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
Source: PubMed

ABSTRACT 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.

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    • "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 [1]. 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 [2] [3]. "
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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.
    01/2014; 2014:723939. DOI:10.1155/2014/723939
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    • "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 · 1.88 Impact Factor
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    • "Medications currently undergoing preclinical trials for antihypertensive treatment are not presumed to have predominant sympathetic autonomic effects.68 At this point, drug-resistant hypertension is being studied by means of radiofrequency69 or cryoablation70 of nerves surrounding the renal arteries, testing the hypothesis that interruption of pathological reflexes with relaxation of stiff vessels, plus excretion of excess salt, would forestall cardiovascular events by restoring homeostatic relationships. "
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    ABSTRACT: Research in resistant hypertension has again focused on autonomic nervous system denervation - 50 years after it had been stopped due to postural hypotension and availability of newer drugs. These (ganglionic blockers) drugs have all been similarly stopped, due to postural hypotension and yet newer antihypertensive agents. Recent demonstration of the feasibility of limited regional transcatheter sympathetic denervation has excited clinicians due to potential therapeutic implications. Standard use of ambulatory blood pressure recording equipment may alter our understanding of the diagnosis, potential treatment strategies, and health care outcomes - when faced with patients whose office blood pressure remains in the hypertensive range - while under treatment with three antihypertensive drugs at the highest tolerable doses, plus a diuretic. We review herein clinical relationships between autonomic function, resistant hypertension, current treatment strategies, and reflect upon the possibility of changes in our approach to resistant hypertension.
    International Journal of Nephrology and Renovascular Disease 08/2013; 6:149-160. DOI:10.2147/IJNRD.S40897
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