Platelet Aggregability in Patients with Hypertension Treated with Angiotensin II Type 1 Receptor Blockers
Cardiovascular events associated with hypertension often involve thrombosis. Increased platelet activity is one of the risk factors of cardiovascular diseases. Antithrombotic properties of antihypertensive agents are not fully characterized. Angiotensin II type 1 receptor blockers (ARBs) are widely used for the treatment of hypertension. Some ARBs can provoke antiaggregatory effects on platelets in vitro. Whether ARBs can inhibit platelet aggregation was tested in hypertensive patients in vivo.
Platelet aggregation was assessed by the highly sensitive particle counting method using laser-light scattering.
Large platelet aggregation induced by adenosine diphosphate (ADP, 3 microM) was 2.6+/-0.4 (x10(7)) (SE) in hypertensive patients treated with losartan (72+/-3 years old, n=10) while it was 3.9+/-0.6 in hypertensive patients treated with candesartan (70+/-5 years old, n=6; p=0.056). Large platelet aggregation induced by thromboxane A2 receptor agonist, U46619 (10 microM), was 2.8+/-0.5 (x10(7)) in hypertensive patients treated with losartan while it was 5.1+/-0.9 in hypertensive patients treated with candesartan (p=0.033). Clinical characteristics including the control of blood pressure did not differ between the two groups (losartan 136+/-5/73+/-3 mmHg vs. candesartan 135+/-4/76+/-5).
Thus, losartan may have the possibility to inhibit platelet activation in patients with hypertension independent of blood pressure reduction. Antiaggregatory properties may be independent of angiotensin II type 1 receptor or of antihypertensive actions. The favorable effects of losartan on reduction of adverse cardiovascular events among hypertensive patients may be at least partly mediated by inhibition of platelet activation.
Available from: PubMed Central
- "In humans, losartan and irbesartan have demonstrated this effect, while at higher doses, valsartan and telmisartan have inhibited platelet aggregation.24–26 Candesartan does not appear to influence platelet aggregation.27 In the usual therapeutic dosing range, losartan has been shown to be effective. "
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ABSTRACT: Losartan, the first AT1 receptor blocker (ARB), was FDA approved 15 years ago. During those years, researchers and clinicians have developed a growing base of knowledge on the benefits of losartan, particularly for hypertension and renal disease. These benefits include decreasing proteinuria, slowing the progression of diabetic nephropathy, controlling hypertension, and decreasing stroke risk in patients with left ventricular hypertrophy. Although many of the benefits of losartan represent a class effect for ARBs, losartan has pharmacokinetic and pharmacodynamic characteristics and effects that are unique and are not a class effect. For example, a shorter duration of action is seen with this first ARB compared with other more recently approved ARBs. Losartan also has a uricosuric effect not seen in other ARBs and attenuates platelet aggregation, which is not seen or is seen to a lesser extent with the other ARBs. This review presents the physiological effects of losartan on the kidney and discusses relevant clinical outcomes.
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ABSTRACT: Platelets play an important role in the development of thrombosis, atherosclerosis, hypertension, heart attack and stroke. As a result, pharmacologic interventions that influence platelet functions, such as adhesion, aggregation and the release of different factors, are considered useful for the prevention and treatment of cardiovascular disease. Although classical anti-platelet agents have proven beneficial effects for the treatment of some specific cardiovascular diseases, there are limitations for their use as these drugs target platelet function directly. In contrast, newly developed anti-platelet agents have broad applications for the treatment of cardiovascular disease as they not only influence platelet function but are also considered to affect cardiac and vascular smooth muscle cell functions. Natural food products and nutraceutical agents also appear to modify cardiovascular abnormalities by affecting various platelet functions; however, the mechanisms of their actions remain to be investigated. Accordingly, this article is focused to discuss emerging pharmacologic, nutritional and nutraceutical interventions that may influence the prevention or progression of a broad range of cardiovascular diseases.
Available from: hipertensionmicardis.com
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ABSTRACT: Because all clinically approved angiotensin-receptor blockers (ARBs) have good safety profiles and share the ability to block angiotensin II type 1 (AT1) receptors and reduce blood pressure, it is tempting to assume that all ARBs will yield equivalent degrees of cardiovascular protection. However, such a belief depends on the tacit assumption that with appropriate dosing, all ARBs will also share the same ability to counteract other pathogenetic determinants of cardiovascular disease beyond those involving the renin-angiotensin system. Accumulating evidence from multiple laboratories has shown that this assumption is incorrect and indicates that some ARBs are characterized by an unusual ability to affect potential mechanisms of cardiovascular disease involving more than just the renin-angiotensin system. Ultimately, large-scale clinical trials will be required to better understand the clinical importance of the mechanistic effects of ARBs that involve more than just inhibition of the renin-angiotensin system. Meanwhile, given the many functional differences among ARBs that are not mediated by AT1 receptor blockade, the effects of any particular ARB on cardiovascular outcomes should not be assumed to apply equally to all ARBs let alone to other drugs that inhibit the renin-angiotensin system through different mechanisms.
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