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Novel Drugs in the Treatment of Hypertension

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Interventional Therapies for Secondary and Essential Hypertension

Part of the book series: Updates in Hypertension and Cardiovascular Protection ((UHCP))

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Abstract

Pharmacological therapy in combination with lifestyle changes represents the backbone of the therapeutic management of arterial hypertension (HTN) [1]. The recent European guidelines of the European Society of Hypertension and the European Society of Cardiology for the management of HTN recommend with class I and evidence level A the use of diuretics (including thiazides, chlorthalidone, and indapamide), beta-blockers, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARB) for the initiation and maintenance of antihypertensive treatment, either as monotherapy or in some combinations with each other [1]. The impressive prognostic value of blood pressure (BP) lowering in hypertensive patients by using treatment algorithms that are based on the use of these drugs has been demonstrated in multiple trials [1] including the recent Randomized Trial of Intensive versus Standard Blood-Pressure Control (SPRINT) [2]. In addition, further drugs including mineralocorticoid receptor (MR) antagonists, amiloride, and the alpha-1-blocker doxazosin are available for treatment of patients with resistant hypertension [1]. Nevertheless, there is still a need for additional novel BP-lowering drugs, e.g., in the latter patients, in individuals with special conditions (comorbidities), or in patients not responding or tolerating the available drugs. Accordingly, several novel drugs for the treatment of HTN are being currently developed either at the preclinical or clinical stage. They will be summarized in this short overview, and a summary of the compounds and their status of development is given in the Table 10.1.

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Abbreviations

ACE:

Angiotensin-converting enzyme

ACE2:

Angiotensin-converting enzyme 2

Ala:

Alamandine

Ang 1–7:

Angiotensin 1–7

Ang 1–9:

Angiotensin 1–9

Ang II:

Angiotensin II

Ang III:

Angiotensin III

Ang IV:

Angiotensin IV

ANP:

Atrial natriuretic peptide

APA:

Aminopeptidase A

APN:

Aminopeptidase N

ARB:

Angiotensin receptor blockers

ARNI:

Angiotensin receptor–neprilysin inhibitor

AT1:

Angiotensin II type 1

AT2:

Angiotensin II type 2

ATryn:

Recombinant human antithrombin

BNP:

B-type natriuretic peptide

BP:

Blood pressure

C21:

Compound 21

cGMP:

Cyclic guanosine monophosphate

CINOD:

Cyclooxygenase-inhibiting nitric oxide donator

CYP:

Cytochrome P450

DIF:

Digoxin antibody fab

DN:

Diabetic nephropathy

DβH:

Dopamine β-hydroxylase

ECE:

Endothelin-converting enzyme

EDLF:

Endogenous digitalis-like factors

ENaC:

Epithelial sodium channel

EO:

Endogenous ouabain

ET-1:

Endothelin-1

ETA:

Endothelin A

ETB:

Endothelin B

GWAS:

Genome-wide association studies

HF:

Heart failure

HFrEF:

Heart failure with reduced ejection fraction

HP-β-CD:

Hydroxypropyl-β-cyclodextrin

HTN:

Hypertension

IRAP:

Insulin-regulated membrane aminopeptidase/insulin-responsive aminopeptidase

MHS:

Milan hypertensive

MR:

Mineralocorticoid receptor

NAT2:

N-acetyltransferase 2

NEP:

Neutral endopeptidase 24.11

NHE:

Na+/H+ exchangers

NHE3:

NHE isoform 3

NO:

Nitric oxide

NPR:

Natriuretic peptide receptor

RAAS:

Renin–angiotensin–aldosterone system

rhACE2:

Recombinant human angiotensin-converting enzyme

sEH:

Soluble epoxide hydrolase

SGC:

Soluble guanylate cyclase

SHR:

Spontaneously hypertensive rats

VIP:

Vasoactive intestinal polypeptide

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Authors and Affiliations

  1. Department of Clinical Pharmacology and Toxicology, Institut für Klinische Pharmakologie und Toxikologie, Charité – Universitätsmedizin Berlin, Charitéplatz 1, Berlin, 10117, Germany

    Reinhold Kreutz & Engi Abdel-Hady Algharably

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  1. Reinhold Kreutz
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  2. Engi Abdel-Hady Algharably
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Correspondence to Reinhold Kreutz .

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Editors and Affiliations

  1. First Cardiology Clinic, National and Kapodistrian University of Athens, Athens, Greece

    Costas Tsioufis

  2. Department of Nephrology and Hypertension, University Hospital Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany

    Roland E. Schmieder

  3. IRCCS Istituto Auxologico Italiano, University Milano-Bicocca, Milano Monza, Italy

    Giuseppe Mancia

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Kreutz, R., Abdel-Hady Algharably, E. (2016). Novel Drugs in the Treatment of Hypertension. In: Tsioufis, C., Schmieder, R., Mancia, G. (eds) Interventional Therapies for Secondary and Essential Hypertension. Updates in Hypertension and Cardiovascular Protection. Springer, Cham. https://doi.org/10.1007/978-3-319-34141-5_10

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  • DOI: https://doi.org/10.1007/978-3-319-34141-5_10

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