Usefulness of losartan, captopril, and furosemide in preventing nitrate tolerance and improving control of unstable angina pectoris

Cotter, Gad; Metzkor-Cotter, Einat; Kaluski, Edo; Blatt, Alex; Litinsky, Irena; Baumohl, Yehuda; Moshkovitz, Yaron; Vered, Zvi; Golik, Ahuva

doi:10.1016/s0002-9149(98)00548-7

Cited by 15 publications

(8 citation statements)

References 15 publications

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“…Cotter et al demonstrated in normotensive patients with unstable angina that Losartan affected nitrate tolerance only partially at 48 hrs after administration [25]. On the other hand, Milone et al more recently concluded from a randomized, double-blind, parallel study involving healthy subjects, that Losartan did not prevent the development of hemodynamic and vascular tolerance to nitroglycerin [26].…”

Section: Losartan and Prevention Of Nitrate Tolerance: Clinical Studiesmentioning

confidence: 99%

Angiotensin II-Receptor Antagonist Losartan Does not Prevent Nitroglycerin Tolerance in Patients with Coronary Artery Disease

Longobardi

Ferrara

Leosco

et al. 2004

Cardiovasc Drugs Ther

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The study evaluated the effect of Losartan in preventing nitrate tolerance during continuous transdermal nitroglycerin (TD-GTN) therapy in patients with coronary disease. Fifteen subjects with chronic stable ischemia evaluated by exercise test, were randomized to 28 days of TD-GTN 20 mg once a day without free interval plus Losartan 100 mg or Losartan-placebo with a double blind crossover design. Myocardial ischemic parameters during stress test were evaluated after each test period and results of Losartan therapy were compared to those with placebo. Time to onset 1 mm ST-depression was significantly higher after acute TD-GTN 20 mg with respect to placebo run-in, sustained TD-GTN 20 mg plus Losartan 100 mg or Losartan-placebo (p < 0.001). ST-depression at peak exercise and time to recovery of ST segment were markedly lower after acute TD-GTN 20 mg compared to placebo run-in (p < 0.05), sustained TD-GTN 20 mg plus Losartan 100 mg (p < 0.001) or Losartan-placebo (p < 0.05). At 1 mm-ST depression and at peak exercise, systolic blood pressure and rate-pressure product significantly decreased after sustained TD-GTN 20 mg plus Losartan 100 mg (p < 0.001, p < 0.05 respectively) with respect to placebo run-in, acute and sustained TD-GTN 20 mg plus Losartan-placebo. Moreover at peak exercise, these data were also observed after acute TD-GTN 20 mg compared to placebo run-in and sustained TD-GTN 20 mg plus Losartan-placebo (p < 0.001). The AT(1) antagonist Losartan administration does not prevent the development of nitrate tolerance during continuous TD-GTN therapy.

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Section: Losartan and Prevention Of Nitrate Tolerance: Clinical Studiesmentioning

confidence: 99%

Angiotensin II-Receptor Antagonist Losartan Does not Prevent Nitroglycerin Tolerance in Patients with Coronary Artery Disease

Longobardi

Ferrara

Leosco

et al. 2004

Cardiovasc Drugs Ther

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“…The ACE inhibitors appear to have the advantage in two clinical scenarios: 1) angina pectoris and nitrate tolerance [63] and 2) fibrinogen levels and insulin resistance in overweight hypertensive patients [64]. No major differences between agents were seen in a clinical study of baroreceptor dysfunction [65].…”

Section: Effects Of Ace Inhibitors Versus Arbs In Other Diseasesmentioning

confidence: 99%

Therapeutic trials comparing angiotensin converting enzyme inhibitors and Angiotensin II receptor blockers

Elliott

2000

Current Science Inc

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Two independent pharmacologic methods of specifically interfering with the renin-angiotensin-aldosterone system have been brought to the marketplace: angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). These agents have the potential not only to be very widely used for a broad variety of clinical indications but also to compete against each other as treatments for hypertension, heart failure, renal impairment, and other conditions. Many short-term comparative studies of these two classes of drugs have now been completed. Most have focused on surrogate endpoints, such as blood pressure, renal function, or cough. These studies have generally concluded that ARBs are better tolerated but that the two drug classes otherwise have similar efficacy. The largest clinical trial comparing ARBs and ACE inhibitors thus far completed, Evaluation of Losartan in the Elderly (ELITE 2), failed to confirm the results of a smaller study; it did not demonstrate a significant improvement in outcomes (death or hospitalization for heart failure) with an ARB used alone, despite better tolerability. Many longer-term outcome studies with survival endpoints are under way, but most will compare the combination against an ACE inhibitor alone. These studies will define the optimal use of these agents in medicine for decades to come.

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“…While several studies showed that angiotensin-converting enzymes inhibitors (ACEIs) or Ang II- receptor antagonists can reverse or prevent of nitrate tolerance (Cotter et al, 1998), this beneficial effect was not always observed (Dakak et al, 1990; Longobardi et al, 2004). In larger clinical trials, such as GISSI-3 and ISIS 4, there was no significant evidence that the effect of nitrate therapy was different in the presence or absence of ACEIs.…”

Section: Discussionmentioning

confidence: 99%

Dissociation between Superoxide Accumulation and Nitroglycerin-Induced Tolerance

Tsou¹,

Addanki²,

Fung³

2008

J Pharmacol Exp Ther

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We hypothesize that superoxide (O 2 . ) accumulation is not a crucial causative factor in inducing nitroglycerin (NTG) . accumulation may be an effect, rather than an initiating cause, of NTG tolerance.Nitroglycerin (NTG; glyceryl trinitrate) and other organic nitrates have been widely used to treat coronary artery disease in patients with stable and unstable angina, acute myocardial infarction, and congestive heart failure. When administered acutely, NTG relieves ischemic symptoms rapidly without serious side effects. However, its efficacy after repeated dosing is attenuated because of the development of pharmacologic tolerance. This phenomenon was first described by Stewart (1888) in the 19th century, but its underlying mechanism(s) still remained incompletely defined.Nitrate tolerance is a complex phenomenon accompanied by a myriad of events, including decreased pharmacological response, reduced metabolism, increased oxidative stress, altered gene expression, etc. Consequently, several hypotheses have been proposed to account for these various phenomenon, including those of sulfhydryl depletion, impaired biotransformation of mitochondrial aldehyde dehydrogenase (aldehyde dehydrogenase 2; ALDH2), and oxidative stress, as reviewed recently in Fung (2004) and Mü nzel et al. (2005).Mü nzel et al. (1995) found that a prolonged period of NTG exposure in rabbits enhanced superoxide (O 2 . ) production in the blood vessel wall, and they proposed that nitrate tolerance was caused by increased O 2 . formation. Further development of this mechanism, which became known as "the O 2 . -oxidative stress hypothesis," suggested that chronic NTG treatment increases angiotensin II (Ang II) binding to endothelium angiotensin receptors, subsequently stimulating NADPH oxidase (NOX) to produce O 2 . . This oxygen-free radical then reacts with nitric oxide (NO), the putative intermediate of NTG, to form peroxynitrite, an oxidant and a weaker vasodilator than NO. Oxidative stress also brings about uncoupling of endothelial NO synthase (eNOS), resulting in decreased NO availability and further O 2

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Usefulness of losartan, captopril, and furosemide in preventing nitrate tolerance and improving control of unstable angina pectoris

Cited by 15 publications

References 15 publications

Angiotensin II-Receptor Antagonist Losartan Does not Prevent Nitroglycerin Tolerance in Patients with Coronary Artery Disease

Angiotensin II-Receptor Antagonist Losartan Does not Prevent Nitroglycerin Tolerance in Patients with Coronary Artery Disease

Therapeutic trials comparing angiotensin converting enzyme inhibitors and Angiotensin II receptor blockers

Dissociation between Superoxide Accumulation and Nitroglycerin-Induced Tolerance

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