For both men and women an inverse relationship between the level of physical activity and incidence of cardiovascular disease, which persists after controlling for other risk factors, has been clearly demonstrated. Furthermore, those with established disease participating in exercise rehabilitation programmes have shown lower mortality rates.
Douglas Seals of the University of Colorado at Boulder, USA, reviewing what is currently known about the role of nitric oxide in the regulation of vascular tone, said that physical exercise increases blood flow resulting in increased shear stress on the surface of the endothelium. The sustained increase in shear stress is believed to elicit an adaptive response in which both the gene expression and phosphorylation of nitric oxide synthase (the enzyme responsible for nitric oxide production) increase. Endothelium-derived nitric oxide exerts a plethora of anti-atherosclerotic functions, not only promoting vasodilation but also having important anti-inflammatory and anti-thrombotic effects.
Studies have demonstrated increased plasma and urinary concentrations of the major stable nitric oxide metabolites (nitrate and nitrite) after aerobic exercise training programmes. Seals, who studies the effects of habitual aerobic exercise on vascular function in older adults, believes that improvements in nitric oxide are a key mechanism involved. "There are multiple lines of evidence that regular aerobic exercise improves the function and health of arteries largely by improving the bioavailability of nitric oxide."
One problem, according to fellow speaker Volker Adams from Leipzig, Germany, is that we currently have no idea how much exercise is needed to produce sufficient quantities of nitric oxide to bring about these beneficial effects. Adams and the European Association for Cardiovascular Prevention & Rehabilitation (EACPR), an association of the ESC, are planning a a study randomising patients with chronic heart failure to either normal aerobic exercise training or intensive muscular strength training combined with endurance training. The investigators hope to see whether patients undergoing these two distinct levels of exercise show any difference in nitric oxide production. "The study is important because, if we can show the minimum level of exercise likely to achieve benefits, we're far more likely to be able to persuade patients to undertake exercise," says Adams.
Ulf Landmesser from Zurich, Switzerland, presented studies showing that statins and angiotensin receptor blockers (ARBs) upregulate the expression of nitric oxide synthetase, thereby increasing nitric oxide production. “We also have new evidence suggesting that treatment with nicotinic acid not only increases HDL plasma levels, but also improves HDL's vasoprotective effects, which in turn stimulates endothelial nitric oxide,” he said.
“The message is that if you are healthy you should take exercise for your heart health, but if you have pre-existing coronary artery disease you should also be taking a statin and an ACE-inhibitor or ARB. For high risk patients exercise is not enough,” says Landmesser.also believes that exercise confers additional benefits over pharmaceutical treatment. "When we analysed patients with heart disease taking optimum medication we still managed to show exercise increased their nitric oxide levels," he said.