The role of the endothelium in ED has been noted for a number of years and the overlapping of ED and other conditions, especially coronary heart disease, CVD, affecting endothelial function/dysfunction, is clearly present. The endothelial cell is now known to affect vascular tone and impact the process of atherosclerosis, and impacting ED, CVD and peripheral vascular disease.16
For many men, stopping smoking is an erectile dysfunction remedy, particularly when ED is the result of vascular disease, which occurs when blood supply to the penis becomes restricted because of blockage or narrowing of the arteries. Smoking and even smokeless tobacco can also cause the narrowing of important blood vessels and have the same negative impact. 

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Since sexual arousal is a complex process involving hormones, emotions, nerves, muscles, blood vessels and the brain, a malfunction in any of these can lead to ED. Stress, exhaustion and psychological issues can also contribute, and anxiety over maintaining an erection can actually make it harder to attain. In short, any condition that inhibits blood flow to the penis can lead to ED.
The vascular processes that produce an erection are controlled by the nervous system and certain prescription medications may have the side effect of interfering with necessary nerve signals. Among the possible culprits are a variety of stimulants, sedatives, diuretics, antihistamines, and drugs to treat high blood pressure, cancer, or depression. But never stop a medication unless your doctor tells you to. In addition, alcohol, tobacco, and illegal drugs, such as marijuana, may contribute to the dysfunction.
Farag YM, Guallar E, Zhao D, Kalyani RR, Blaha MJ, Feldman DI, Martin SS, Lutsey PL, Billups KL, Michos ED. Vitamin D deficiency is independently associated with greater prevalence of erectile dysfunction: The National Health and Nutrition Examination Survey (NHANES) 2001-2004. Atherosclerosis. 2016 Sep;252:61-7. doi: 10.1016/j.atherosclerosis.2016.07.921. Epub 2016 Jul 29.
The dorsal artery provides for engorgement of the glans during erection, whereas the bulbourethral artery supplies the bulb and the corpus spongiosum. The cavernous artery effects tumescence of the corpus cavernosum and thus is principally responsible for erection. The cavernous artery gives off many helicine arteries, which supply the trabecular erectile tissue and the sinusoids. These helicine arteries are contracted and tortuous in the flaccid state and become dilated and straight during erection. [9]
Iatrogenic hypotension can occur in men in neurodegenerative disease using sildenafil (49). Hussain et al. placed men with PD and MSA on sildenafil and recorded blood pressure before and after. Half of the 12 MSA patients developed postural hypotension, while none of the twelve PD patients did. Since MSA can be difficult to distinguished diagnostically from PD, baseline blood pressure measurements prior to prescribing the medication and seeking medical assistance if symptomatic hypotension occurred was recommended for all patients with PD, and MSA. Of note, none of the men with MSA who developed hypotension discontinued sildenafil use due to its effectiveness at improving their erections.
PDE5i for ED in patients with MS can be considered as reasonably effective and safe. Fowler et al. performed a randomized, multicenter, double-blind, flexible dose trial with open label extensions comparing sildenafil to placebo (75). A nearly 4-fold increase in effective erections was noted in the treatment arm, 96% vs. 24%. Sexual satisfaction and overall satisfaction were also improved in the treatment group based on IIEF scores, and quality of life assessments. Lombardi et al. evaluated tadalafil use in men with MS (71). Seventy eight percent of the men responded with improved erections, better quality of life with regards to sexual function, partner relationship and family life. Just less than half the men who responded to the tadalafil did so at the lower dosage of 10 mg. Subjects in either studies did not have any significant adverse side effects beyond flushing, and headache with PDE5i use.
All NOS subtypes produce NO, but each may play a different biologic role in various tissues. nNOS and eNOS are considered constitutive forms because they share biochemical features: They are calcium-dependent, they require calmodulin and reduced nicotinamide adenine dinucleotide phosphate for catalytic activity, and they are competitively inhibited by arginine derivatives. nNOS is involved in the regulation of neurotransmission, and eNOS is involved in the regulation of blood flow.
With drug therapy, there’s a risk of side effects such as headaches, back pain or an upset stomach. Before taking any medication for erectile dysfunction it is important to ensure your doctor is ok with that decision. Medication may not work for all men, for instance, if you have diabetes or have previously had prostate surgery. ED medication might also have serious risks if you’re currently taking nitrates (commonly prescribed for chest pain), have heart disease or have low blood pressure.22

Psychological Causes of ED – Between 10% and 20% of ED cases have a psychological cause. Because arousal starts in the brain, psychological issues can be a significant contributing factor to erectile dysfunction. Mental health conditions like depression or anxiety can negatively impact your libido, making it more difficult for you to become aroused.
As is true in so many medical conditions, lifestyle modifications, considered first-line therapy, can have a salutary effect in ED management, and men should be encouraged to make the necessary changes to the benefit of their sexual function and to their overall health as well. Despite the benefits of behaviour modification, men presenting with ED want the physician to help with measures that can have an immediate impact.

For many men, stopping smoking is an erectile dysfunction remedy, particularly when ED is the result of vascular disease, which occurs when blood supply to the penis becomes restricted because of blockage or narrowing of the arteries. Smoking and even smokeless tobacco can also cause the narrowing of important blood vessels and have the same negative impact. 

These are not currently approved by the FDA for ED management, but they may be offered through research studies (clinical trials). Patients who are interested should discuss the risks and benefits (informed consent) of each, as well as costs before starting any clinical trials. Most therapies not approved by the FDA are not covered by government or private insurance benefits.
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