel indications for phosphodiesterase type 5 inhibitors]. 1769 82

Reduced beta-adrenoreceptor signaling is associated with increased sympathoadrenal activity in hypertensive patients and animal models of hypertension. However, the mechanism that accounts for this characteristic decline in beta-adrenergic signaling is unclear. In the present study, we investigated renal phosphodiesterase 4B, which metabolizes cAMP. Immunoblot analysis detected only the phosphodiesterase 4B4 isoform present in kidney tissue from spontaneously hypertensive rats, hypertensive Dahl salt-sensitive (SS) rats, and Dahl salt-resistant rats. The phosphorylated (activated) form of the protein was present at 2-fold greater levels in Dahl SS rats than in spontaneously hypertensive rats and Dahl salt-resistant rats, whereas the unphosphorylated form of the protein was reduced by approximately one half in SS animals. In accord with immunoblot data, rolipram-inhibitable cAMP hydrolyzing activity, a measure of PDE4 activity, was approximately 3-fold greater in kidney cytosolic extracts from SS rats than in extracts from spontaneously hypertensive rats and salt-resistant rats. Phosphodiesterase 4B expression was detected by immunohistochemistry in the renal vasculature, proximal tubules, and distal tubules. These results raise the possibility that increased PDE4 activity, specifically phosphodiesterase 4B4 activity, reduces beta-adrenergic signaling in the kidney and contributes to salt-sensitive hypertension in the Dahl SS rat.
Hypertension 2008 Mar
PMID:Renal phosphodiesterase 4B is activated in the Dahl salt-sensitive rat. 1822 3

Phosphodiesterase (PDE) 5 inhibitors reduce cyclic guanylate monophosphate breakdown, promoting vascular relaxation in the corpora cavernosa and penile erection during sexual stimulation. Sildenafil, vardenafil, and tadalafil were approved as effective treatments for male erectile dysfunction. Because PDE5 is present in artery and vein smooth muscle cells throughout the body, PDE5 inhibitors have mild systemic vasodilatory effects and thus the potential to impact the vascular system. The US Food and Drug Administration has approved PDE5 inhibitors for treating pulmonary hypertension. Moreover, their systemic vasodilating properties theoretically make these drugs suitable for treating hypertension. Studies indicate that PDE5 inhibition may be an option for reducing blood pressure in hypertensive patients. Additional benefits may be related to improved arterial stiffness and endothelial dysfunction, two early vascular abnormalities characterizing essential hypertension. More investigation is needed on PDE5 inhibitors as antihypertensive drugs, especially with slow-release formulations or compounds with long half-life. Studies on safety during long-term administration, interactions with antihypertensive and nonantihypertensive drugs, and effect on target organ damage are needed.
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PMID:Phosphodiesterase 5 inhibition in essential hypertension. 1836 27

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


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