Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erectile dysfunction (ED) is frequent in patients with essential hypertension (EH); a likely common pathogenetic pathway could be a reduced ability of arteriolar vascular smooth muscle (VSM) to relax. Increasing intracellular levels of cGMP reduce the contractile status of VSM; on the contrary, type 5 cGMP-specific phosphodiesterase (PDE5, codified by PDE5A gene) regulates cGMP levels through its clearance. The PDE5A gene represents a good candidate for the intermediate phenotype EH/ED: genetic variants of the PDE5A may predispose to EH and ED and could affect the local and systemic response to sildenafil administration. Thus, a functionally relevant portion of PDE5 5'-flanking promoter region was analyzed by PCR and direct sequencing in patients with EH and idiopathic ED. The sequences obtained showed a T/G polymorphism at position -1142, near an AP1 regulatory element, that was not apparently associated with the intermediate phenotype. We also studied the relationship between this polymorphism and the effects of oral sildenafil on blood pressure (BP) and heart rate (HR) in men with ED. Sildenafil caused a significant decrease of BP, but had no effects on HR; statistical analysis showed no differences in BP and HR variations among PDE5A genotypes. In conclusion, our data showed no correlations of a novel polymorphism of the PDE5A promoter gene with the intermediate phenotype EH/ED and the BP and HR response to sildenafil administration. Further studies are necessary to define the role of this polymorphism and to study the genetic predisposition for EH with ED.
 ...
PMID:Cardiovascular effects of sildenafil in hypertensive men with erectile dysfunction and different alleles of the type 5 cGMP-specific phosphodiesterase (PDE5). 1517 37

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.
 ...
PMID:Phosphodiesterase 5 inhibition in essential hypertension. 1836 27

Phosphodiesterase (PDE) enzymes are widely distributed throughout the body, having numerous effects and functions. The use of on demand PDE5 inhibitors (-Is) for the treatment of erectile dysfunction (ED) has recently obtained approval for chronic daily dosing for the same indication. There are published data supporting the use of PDE5-Is for the treatment of lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). Additional reports suggest benefit by these agents in patients with chronic heart failure, pulmonary hypertension, essential hypertension, and for the treatment of ischemia. Various central nervous system disorders have been described as targets by PDE5-Is. Sildenafil may have a potential therapeutic indication as a cognitive enhancer in age-related cerebral conditions. There is preclinical evidence for further investigation of the use of PDE5A -Is to improve recovery of cerebral function in humans after stroke by enhancing angiogenesis, neurogenesis and improving neurologic function. Sildenafil delays intestinal ulceration by an increase in the secretion of mucus/fluid and a decrease in hypermotility, and has a protective effect in reducing gastric damage. Larger scale, well designed clinical trials are needed to ascertain the safety, efficacy and cost-effectiveness of PDE5-Is in the future treatment of both urologic and non-urologic diseases. In this review, potential applications of PDE5-Is on urologic, cardiovascular, gastrointestinal, and central nervous system disorders will be updated.
 ...
PMID:PDE5 inhibitor treatment options for urologic and non-urologic indications: 2012 update. 2274 25

Endothelial dysfunction precedes the clinical stage of atherosclerotic disease and is recognized as an additional risk factor when detecting symptomatic patients. Endothelial function is largely mediated by nitric oxide, and this vasodilatory mechanism is also responsible for the venous and arterial dilatation required to obtain and maintain an erection. The physiological effects and clinical aspects of sexual function have been extensively studied and reported in patients who have angina or who have experienced a myocardial infarction and in those who have undergone coronary artery bypass graft surgery or heart transplant. The relationship between erectile dysfunction (ED) and the risk factors for coronary heart disease was noted in the Massachusetts Male Aging Study (MMAS). MMAS included 1290 men (aged 40-70 years) and reported a 52% incidence of some degree of ED. Sildenafil and other PDE-5(Phosphodiesterase type-5) inhibitors will eventually be developed for a number of cardiovascular indications including essential hypertension, endothelial dysfunction, ischemia/reperfusion injury, myocardial infarction, ventricular remodelling and heart failure. A recent clinical study suggested that PDE-5 inhibitors might be a new class of drug that can potentially be used for the treatment of essential hypertension. The unique mechanism of action and high efficacy of PDE5 inhibitors has generated immense interest among researchers dealing with sexual dysfunction. The recognition of ED as a warning sign of silent vascular disease has led to the concept that a man with ED and no cardiac symptoms is a cardiac (or vascular) patient until proven otherwise.
 ...
PMID:ERECTILE DYSFUNCTION AS A PREDICTOR OF CARDIOVASCULAR DISEASE. 2813 40