Therapeutic perspectives in hypertension: novel means for renin-angiotensin-aldosterone system modulation and emerging device-based approaches

Abstract

The conventional antihypertensive therapies including renin–angiotensin–aldosterone system antagonists (converting enzyme inhibitors, receptor blockers, renin inhibitors, and mineralocorticoid receptor blockers), diuretics, β-blockers, and calcium channel blockers are variably successful in achieving the challenging target blood pressure values in hypertensive patients. Difficult to treat hypertension is still a commonly observed problem world-wide. A number of drugs are considered to be used as novel therapies for hypertension. Renalase supplementation, vasopeptidase inhibitors, endothelin antagonists, and especially aldosterone antagonists (aldosterone synthase inhibitors and novel selective mineralocorticoid receptor blockers) are considered an option in resistant hypertension. In addition, the aldosterone antagonists as well as (pro)renin receptor blockers or AT2 receptor agonists might attenuate end-organ damage. This array of medications has now been complemented by a number of new approaches of non-pharmacological strategies including vaccination, genomic interference, controlled breathing, baroreflex activation, and probably most successfully renal denervation techniques. However, the progress on innovative therapies seems to be slow and the problem of resistant hypertension and proper blood pressure control appears to be still persisting. Therefore the regimens of currently available drugs are being fine-tuned, resulting in the establishment of several novel fixed-dose combinations including triple combinations with the aim to facilitate proper blood pressure control. It remains an exciting question which approach will confer the best blood pressure control and risk reduction in this tricky disease.

Direct Angiotensin II Type 2 Receptor Stimulation in N ω -Nitro- l -Arginine-Methyl Ester–Induced Hypertension

“…We have compared the effects of compound 21 to olmesartan at a high 10-mg/kg antihypertensive dose that completely prevented hypertension. AT 1 R antagonists currently not only belong to the gold standard therapies for hypertension and cardioprotection at various stages of the cardiovascular continuum 5,6 but have shown the highest potential for preventing and reducing PWV in hypertension. [7][8][9][10] Also in our study olmesartan completely prevented PWV increase and aortic wall thickening.…”

“…The angiotensin II type 1 receptor (AT 1 R) antagonists, together with angiotensin-converting enzyme inhibitors, belong to the gold standard cardioprotective therapies. 5,6 In a study on 113 hypertensives, 2-to 3-year treatment with candesartan produced a larger reduction of brachial-ankle PWV than treatment with amlodipine, 7 and eprosartan in contrast to atenolol effectively reduced PWV despite the same level of blood pressure (BP) control in subjects with never-treated hypertension. 8 Anti-AT 1 R-based therapy was superior over treatment not containing an AT 1 R antagonist in preventing PWV increase in patients with essential hypertension, 9 and highdose valsartan treatment achieved more pronounced brachialankle PWV reduction than low-dose valsartanϩdiuretic despite a similar level of BP reduction in patients with morning hypertension.…”

Effects of the T/L-type Calcium Channel Blocker Benidipine on Albuminuria and Plasma Aldosterone Concentration

“…As a result, the expression of aldosterone synthase enzyme at the adrenal cortex is inhibited. 16) Akizuki, et al conducted an in vitro study using human adrenal cortex cells (NCI-H295R cells) and 10 minutes after the addition of various CCBs, 10 mM KCl was added to induce the production of aldosterone, and the aldosterone concentration in the culture media was measured 24 hours later. Consequently, the L-type CCB nifedipine did not inhibit the secretion of aldosterone while benidipine inhibited aldosterone secretion in a dosedependent manner.…”

Is Renalase a Novel Player in Catecholaminergic Signaling? The Mystery of the Catalytic Activity of an Intriguing New Flavoenzyme

“…Renalase has been proposed as a drug for replacement therapy in end stage renal disease [12,17,59,70,72], as early biomarker of acute kidney ischemia [10] and essential hypertension [8], as well as prognostic factor for stroke [27,45], and even as possible target for the therapy of psychiatric disorders caused by altered catecholaminergic signaling in the central nervous system [19]. Obviously, development of effective tools for pharmacological intervention requires the mechanism of renalase action to be known at the molecular level.…”