Effect of losartan on human platelet activation

Guerra-Cuesta, José I.; Montón, Mercedes; Rodríguez-Feo, Juan A.; Jiménez, Ana; González-Fernández, Fernando; Rico, Luís; Gómez, R; Farré, Jerónimo; Casado, Santos; López‐Farré, Antonio

doi:10.1097/00004872-199917030-00019

Cited by 62 publications

(49 citation statements)

References 17 publications

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“…36 Several angiotensin receptors blockers demonstrate not profound, but still evident antiplatelet effect. 10,37,38 Aliskiren ((2(S),4(S),5(S),7(S)-N-(2-carbamoyl-2-methylpropyl)-5-amino-4-hydroxy-2,7-di-isopropyl-8-[4-methoxy-3-(3-methoxypropoxy)phenyl]-octanamid hemifumarate)), an octanamide, is the first representative of a new class of completely nonpeptide, low molecular weight, orally active transition state renin inhibitors. 39 Aliskiren effectively reduces blood pressure in patients with arterial hypertension 40,41 regardless of their racial origin, 42 and reduces production of angiotensin I-II in a dosedependent manner.…”

Section: Discussionmentioning

confidence: 99%

Effects of aliskiren, a renin inhibitor, on biomarkers of platelet activity, coagulation and fibrinolysis in subjects with multiple risk factors for vascular disease

et al. 2008

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Aliskiren, an octanamide, is nonpeptide, low molecular weight, orally active renin inhibitor effectively preventing angiotensin and aldosterone release. This drug has been recently approved for the treatment of hypertension. Considering potential links between hypertension, platelets, the coagulation cascade and fibrinolysis we sought to evaluate the effect of aliskiren on human biomarkers of hemostasis. In vitro effects of whole blood preincubation with escalating concentrations of aliskiren (500, 1000 and 2000 ng ml À1) were assessed in 20 aspirin-naive volunteers with multiple risk factors for vascular disease. A total of 33 biomarkers were measured, of which 18 are related to platelet function, 12 to coagulation and 3 to fibrinolysis. Pretreatment of blood samples with aliskiren 500 ng ml À1 resulted in a significant increase of antithrombin-III (AT-III) activity (P ¼ 0.003). All other tested biomarkers were not significantly affected. Spiking whole blood with the higher aliskiren doses was associated with various trends in biomarker activity, where 1000 ng ml À1 concentration mostly decreased (7/33), and 2000 ng ml À1 mostly increased (6/33) some biomarkers. In the therapeutic concentration of 500 ng ml À1 aliskiren does not affect hemostatic biomarkers, except for a moderate but highly significant (P ¼ 0.003) increase of AT-III activity. Higher aliskiren doses were associated with more profound biomarker changes, but they are likely not to be clinically relevant since they show diverging (that is, both mild antiplatelet and platelet-activating) trends, and considering the 2-to 4-fold safety margin. It is suggested that antithrombotic properties of aliskiren be explored further in an ex vivo clinical setting.

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Section: Discussionmentioning

confidence: 99%

Effects of aliskiren, a renin inhibitor, on biomarkers of platelet activity, coagulation and fibrinolysis in subjects with multiple risk factors for vascular disease

et al. 2008

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“…[36][37][38][39][40] 28,30,33 and especially in elderly patients with isolated systolic hypertension. 29,31 Other mechanisms by which ARBs could reduce the incidence of new or recurrent stroke include the beneficial effects of some ARBs on blood glucose control by increasing insulin sensitivity, 49,50 their platelet antiaggregating effects, [51][52][53][54] their hypouricemic effects 66,67 and their atrial antifibrillatory effects. [69][70][71] All these actions of ARBs could add to their AII-mediated stroke protective effects.…”

Section: Discussionmentioning

confidence: 99%

“…Recent experimental studies have shown that losartan interacts with the TXA 2 /PGH 2 receptor in human platelets and also platelet activation by the TXA 2 agonist U46619 was significantly inhibited by losartan dosedependently. 51 Losartan also blocks the action of P-selectin on platelet adhesion. P-selectin is an adhesion protein that is stored in the alpha granules of platelets, and platelets from SHR-SP have a higher expression of P-selectin and a higher ability to adhere to synthetic and endothelial surfaces than platelets from normotensive WKY rats.…”

Section: Aii-mediated Effects Of Arbsmentioning

confidence: 99%

Possible pathophysiologic mechanisms supporting the superior stroke protection of angiotensin receptor blockers compared to angiotensin-converting enzyme inhibitors: clinical and experimental evidence

Chrysant

2005

J Hum Hypertens

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Stroke is a major cause of death and disability and its incidence increases linearly with age and the level of systolic and diastolic blood pressure. Stroke, besides being a cause of long-term disability for the affected person, also imposes a significant burden on society and healthcare costs. Although good blood pressure control is very critical for stroke prevention, angiotensin receptor blockers (ARBs) may be superior to angiotensin-converting enzyme inhibitors (ACEIs) for the same degree of blood pressure control. This hypothesis has clinical and experimental support. ARBs prevent stroke incidence by blocking the angiotensin II (AII), AT 1 receptors preventing brain ischaemia and allowing AII to stimulate the unoccupied AT 2 receptors, which improve brain ischaemia. ACEIs, by reducing AII generation, are less effective in preventing stroke. This hypothesis provides evidence that AII plays an important role in the prevention of stroke. Certain ARBs like losartan, and telmisartan, irbesartan and candesartan possess additional properties which may play a role in stroke prevention, which is independent of AII. These include antiplatelet aggregating, hypouricemic, antidiabetic and atrial antifibrillatory effects. However, the most critical factor in stroke prevention is good blood pressure control irrespective of drug used.

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“…9 Both telmisartan and losartan have platelet antiaggregatory activity that is not shared by valsartan's, candesartan's, or losartan's major metabolite, EXP3174. [10][11][12][13] Losartan also reduces uric acid, an end-product of purine metabolism linked to the progression of renal disease 14 and increased CV risk 15 and implicated in the development of hypertension in children. 16 It has been hypothesized that these pleiotropic effects of specific ARBs could contribute to the lower incidence of stroke than predicted by BP reduction in outcomes trials of hypertensive patients treated with ARBs compared with treatment with other antihypertensive drugs.…”

Section: Pharmacologic Actions Unique To Specific Arbsmentioning

confidence: 99%

Angiotensin Receptor Blockers: Pharmacology, Efficacy, and Safety

Taylor

Siragy

Nesbitt

2011

The Journal of Clinical Hypertension

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Key Points and Practical Recommendations• The angiotensin receptor blockers are highly effective antihypertensive agents that are also particularly well tolerated.• There are no major differences in efficacy or other clinical characteristics among older drugs in this class, although some of the newer agents may more effectively reduce blood pressure than older agents.• Major randomized clinical trials have demonstrated that angiotensin receptor blockers provide significant outcomes benefits in conditions such as diabetic nephropathy, chronic heart failure or heart failure following myocardial infarction, hypertension with left ventricular hypertrophy and in patients whose histories of previous events or complicated diabetes puts them at high cardiovascular risk.• In treating hypertension, angiotensin receptor blockers can be used as first-line therapy or added at later stages of treatment titration.• These drugs are very effective in combination with thiazide diuretics or calcium channel blockers and there are several single-pill, fixed-dose combinations of angiotensin receptor blockers with hydrochlorothiazide, amlodipine, or aliskiren. These combinations can be given as initial therapy (where appropriate) or later in the course of treatment. Three-drug combinations (angiotensin receptor blocker plus amlodipine plus hydrochlorothiazide and angiotensin receptor blocker plus aliskiren plus hydrochlorothiazide) are also available. J Clin Hypertens (Greenwich). 2011;13:677-686. Ó2011 Wiley Periodicals, Inc.The renin-angiotensin-aldosterone system (RAAS) plays an important role in protecting vertebrates against cardiovascular collapse due to hypotension and volume loss in the event of traumatic injury that involves blood loss. In certain humans, however, inappropriate or exaggerated activity of the RAAS contributes to the development of hypertension and the initiation of a molecular cascade in tissues with consequent injury to critical organs such as the brain, kidneys, heart, and blood vessels. 1-3 As understanding of the pathologic role of the RAAS in hypertensive vascular disease has unfolded during the past century, so has the interest in developing drugs that could interdict specific components of the RAAS. The first of the RAAS-blocking drugs to become commercially available were the aldosterone antagonists in the 1970s, followed by the angiotensin-converting enzyme (ACE) inhibitors in the 1980s and the angiotensin II receptor blockers (ARBs) in the 1990s. Unlike ACE inhibitors that inhibit the conversion of angiotensin I to II, ARBs bind to the angiotensin II AT 1 receptor, thereby inhibiting the cellular actions of angiotension II mediated by the receptor in which the tissue is located. During the past 20 years, studies in the laboratory and clinic have documented that ARBs, either alone or in combination with drugs of other classes, reduce blood pressure (BP) in hypertensive animals and humans; reduce rates of myocardial infarction (MI), stroke, and progression of renal impairment; and positively impact oth...

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Effect of losartan on human platelet activation

Cited by 62 publications

References 17 publications

Effects of aliskiren, a renin inhibitor, on biomarkers of platelet activity, coagulation and fibrinolysis in subjects with multiple risk factors for vascular disease

Effects of aliskiren, a renin inhibitor, on biomarkers of platelet activity, coagulation and fibrinolysis in subjects with multiple risk factors for vascular disease

Possible pathophysiologic mechanisms supporting the superior stroke protection of angiotensin receptor blockers compared to angiotensin-converting enzyme inhibitors: clinical and experimental evidence

Angiotensin Receptor Blockers: Pharmacology, Efficacy, and Safety

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