authors and five references. They should not have tables or figures and should relate solely to an article published in Circulation within the preceding 12 weeks. Only some letters will be published. Authors of those selected for publication will receive prepublication proofs, and authors of the article cited in the letter will be invited to reply. Replies must be signed by all authors listed i...

Background. The present study was designed to investigate the intracellular production of cyclic GMP (cGMP) in platelets in response to nitroglycerin and to determine the potential clinical value of platelet cGMP as an indicator of the effects of nitroglycerin and nitrate tolerance. Methods and Results. Platelet cGMP levels and the diameters of the coronary arteries before and 2 minutes after i...

OBJECTIVES Nitroglycerin (NTG) is metabolized to nitric oxide (NO) in vascular smooth muscle cells. It is currently not clear whether prolonged exposure to NTG and tolerance development directly affects endogenous NO-mediated vasodilation in vivo. This study investigates NO-mediated vasodilation in conscious chronically catheterized rats before and after development of nitrate tolerance. The ef...

Nitrates such as nitroglycerin (GTN) and nitric oxide donors such as S-nitrosothiols are clinically vasoactive through stimulation of soluble guanylyl cyclase (sGC), which produces the second messenger cGMP. Development of nitrate tolerance, after exposure to GTN for several hours, is a major drawback to a widely used cardiovascular therapy. We recently showed that exposure to nitric oxide and ...

Background and Objectives:Time-phasic development of nitrate tolerance in cardiovascular diseases is very important because it can contribute to the advent of blunted vasodilation or rebound ischemia even during continuous NTG treatment. In such a condition, we should change the therapeutic regimen of nitrate treatment to prevent the worsening of symptoms. Materials and Methods:We created a nit...

Organic nitrates have served as mainstays of therapy for the treatment of coronary artery disease for more than a century. Their use, however, has been complicated by unwanted side effects, including hypotension and the development of nitrate tolerance. Nitrate tolerance is a term used to define tachyphylaxis to nitrates with long-term use. The mechanisms of nitrate tolerance have been debated ...

Organic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which occurs during chronic treatment with these agents. The mechanisms underlying nitrate tolerance remai...

The clinical use of hydralazine in combination with organic nitrates has resulted in a beneficial effect on survival, cardiac function, and exercise tolerance. More recently, hydralazine has been shown to prevent development of nitrate tolerance and early attenuation of nitrate-mediated hemodynamic effects in both experimental animals as well as patients with severe heart failure due to depress...

OBJECTIVES To investigate the effect of chronic antioxidant treatments on the development of nitrate tolerance in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats by evaluating (i) coronary vascular reactivity, (ii) lipid peroxidation (malondialdehyde), and (iii) peroxynitrite formation (3-nitrotyrosine). METHODS Tolerance was induced in 16-week-old male SHR and WKY, ...