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)

The incidence of erectile dysfunction increases with diabetes, hypertension, hypercholesterolaemia, cardiovascular disease and renal failure. All these conditions are associated with endothelial dysfunction. This review addresses the pathophysiology of erectile dysfunction with a special focus on new insights into nitric oxide (NO)-mediated pathways, oxidative stress and parallels to endothelial dysfunction. NO appears to be the key mediator promoting endothelium-derived vasodilation and penile erection. The possibility is discussed that elevated plasma concentrations of asymmetrical dimethylarginine (ADMA), an endogenous NO synthase inhibitor, may provide an additional pathomechanism for various forms of erectile dysfunction associated with cardiovascular risk factors and disease. Likewise, the role of endothelium-derived factors mediating NO-independent pathways is evaluated.
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PMID:The pathophysiology of erectile dysfunction related to endothelial dysfunction and mediators of vascular function. 1255 45

Sildenafil is the first oral therapeutic agent for erectile dysfunction. Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase (PDE-5). Penile erection involves relaxation of the corpus cavernosum, an event mediated by NO and cGMP. The biological actions of cGMP are terminated by phosphodiesterase enzymes and PDE-5 is the major cGMP metabolising enzyme in this tissue. Sildenafil is relatively safe compared to erection injectables because it does not relax on isolated human corpus cavernosum, and does not cause priapism. Due to the tendency of abuse of sildenafil, its adverse cardiovascular associations with myocardial infaraction, ventricular arrhythmia and hypertension need to be alerted.
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PMID:[Mode of action of sildenafil]. 1256

Nitric oxide (NO) releasing drugs have helped patients suffering from angina pectoris for more than a century. In the 1970s NO-sensitive guanylyl cyclase was identified as the target of NO. Since then, three different isoforms of the enzyme have been identified. All NO-releasing drugs act by binding of NO to the prosthetic heme group common to all three isoforms. They thus act all as isoform-unspecific substances. This review addresses recently developed drugs that activate NO-sensitive guanylyl cyclase independent of NO-release. They have great potential in the treatment of angina pectoris, hypertension and erectile dysfunction. The molecular target has been validated by the successful clinical use of NO-releasing drugs for more than a century. At the same time the mode of action of these drugs is entirely new. The development of highly isoform-specific derivatives with distinct pharmacological profiles is now an open possibility with great potential.
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PMID:Drugs that activate specific nitric oxide sensitive guanylyl cyclase isoforms independent of nitric oxide release. 1257 Jul 2

Erectile dysfunction is a multifactorial condition that may include psychological, neurologic, hormonal, vascular, or cavemosal impairment, or a combination of these factors. Major risk factors include aging, depression, and lifestyle. The diagnosis of erectile dysfunction can be an indicator for undiagnosed diseases, including coronary artery disease, hypertension, and diabetes mellitus. Erectile dysfunction is highly prevalent in the United States, affecting approximately 30 million men. Erectile dysfunction in the majority of men remains undiagnosed, and many men who receive treatment discontinue it because of general dissatisfaction with real-life issues that can have an impact on therapeutic success. Early identification, behavior modification, and increased therapeutic options may improve patient outcomes.
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PMID:Erectile dysfunction: prevalence, etiology, and major risk factors. 1257 34

It has shown that vasoconstriction in the cavernosal circulation is mediated by the RhoA/Rho-kinase calcium sensitization pathway. Inhibition of Rho-kinase activity in cavernosal smooth muscle with Y-27632 resulted in an erectile response marked by elevated intracavernosal pressure (ICP) without a significant change in men arterial pressure (MAP). To explain how erection can occurred in the presence of this strong vasoconstrictive signal, we have hypothesized that nitric oxide (NO) induces vasodilation leading to erection by directly inhibiting activity of the RhoA/Rho-kinase pathway, thereby reducing vasoconstriction. Administration of Y-27632 restored erectile function in rat models of hypogonadism and hypertension, suggesting that Rho-kinase inhibition may have potential clinical value. In addition, our results show that topical application of Y-27632 may be an effective mode of treatment for erectile dysfunction.
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PMID:[Inhibition of tonic contraction of smooth muscle: a new approach to achieve erection dysfunction]. 1259 7

Hypertensive men have a higher prevalence of erectile dysfunction (ED) than the general population. Experimental evidence of ED in hypertensive animals is scarce. This study evaluates the erectile function of spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY) in vivo by the increase in intracavernosal pressure after electrical stimulation of the cavernous nerve (CN) and by isometric tension studies on corporal strips. Frequency-dependent erectile responses to CN stimulations were reduced in SHR. Phenylephrine induced lower corporal contractions in SHR although pD2 values were similar to WKY. Endothelium-dependent relaxations to ACh were impaired significantly in SHR, and indomethacin improved these relaxations in both WKY and SHR, the latter thus reaching values similar to WKY. Corporal relaxations to sodium nitroprusside were enhanced in SHR. Thus a dysfunctional alpha-adrenergic contraction of the corporal smooth muscle, an increased cyclooxygenase-dependent constrictor tone, and/or a defect in endothelium-dependent reactivity are associated with the altered erectile mechanisms in SHR. Drugs targeting endothelial dysfunction may delay the occurrence of ED as a complication of hypertension.
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PMID:Erectile dysfunction in spontaneously hypertensive rats: pathophysiological mechanisms. 1261 93

The clinical expression of ageing involves several organs with variable degrees of precociousness or intensity based on the apparatus or system. An early event in the ageing process may be the occurrence of asymptomatic, and difficult to recognise, periurethral hyperplastic nodules. On the contrary, such an obvious symptom and clinical entity as erectile dysfunction may become a highly relevant herald of ageing. And this will be more so if it appears in coincidence with widespread cardiovascular disease, specially if manifest through hypertension and ischaemic heart disease. The action of the urologist faced with a patient who asks for help for his erectile dysfunction cannot be limited to the evaluation of a simple organ disease.
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PMID:[Aging and urology: is impotence the first symptom of aging?]. 1264 74

Erectile dysfunction (ED) shares the same risk factors as coronary artery disease, so the level of occult cardiovascular risk in men with ED was assessed. A total of 174 men presenting with ED underwent cardiac risk stratification according to the Princeton Consensus Guidelines. Thirty per cent were stratified as intermediate/high cardiovascular risk and had ED treatment deferred until further cardiological assessment; 37% had abnormal lipid profiles; 24% had elevated HbA1C/glucose levels; 17% had uncontrolled hypertension; and 6% were suspected of having significant angina. ED is associated with a high incidence of occult cardiovascular disease. We suggest that cardiologists can significantly contribute to the management of ED.
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PMID:Erectile dysfunction: cardiovascular risk and the role of the cardiologist. 1266 90

The current trends in favor of androgen deprivation therapy (ADT) for nonmetastatic prostate cancer at the stage of biochemical recurrence or increasing prostate-specific antigen (PSA) raises the issue of exposing otherwise asymptomatic patients to potential side effects over the longer term. Some of these side effects can have deleterious effects on quality of life, and others may contribute to increased risks for serious health concerns associated with aging. Sexual side effects are the most well-recognized adverse effects from ADT and include loss of libido, erectile dysfunction (ED), and hot flashes. Loss of libido is distressing to many men, and they may not pursue treatments for ED. However, for those who do maintain sexual interest, various remedies are available. The incidence of hot flashes, which may not abate over the course of ADT, is close to 80%. Estrogens, progestin megestrol acetate, medroxyprogesterone acetate, venlafaxine, and cyproterone acetate have been shown to alleviate hot flashes and associated symptoms. Physiologic effects, including gynecomastia, changes in body composition (weight gain, reduced muscle mass, increase in body fat), and changes in lipids, are less commonly recognized as side effects of ADT. These may lead to an exacerbation of potentially more serious conditions, such as hypertension, diabetes, and coronary artery disease. Loss of bone mineral density, anemia, and hair changes also may occur. Additionally, both the diagnosis of prostate cancer and the hormonal therapy can cause psychological distress. These side effects need more systematic study in clinical trials. Physicians should be aware of far-reaching consequences of ADT and should incorporate strategies for preventing and managing toxicities into routine practice.
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PMID:Side effects of androgen deprivation therapy: monitoring and minimizing toxicity. 1266 85

Erectile dysfunction (ED) is one of the most common diseases of male sexual dysfunction. A cross-sectional study of 388 ED patients who attended six andrology and urology clinics in Jeddah for the first time was performed during a period of 3 months. ED was rated as mild (21% of patients), moderate (60%) or severe (19%), and was strongly associated with age. After adjusting for age, only lack of exercise, alcohol consumption and drug addiction were significantly associated with severity; hypertension, cardiac diseases and smoking were not. About two-thirds of the patients had poor quality of life; severe ED was the only significant predictor of this. Severe ED was not an indicator for co-morbidities.
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PMID:Effect of erectile dysfunction on quality of life. 1269 Jul 73


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