Endothelial dysfunction

Early stages of atherosclerosis include the END, a condition in which the inner layer of blood vessels lose their function. This includes loss of normal endothelium-dependent vasodilation. When acetylcholine – endothelium-dependent vasodilator introduced into normal blood vessels, the endothelium provides nitric oxide (NO), diffuses into smooth muscle cells of blood vessels, which leads to their relaxation. Blood vessels dilate, and blood flow increases. Similar phenomena occur with occlusion of the brachial artery for several minutes (usually with the use of cuffs for measuring blood pressure), followed by spraying of the cuff. In carrying out the Doppler ultrasound marked vasodilation with an increase in the diameter of the brachial artery and blood flow velocity. This normal response is a consequence of inadequate blood flow leading to ischemia. However END reaction vessels to acetylcholine or temporary compression of the brachial artery with subsequent restoration of blood flow is abnormal. Normal coronary arteries expanded in response to the introduction of acetylcholine, which can be found at angiography. The affected artery atherosclerosis is not expanded in response to administration of acetylcholine or marked paradoxical constriction. In patients with vascular disease caused by atherosclerosis itself or its risk factors, a decline severity vasodilation of the brachial artery after it temporarily compression with subsequent reperfusion.

Damage to the endothelium may be due to the large number of different adverse effects. They include the following common risk factors for atherosclerosis: lipid metabolism (increase in total cholesterol, increased low density lipoprotein cholesterol (LDL) cholesterol, decreased HDL cholesterol), smoking, diabetes and hypertension. In addition, may be important as mediators of inflammation, infectious agents, and other factors. These impacts can cause damage to the endothelium, resulting in a violation of synthesis / allocation of NO, increased permeability of the endothelium to lipids and increase the thickness of the endothelium, resulting in adhesion of neutrophils and monocytes to the surface. This endothelial dysfunction occurs before the formation of visible signs of atherosclerosis.
Studies suggest that END is treatable. Reducing the level of lipids in the application of statins, treatment with ACE inhibitors and the use of PDE-5 inhibitor, sildenafil can cause a decrease in expression of END, which is described in more detail in the next section.

Erectile dysfunction is a manifestation endothelial dysfunction
It is believed that about 50% of cases of ED in men older than 50 years are due to cardiovascular disease. Most of them can be associated with END. Experimental studies on rabbits have shown that END can lead to erectile dysfunction, even before the development of atherosclerotic stenosis impeding blood flow in arteries supplying the cavernous bodies. Azadzoi et al., rabbits were fed food with high cholesterol or normal food for them. Then they called an erection in rabbits by introducing cavernous drugs such as phentolamine. Rabbits receiving a normal diet, were able to achieve and maintain an erection with increased cavernous pressure. Rabbits, who were on a diet high in cholesterol, have not been able to maintain an erection, which was confirmed by reduction cavernous pressure. ED also occurred in rabbits that have been formed when angiography revealed stenosis of the arteries, but the most important was the identification of ED in rabbits in which presumably developed in the END result of high blood cholesterol, even before the formation of atherosclerotic narrowings.

Many studies have shown that risk factors for coronary heart disease and hypertension are also risk factors for ED. This is important due to the fact that these risk factors lead to the development of END in the entire vascular system. With its development of atherosclerosis affects various vascular beds. Disorders of lipid metabolism, particularly the low level of HDL cholesterol and high levels of total cholesterol, diabetes, smoking and hypertension (known as risk factors for CHD) are proven risk factors for ED. Obesity and low physical activity are also risk factors for ED. Thus, patients suffering from cardiac disorders or who have risk factors for coronary heart disease, have a higher likelihood of erectile dysfunction, and they should ask questions about the status of their erectile function. On the other hand, in some cases, patients come to doctors looking for treatment of ED. It is important to ask these patients questions about cardiovascular risk factors: whether they suffer from hypertension, lipid metabolism, diabetes? Are they smokers? If these risk factors can be identified and cured, doctors can save the lives of many patients.

Although ED is often associated with many cardiovascular risk factors is widely known that most cardiologists do not ask their patients questions about sexual abuse. The same holds in other medical specialties, including urologists. Kloner et al. conducted a pilot study in collaboration with a large private cardiology center in Los Angeles to determine the prevalence of erectile dysfunction in men with stable chronic coronary artery disease. The study included 66 patients with proven coronary artery disease, many of which were surgical treatment (balloon dilatation with or without stenting or aorto-coronary bypass surgery). Typically, patients answered the questionnaire, waiting for the reception or at home, sending replies by mail. This application is an abridged version of IIEF, contains 5 questions that determine men’s ability to achieve and maintain an erection. All questions were evaluated from 0 to 5 points, and the results summed. Result, less than or equal to 21, seen as a sign of erectile dysfunction. 75% of men took place ED. In addition, 25% of men with erectile dysfunction have suffered severe ED. Thus, erectile dysfunction often accompanies coronary artery disease. Similar results occurred in patients with hypertension (regardless of receiving antihypertensive drugs).

Several studies suggest that patients with ED, even if they do not suffer from angina and had no history of heart attacks are more likely signs of myocardial ischemia during exercise testing. They also have a high probability of presence of risk factors for ED. In connection with what Pritzker proposed the term “penile stresstest. In other words, the development of ED may be an early sign of the presence there of risk factors for coronary heart disease in men.

Erectile dysfunction (ED) – inability to achieve and (or) maintain an erection sufficient for sexual activity. This term was proposed in 1992 by the National Institute of Health of the U.S. instead of the term “impotence” and most accurately reflects the essence of the problem.
ED may be suspected if persistent or recurrent inability to attain and (or) keep an erection occurs in at least half of the cases. Given the pronounced negative impact of ED on quality of life of men, the need for therapy of this disorder is beyond doubt. The most effective among the drugs used to treat erectile dysfunction, now are inhibitors of phosphodiesterase 5-th type (PDE5): sildenafil (viagra), tadalafil (cialis) and vardenafil (levitra). Preparations of this group are modulators of erection: they do not cause it directly, but increase the relaxing effect of nitric oxide through cGMP by blocking the enzyme PDE5. As a result of increased blood flow in the cavernous bodies of the penis occurs and is supported by the physiological erection. It is crucial that in the absence of sexual stimulation, PDE5 inhibitors have no effect. The effectiveness of PDE5 inhibitors demonstrated at practically all forms of ED. However, most patients is accompanied by organic psychogenic factors in the development of sexual disorders. All psychological problems contribute to the weighting of ED. In most cases they are accompanied by aggravating factors, organic erectile dysfunction, at least – the immediate causes of its development. Sexual failure, which is possible in every healthy men is associated with organic sexual dysfunction, and further attempts of sexual intimacy with men waiting there fear of failure. The result is a frequent focus on erection and as a consequence of reduction of psychogenic component of erection. Anxiety occurs in men with partial or random failure during intercourse, ie at the stage of “unreliable” and not “impossible” sufficient erection, resulting in achieving an erection during subsequent sexual intercourse more difficult. As a consequence, often sexual life of patients becomes secondary, which creates prerequisites for the development of “syndrome ED”. All these factors lead to a decrease in motivation psychogenic erectile function. Thus, the optimal treatment of erectile dysfunction is the use of drugs, whose action is least likely to affect the physiological component of psychogenic sexual activity.
Such properties are possessed by the drug Cialis (tadalafil), the main feature of which is the long half-life drug – 17,5 h, which provides a significantly greater duration of its action. The presence of prolonged effect of Cialis has been demonstrated in a multicenter, randomized, double-blind, placebo-controlled study with parallel group study conducted in the United States. 483 men with ED (mean age 58 years) were randomly assigned to six equal groups of treatments (placebo, Cialis 10 mg or Cialis 20 mg) and duration of the drug (24 or 36 hours). The study noted that more than 60% of patients taking Cialis 20 mg, the duration of its effective action was 36 h.

Despite the fact that the time to reach maximum concentration of Cialis in the blood a bit more than with Viagra, it was statistically significant response to the reception teacher ¬ Rata in a dose of 20 mg was observed in 32% of patients at the 16 th minute after administration, while 52% of men — 30 th minute. In contrast to Viagra ingestion and alcohol does not cause delay or deterioration suction Cialis. Thus, when single dose of Cialis were observed effect of the drug on the concentration of alcohol in the blood and blood pressure. In the application of Cialis (20 mg), the average plasma concentration of 378 ng / ml. About 50% of the dose is metabolized under the action of cytochrome P-450, which is characterized by great genetic polymorphism. Removing Cialis provided mainly by the liver, mainly by isoenzyme CYP 3A4 [15]. According to studies, Cialis a carry ¬ comes under good, side effects are usually mild or moderate severity and usually diminish with continued treatment, the frequency cancellation due to adverse events with ¬ put 2,1% in the Cialis group and 1.3% in the placebo group. The most frequently noted headache and dyspepsia (14 and 10% respectively), less often – back pain, nasal congestion, myalgia and ¬ Livs blood to the face.

Cialis has not only a highly effective and well tolerated, but also due to long-term, returns the natural sexual relations. First and foremost is the spontaneity of intercourse and lack of time, depending on dose, as a result of research ¬ tion of psychological aspects of sexual intercourse, it was found that up to 50% of patients prefer not to schedule their sex life in advance. The patient was withdrawn direct psychological dependence on medication and it is possible to maintain the natural sexual life, which is extremely important in the presence of additional psychogenic factors, aggravating ED. For example, a study by Moncada et al. (2003) compared two modes Cialis dosage: three times a week and at the request of the patient. Patients in both groups used a long period of effectiveness of Cialis for the commission of sexual attempts without a clear time dependence of the drug – 73% of sexual attempts in group 1 and 49% in group 2 occurred after 4 h and later after taking the drug. The frequency of sexual attempts was comparable in both groups. The study authors conclude that Cialis effectiveness over a long period allows us to offer a new paradigm of treatment of ED, namely the use of the drug in the exchange rate regime, irrespective of the planned sexual activity.

Given the importance of spontaneity in sexual activity, and research data on the preferences of patients, there have been studies aimed at developing methods for continuous therapy Cialis, based on the fact that after 5 days of continuous reception in the blood plasma reached equilibrium concentration of the drug, sufficient for the development and maintenance of effect with little individual variability. Efficacy and safety of Cialis therapy 1 time a day were evaluated in various multicenter randomized placebo controlled studies in men with ED. Thus, in one study evaluated the efficacy and safety of daily Cialis therapy at a dose of 5 and 10 mg compared with placebo. The study included heterosexual men aged over 18 years with ED, is not less than 3 months. before inclusion in the study. Patients did not use any other methods of treatment of ED. Patients with ED which has developed as a result of hypogonadism, radical prostatectomy (except bilateral nerve preserving prostatectomy), severe renal or hepatic failure, decompensation of diabetes mellitus, unstable angina, requiring admission of nitrates, and cardiac failure in the study were not included. Thus, the study included 268 men who received placebo, Cialis 5 and 10 mg in the ratio 1:2:2, respectively. Treatment lasted for 12-15 weeks. Of the 268 patients completed the study 234 (50 of them received a placebo, 93 – Cialis 5 mg, 91 – Cialis 10 mg). Daily intake of Cialis at a dose of 5 and 10 mg significantly improved erectile function of patients compared with placebo. The effectiveness of the drug did not depend on the initial severity of ED. So, against a placebo increase of IIEF scores averaged 0.9, while on the background of 5 and 10 mg of Cialis – 9,7 and 9,4 (p <0,001). The percentage of patients who responded "yes" to question SEPQ2 ( «Were you able to enter the penis into the vagina partner?"), Against Helicobacter pylori eradication, placebo increased by 11,2%, and background therapy Cialis 5 and 10 mg — at 36,5 and 39,4% respectively. In addition, the percentage of patients who responded "yes" to question SEPQ3 ( «Are there still an erection long enough for successful intercourse?"), Against Helicobacter pylori eradication, placebo increased by 13,2%, and background therapy Cialis 5 and 10 mg – at 45,5 and 50,1% respectively (p <0,001). It should be noted that the complete elimination of ED was achieved only in 8.3% of men treated with placebo, whereas men treated with Cialis in doses of 5 and 10 mg, the complete elimination of ED was achieved in 51,5 and 50,5% respectively. At the same time positively to the question GAQ ("improved if therapy is carried out by your erections?") Answered 28.3% of patients treated with placebo, whereas while taking Cialis at a dose of 5 and 10 mg of the figure was 84,5 and 84, 6%, respectively. Side effects of therapy were expressed mild in 53.8% and a moderate degree in 32.8% of patients. This dyspepsia, headache, back pain, stomach, and myalgia were less common in patients who received Cialis 5 mg (from 2,8 to 6,4%), compared with patients who received Cialis 10 mg ( from 6,7% to 11,4%). Of the 34 patients who discontinued the study, 9 (3,4%) because of side effects (1 because of headache (placebo), and 1 because of headaches and dizziness (Cialis 5 mg), and 1 because of myalgia, headache, dyspepsia and dyspnea, 2 because of abdominal pain (Cialis 10 mg).
In another multicenter placebo-controlled study evaluated efficacy and safety of daily administration of Cialis at a dose of 2.5 and 5 mg in the treatment of ED. The study included 287 men. Exclusion criteria were consistent with those in the study described above. Men who previously received PDE5 inhibitor without effect, as in the study were not included. Patients were randomized into 3 groups: placebo (n = 94), Cialis 2.5 mg (n = 96) and Cialis 5 mg (n = 97). Treatment lasted for 24 weeks, with patients taking the drug at the same time, regardless of sexual activity. Against the background of daily administration of Cialis erectile function of patients improved significantly. Thus, the increase in IIEF scores among patients treated with placebo, Cialis 2.5 and 5 mg was on average 1.2, 6.1 and 7.0, respectively, while the percentage of patients who responded “yes” to question SEPQ2, against the background of Helicobacter pylori eradication amounted to respectively 5.2, 24.3 and 26.2% while for the question SEPQ3 these indicators were 9,5, 31,2 and 35,1% (p <0,001 for all parameters comparisons). At the same time positively to the GAQ question answered 26.1% of patients treated with placebo, whereas while taking Cialis at a dose of 2.5 and 5 mg of the figure was 62,8 and 72,8% respectively. Adverse effects identified in the research process, in most cases were moderate. The most frequent side effects were: nasopharyngitis, gastroenteritis, lower back pain, dyspepsia, gastroesophageal reflux, myalgia, headache and hypertension. Side effects were detected only in 2.4% of patients (placebo – 2 patients, tadalafil 2.5 mg – 2 patients; tadalafil 5 mg – 3 patients). One patient who received Cialis in dose of 2.5 mg, developed myocardial infarction, not leading to death.

Given that erectile dysfunction is a chronic disease requiring ongoing treatment, along with the above-described studies have examined the efficacy and safety of prolonged use by patients Cialis mode 1 time per day. During the study, patients aged over 18 years, with varying degrees and etiology of erectile dysfunction received Cialis 5 mg daily for 1 year (n = 234) or 2 years (n = 238). Indicators of erectile function in patients receiving Cialis for the year improved by an average of 9,6 and 8,4 points, sexual satisfaction – 3,6 and 3,0 points, overall satisfaction – 2,7 and 2,8 points respectively. In addition, a 2-year study of a positive answer to the question GAQ 78,9% of patients. The study did not reveal any serious side effects. The most frequent side effects were: a 1-year study – dyspepsia (9.4%), headache (9.4%), pain (7.3%), flu-like symptoms (5.6%) in 2 -year-old – hypertension (6.3%), nasopharyngitis (5.9%), sinusitis (5.9%) and pain (5.0%).
Thus, at present the choice of ED therapy is large enough. The drug Cialis was necessary number ¬ ethical clinical research, which has proved its effectiveness ¬ efficiency and safety in patients with ED. Cialis 10 and 20 mg of successfully treating erectile dysfunction regardless of initial severity, aetiology and associated diseases. It is well tolerated and is effective up to 36 hours after application, due to the long half-life, it can be taken once a day – a regime that some patients and their partners are less burdensome. Most of the patients and their partners for treatment of ED preferred Cialis compared with other PDE5 inhibitors. The undoubted advantages of the PREPARE ¬ ta can be attributed to a prolonged action, as well as the independence of the effect of food intake and alcohol, allowing the patient to normal life, without changing their habits. In addition, according to current clinical studies, Cialis therapy in the mode 1 time per day is also effective and safe, while the efficiency does not decrease with prolonged use of the drug, and the frequency of side effects comparable to that at the reception as Cialis online on demand, so and other PDE5 inhibitors. The undoubted advantages of this mode of therapy may include a complete lack of psychological dependence on the time of ingestion.

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The enzyme PDE-5 is localized in vascular smooth muscle cells of the corpora cavernosa, as well as in smooth muscle cells of systemic arteries and veins, smooth muscle cells of the gastrointestinal tract and in platelets. Due to the fact that PDE-5 is located in the smooth muscle cells of systemic arteries and veins, with its marked inhibition of mild vasodilation, with the hemodynamic effect resembles the action of weak nitrate. Therapeutic doses of Viagra reduced blood pressure by about 8 mmHg and diastolic pressure by about 5-6 mm Hg. In most cases this reduction is not felt by patients. Viagra reduces systemic vascular resistance and has no appreciable effect on heart rate. It does not increase myocardial contractility and reception in therapeutic doses has no adverse effect on the interval QT. In a study of patients with severe coronary artery disease treated with Viagra in the laboratory for cardiac catheterization, Viagra did not alter the diameter of the coronary arteries and blood flow velocity in them. He showed a weak positive effect on increasing coronary reserve in response to the action of adenosine and did not cause.

Several studies have confirmed the safety of Viagra in patients with coronary artery disease undergoing exercise testing. In one study has even been suggested that Viagra increases the exercise tolerance and increases the ischemic threshold. The importance of these studies is that patients perform exercises with a load comparable to the loads that have occurred during sexual intercourse. Several similar studies have confirmed the safety of Cialis and Levitra in patients with coronary artery disease in the performance of exercise testing.
Early analysis of occurrence of myocardial infarction and death in a double-blind, placebo-controlled studies were comparable in patients receiving Viagra and placebo. Open studies have shown lower rates while taking Viagra compared with placebo. The British study administered substances found no evidence proving the increased frequency of cardiovascular events while taking Viagra have thousands of men, compared with the total male population in England. Similar but less extensive studies Cialis also showed no increase in the frequency of myocardial infarction or death among patients receiving the drug, compared with patients receiving placebo or a similar age group from the general population. FDA has also published data show that mortality among men taking Viagra, was within the expected rates for men of this age. Thus, despite sporadic reports of the development of cardiovascular complications in patients taking Viagra, a thorough analysis of the frequency of such events among patients receiving Viagra, compared with patients of similar age, who may develop erectile dysfunction, has shown that Viagra does not lead to such phenomena. Although sexual activity in rare cases can cause the development of myocardial infarction, the absolute number of such cases is small. Given that Viagra may allow a man to resume sexual activity, different societies, for example, the American College of Cardiology and American Heart Association created a recommendation regarding the appointment of Viagra cardiac patients. In addition to the contraindications to the appointment of Viagra to patients taking nitrates (eg nitroglycerin, isosorbide dinitrate and isosorbide mononitrate), these societies and authors Prinsentonskih conciliatory recommendations believe that we should be wary of the appointment of Viagra in patients with unstable heart disease. It should be noted that this assumption is highly questionable, especially given the fact that patients with unstable heart disease indeed (eg, unstable angina, myocardial infarction and severe heart failure), rarely turn to doctors for the treatment of sexual disorders.

Due to the fact that PDE-5 inhibitors are weak vasodilators, some doctors fear assign them patients taking antihypertensive drugs, for fear of hypotension. Most studies have shown no or little additional reduction in pressure in the appointment of PDE-5 inhibitors in combination with antihypertensive agents. The preparation of the group a-blocker doxazosin, made jointly with PDE-5 inhibitor Viagra, has led to orthostatic hypotension in only a small number of patients that require the abolition of the contraindications to the joint reception of these drugs within 4 hours. Cialis does not lead to additional reduction in blood pressure during the joint reception with amlodipine, but the decrease in pressure observed when combined with angiotensin receptor blockers to. It also led to a slight drop in pressure at admission, together with diuretics, b-blockers and ACE inhibitors. The small reduction in blood pressure also occurred at a joint reception of vardenafil with various antihypertensive drugs. Thus, inhibitors of PDE-5 can lead to a slight decrease in blood pressure. PDE-5 inhibitors are effective in treating erectile dysfunction in patients with arterial hypertension. In general, no significant increase in the frequency and severity of side effects of PDE-5 inhibitors in patients receiving antihypertensive drugs compared with those who have not received them.

Organic nitrates such as nitroglycerin, are NO donors and increase the production of cGMP. PDE-5 inhibitors prevent the collapse of cGMP. In a joint reception of both drugs may increase the level of cGMP, sufficient for the development of significant hypotension in some patients. As a result, nitrates are the only contraindication to receiving Viagra in the United States. Some cases of deaths of patients taking Viagra, were due to the simultaneous intake of nitrates. Interaction with nitrate as described for Cialis, and it is likely that the contraindication regarding the admission of nitrates will be common to the entire class of PDE inhibitors in general. If the patient received Viagra, and he developed an episode retrosternal pain in the recommendations of the conciliation of the American College of Cardiology and American Heart Association indicates that the nitrates can not be applied within 24 hours after taking Viagra to happen drug excretion from the body for period equal to six half-life. Recent preliminary data suggest that interaction with nitrates may disappear within 4 hours after taking Viagra. It is possible that the opportunity to interact with nitrates will be longer while taking Cialis, since the long half-life of the drug is 17.5 hours. If the patient has an inhibitor of PDE-5, and he developed retrosternal pain, there are other antianginalnye / anti-ischemic drugs that can be used instead of nitrate. They include b-blockers, calcium channel blockers, oxygen, acetylsalicylic acid and morphine. Patients with myocardial infarction, who took an inhibitor of PDE-5, can receive conventional treatment (acetylsalicylic acid, thrombolytic therapy, percutaneous intervention) with the exception of nitrates.

Two studies have shown that Viagra can improve endothelial function. In one study, patients with diabetes Viagra improved rapidly decreased dilation of the brachial artery. In addition, the daily intake of Viagra for several weeks resulted in better expansion of blood vessels, which suggests that long term administration may lead to long-term patronage of vascular disease in patients with diabetes. In another study, Katz et al. showed that patients with congestive heart failure have a lower degree of expansion of the brachial artery after compression. Viagra improved the figure, while the effect was dose-dependent.
PDE-5 is distributed in the vessels of the lungs. Several studies have shown that Viagra reduces pulmonary vascular resistance and pressure in the pulmonary artery and improves cardiac output in patients with primary and secondary pulmonary hypertension (which occur with scleroderma and other). Given that pulmonary hypertension poorly to treatment, the emergence of new drugs is viewed with enthusiasm. Sildenafil has an additional positive effect on pulmonary hemodynamics while taking it together with pulmonary vasodilator iloprost or inhalation of NO. Large-scale multicenter studies are currently in the planning stage.
Recent studies suggest that Viagra has the additional advantage of providing improved END in patients with heart failure. Bocchi et al. [48] studied the effect of oral Viagra in 23 patients with congestive heart failure (in most cases 2 and 3 classes) during exercise testing. Viagra reduces heart rate and blood pressure before and during the 6-minute test tredmile. Viagra increased the maximum oxygen consumption during load time and improved performance of exercises with 12.3 to 13.7 minutes (p = 0,003). In the preliminary report Lachmann et al. describe patients with heart failure, performing load cycling with maximum intensity. The next day they performed right heart catheterization. Viagra improved efficiency, maximum oxygen consumption and cardiac output against the background of the exercises. It also reduced the peripheral resistance during rest and increased the stroke volume during rest and during exercise. These data, combined with the data of Katz et al., showing improving vascular function while taking sildenafil, suggest that studies of long-term effectiveness of sildenafil or other PDE-5 inhibitors are quite reasonable in patients with heart failure.

Erectile dysfunction is often a consequence END. Smoking, lipid metabolism, diabetes, hypertension (the same risk factors as for coronary heart disease) are also associated with ED. ED may be an early sign of CHD. PDE-5 inhibitors can effectively treat patients with ED, including patients with atherosclerosis, coronary artery disease and hypertension. Has not been shown that inhibitors of PDE-5 can directly lead to cardiovascular complications. They should not be used in conjunction with nitrates. They are safe for most patients receiving antihypertensive therapy. PDE-5 inhibitors are primarily intended to treat angina, but in the process of research Viagra in these patients improved erections, which is primarily seen as a side effect, the result was the indication for the drug. Apparently, we have come full cycle, as currently developed an interest in application of Viagra in cardiac patients and especially patients with heart failure and pulmonary hypertension. In addition, there are other potential areas of application, as Viagra restores endothelial function and, possibly, has sosudoprotektivnym action. Viagra may be appointed to long-term prescription for patients with peripheral vascular disease and coronary heart disease, as well as a new antihypertensive drug.
Note
Since writing this article, vardenafil has been approved for use in the United States. In connection with the possibility of hypotension, a-blockers and nitrates is a contraindication to its use.