New drugs, procedures, and devices for hypertension
Department of Pharmacology, European Georges Pompidou Hospital, Assistance Publique Hôpitaux de Paris, Paris, France. The Lancet
(Impact Factor: 45.22).
08/2012; 380(9841):591-600. DOI: 10.1016/S0140-6736(12)60825-3
Successful treatment of hypertension is difficult despite the availability of several classes of antihypertensive drug, and the value of strategies to combat the effect of adverse lifestyle behaviours on blood pressure. In this paper, we discuss two promising therapeutic alternatives for patients with resistant hypertension: novel drugs, including new pharmacological classes (such as vasopeptidase inhibitors and aldosterone synthase inhibitors) and new molecules from present pharmacological classes with additional properties in blood-pressure or metabolism pathways; and new procedures and devices, including stimulation of arterial baroreceptors and catheter-based renal denervation. Although several pharmacological targets have been discovered with promising preclinical results, the clinical development of novel antihypertensive drugs has been more difficult and less productive than expected. The effectiveness and safety of new devices and procedures should be carefully assessed in patients with resistant hypertension, thus leading to a new era of outcome trials and evidence-based guidelines.
Available from: Masaki Mogi
- "The beneficial effects of inhibition of RAAS on the pathogenesis of cardiovascular diseases may potentially be augmented by enhancement of NP activity (Burnett, 1999; Laurent et al., 2012). However, AT 1 receptor blockade and NEP inhibition increase angiotensin II and decrease angiotensin-(1–7) levels, which could counteract some beneficial effects of LCZ696 associated with NPs (Campbell, 2003). "
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ABSTRACT: Angiotensin II receptor blockers (ARBs) are known to prevent ischemic brain damage after stroke. Natriuretic peptides, which are increased by a neprilysin inhibitor, are also reported to protect against brain damage. Therefore, we investigated the possible protective effect of valsartan (VAL) compared with LCZ696 (VAL+ neprilysin inhibitor; 1:1) after middle cerebral artery (MCA) occlusion. Eight-week-old male C57BL/6J mice were treated with VAL (3mg/kg per day) or LCZ696 (6mg/kg per day) for 2 weeks before MCA occlusion. Blood pressure and heart rate were measured by telemetry. Cerebral blood flow (CBF) was determined by laser-Doppler flowmetry. Ischemic area was evaluated by triphenytetrasodium chloride staining, and oxidative stress was determined by dihydroethidium staining. Blood pressure and heart rate were not significantly different before and after treatment. Pre-treatment with LCZ696 or VAL reduced the ischemic area, and this effect of LCZ696 was more marked than that of VAL pre-treatment. The decrease in CBF in the peripheral region of the ischemic area was significantly attenuated by pre-treatment with LCZ696 or VAL, without any significant effect on CBF in the core region. VAL or LCZ696 pre-treatment significantly decreased the increase of superoxide anion production in the cortex on the ischemic side. However, no significant difference in CBF and superoxide anion production was observed between VAL and LCZ696 pre-treatment. The preventive effect of LCZ696 on ischemic brain damage after stroke was more marked than that of VAL. LCZ696 could be used as a new approach to prevent brain damage after stroke. (246 words).
Copyright © 2015. Published by Elsevier B.V.
European journal of pharmacology 06/2015; 762. DOI:10.1016/j.ejphar.2015.05.059 · 2.53 Impact Factor
Available from: Henrique De Azevedo Futuro Neto
- "The importance of sympathetic nervous system activation in the pathogenesis of hypertension has been demonstrated, and the therapeutic value of sympathetic nervous inhibition in hypertensive patients is already evident and has been widely studied . Ongoing activity of premotor rostral ventrolateral medulla (RVLM) neurons is responsible for the tonic generation of sympathetic vasomotor tone; inhibition of RVLM neurons causes a large decrease in both arterial blood pressure (BP) and sympathetic nervous system activity, while stimulation of this medullary region increases sympathetic vasomotor outflow and BP  . "
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ABSTRACT: The hypothesis that changes in neurotransmission within the rostral ventrolateral medulla (RVLM) are important to maintain the high blood pressure (BP) was tested in Goldblatt one kidney-one clip hypertension model (1K-1C). Male Wistar rats were anesthetized (urethane 1.2 g/kg, i.v.), and the effects of bilateral microinjections into the RVLM of the following drugs were measured in 1K-1C or control groups: glutamate (0.1 mol/L, 100 nL) and its antagonist kynurenic acid (0.02 mol/L, 100 nL), the angiotensin AT1 receptor antagonist candesartan (0.01 mol/L, 100 nL), and the nonselective 5-HT receptor antagonist methiothepin (0.06 mol/L, 100 nL). Experiments in 1K-1C rats were performed 6 weeks after surgery. In anesthetized rats glutamate response was larger in hypertensive than in normotensive rats (H: Δ67 ± 6.5; N: Δ43 ± 3.54 mmHg). In contrast, kynurenic acid microinjection into the RVLM did not cause any change in BP in either group. The blockade of either AT1 or 5-HT receptors within the RVLM decreased BP only in 1K-1C rats. A largest depressor response was caused by 5-HT receptor blockade. The data suggest that 5-HT and AT1 receptors act tonically to drive RVLM in 1K-1C rats, and these actions within RVLM contribute to the pathogenesis of this model of hypertension.
International Journal of Hypertension 01/2014; 2014:723939. DOI:10.1155/2014/723939
Available from: Ismaila Raji
- "All drugs, except where otherwise indicated, were purchased from Sigma Aldrich, SA. ANG I and ANG II which have potential antagonistic effect to that of A. gangetica, were used as negative controls of A. gangetica[6,7,18]. Fresh solutions were made at the beginning of each experiment. "
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ABSTRACT: Asystasia gangentica (A. gangetica) belongs to the family Acanthaceae. It is used to treat hypertension, rheumatism, asthma, diabetes mellitus, and as an anthelmintic in South Africa, India, Cameroun, Nigeria, and Kenya respectively. It has also been reported to inhibit the angiotensin I converting enzyme (ACE) in-vitro. Therefore, the aim of this study is to investigate the in-vivo effect of aqueous leaf extract (ALE) of A. gangetica on the blood pressure (BP) and heart rate (HR) in anaesthetized male spontaneously hypertensive rats (SHR); and to elucidate possible mechanism(s) by which it acts.
The ALE of A. gangetica (10--400 mg/kg), angiotensin I human acetate salt hydrate (ANG I, 3.1--100 mug/kg) and angiotensin II human (ANG II, 3.1--50 mug/kg) were administered intravenously. The BP and HR were measured via a pressure transducer connecting the femoral artery to a Powerlab and a computer for recording.
A. gangetica significantly (p<0.05), and dose-dependently reduced the systolic, diastolic, and mean arterial BP. The significant (p<0.05) reductions in HR were not dose-dependent. Both ANG I and ANG II increased the BP dose-dependently. Co-infusion of A. gangetica (200 mg/kg) with either ANG I or ANG II significantly (p<0.05) suppressed the hypertensive effect of both ANG I and ANG II respectively, and was associated with reductions in HR.
A. gangetica ALE reduced BP and HR in the SHR. The reduction in BP may be a result of actions of the ALE on the ACE, the ANG II receptors and the heart rate.
BMC Complementary and Alternative Medicine 10/2013; 13(1):283. DOI:10.1186/1472-6882-13-283 · 2.02 Impact Factor
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