Cardiovascular risk factors, erection disorders and endothelium dysfunction

Upon sexual stimulation, penile erection, occurring in response to the activation of pro-erectile autonomic pathways, is greatly dependent on adequate inflow of blood to the erectile tissue and requires coordinated arterial endothelium-dependent vasodilatation and sinusoidal endothelium-dependent corporal smooth muscle relaxation. Nitric oxide (NO) is the principal peripheral pro-erectile neurotransmitter which is released by both non-adrenergic, non-cholinergic neurons and the sinusoidal endothelium to relax corporal smooth muscle through the cGMP pathway. Any factors modifying the basal corporal tone, the arterial inflow of blood to the corpora, the synthesis/release of neurogenic or endothelial NO are prime suspects for being involved in the pathophysiology of erectile dysfunction (ED). In fact, conditions associated with altered endothelial function, such as ageing, hypertension, hypercholesterolemia and diabetes, may, by changing the balance between contractant and relaxant factors, cause circulatory and structural changes in penile tissues, resulting in arterial insufficiency and defect in smooth muscle relaxation and thus, ED. There is increasing evidence to suggest that ED is predominantly a vascular disease and may even be a marker for occult cardiovascular disease. Recent results illustrating the importance of endothelial dysfunction in the pathophysiology of different forms of experimental ED are discussed. These pathways may represent new potential treatment targets.

Current role of penile implants for erectile dysfunction.

PURPOSE OF REVIEW: The purpose of this review is to appraise new developments and publications in the field of penile prosthetic surgery. Urologists dealing with erectile dysfunction need to recognize the value of penile prosthetic surgery as a very efficacious treatment for this common condition. This type of surgery is needed in a considerable proportion of patients with erectile dysfunction so this review is timely and relevant. RECENT FINDINGS: The main themes in the literature covered include risk factors for infection of penile prostheses, its prevention with the use of hydrophilic and antibiotic-coated prostheses, particularly in re-operations, and its management with the new rescue procedures. Surgical tips for prosthetic surgery are also reviewed as well as clinical outcomes and factors influencing them. SUMMARY: Of all the invasive treatments currently available, placement of a penile prosthesis is one of the most successful, giving high levels of satisfaction. With the aid of new technical advances, the risk of infection--the most feared complication--can be minimized so prosthetic surgery may play a major role in the treatment of erectile dysfunction.

Phosphodiesterase 5 enzyme and its inhibitors: update on pharmacological and therapeutical aspects.

Cyclic nucleotides are important secondary messengers that control many physiologic processes, including smooth muscle contractility. Phosphodiesterases (PDEs) comprise of a superfamily of metallophosphydrolases that specifically cleave the 3',5'-cyclic phosphate moiety of cAMP and/or cGMP to produce the corresponding 5' nucleotide. Currently 21 PDE genes have been cloned and are classified into 11 families (1-11) according to their sequence of homology, biochemical and pharmacological properties. Phosphodiesterase type 5 (PDE5) is one of the members of the superfamily that specifically cleaves cyclic guanosine monophosphate (cGMP), a key intracellular secondary messenger. It is composed of 875 amino acids and was first identified in lungs, vascular and tracheal smooth muscle, and platelets. PDE5 is selectively inhibited by sildenafil, Vardenafil ( Levitra ) and Tadalafil ( Cialis ) , and less selectively by zaprinast and dipyridamole. PDE5 inhibitors have been reported to possess antiplatelet aggregation, weak cardiac inotropic effects and vascular relaxant properties. The tissue distribution of the PDE5 family is relatively restricted compared with other PDEs. Still, recent immunohistochemical and reverse transcriptase-polymerase chain reaction analysis have demonstrated the presence of anti-PDE5 antibodies and PDE5 transcripts in rat cerebellum, kidney, pancreas, aortic smooth muscle cells, heart, placenta, skeletal muscle, and, to a much lesser extent, in other regions of the brain, liver and lungs. Research in this field is intense, with a goal of identifying and developing new, selective PDE5 inhibitors that would be beneficial in a number of maladies, as well as angina, hypertension and erectile dysfunction (ED). 2004 Prous Science.

Effect of antihypertensive agents on quality of life in the elderly.

Management of hypertension in the elderly should take into account, in particular, the possible negative impact of antihypertensive drugs on the patient's quality of life, the deterioration of which may result in a loss of independence and reduced treatment compliance. Quality of life is recognised as a multifactorial variable and can be subdivided into different domains (symptomatic well-being, emotional, physical, work-social, cognitive and life satisfaction), which are generally explored by means of specific questionnaires or scales. When evaluating elderly patients with hypertension, it is necessary to pay particular attention to specific domains such as symptomatic well-being, cognitive function, activity and sexual function, which have already been diminished by the age itself and the disease. The results of some large trials that specifically evaluated the quality of life effects of long-term therapy of hypertension in older people (Medical Research Council's [MRC] Trial of Hypertension in Older Adults, Systolic Hypertension in the Elderly Program [SHEP], Systolic Hypertension in Europe [Syst-Eur], Study on COgnition and Prognosis in the Elderly [SCOPE]) have shown that antihypertensive treatment as a whole either had no negative impact on quality of life, or even produced some improvement. The question whether some classes of antihypertensive agents are more beneficial or harmful than others in terms of quality-of-life effects remains largely unanswered.Results from long-term trials suggest that treatment with diuretics is not associated with adverse effects on quality of life. Nevertheless, chlortalidone and other diuretics have been more often associated with sexual dysfunction in men, including decreased libido, erectile dysfunction and difficult ejaculation, than other drug classes. Nonselective lipophilic beta-adrenoceptor antagonists, such as propranolol, have been reported to exert some negative effect on quality of life and have been associated with depression, impairment of memory function and adverse effects such as erectile problems. A less unfavourable impact has been described with beta(1)-adrenoceptor antagonists and those with vasodilating properties. Calcium channel antagonists have generally been associated with a positive effect on quality of life, although some trials have shown high rates of adverse effects and withdrawals, particularly with first-generation dihydropyridines. Concern has also been raised about the potential for adverse cognitive effects associated with the use of calcium channel antagonists, but studies on this topic are not univocal. ACE inhibitors have usually been reported to exert favourable effects on quality of life. These drugs seem to be effective in maintaining, or even improving, cognitive function through mechanisms other than blood pressure control. In addition, a number of studies reported favourable impact of ACE inhibitors on sexual function. Angiotensin II receptor antagonists have been associated with good tolerability and low withdrawal rate. They have been demonstrated not to interfere with or even improve cognitive function as well as sexual performance.Although no class of antihypertensive agents presents a clearly superior effect over the others in terms of quality of life, the current impression is that ACE inhibitors and angiotensin II receptor antagonists may offer some advantage, at least in regard to effects on cognitive function and sexual activity.