scholarly journals Suppression of Aldosterone Synthesis and Secretion by Channel Antagonists

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Keiichi Ikeda ◽  
Tsuyoshi Isaka ◽  
Kouki Fujioka ◽  
Yoshinobu Manome ◽  
Katsuyoshi Tojo
Keyword(s):  
Angiotensin Ii ◽  
Enzyme Inhibitors ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Channel Blockers ◽  
Converting Enzyme Inhibitors ◽  
Renin Angiotensin ◽  
Aldosterone Production ◽  
Ras Inhibitors

Aldosterone, a specific mineralocorticoid receptor (MR) agonist and a key player in the development of hypertension, is synthesized as a final product of renin-angiotensin-aldosterone system. Hypertension can be generally treated by negating the effects of angiotensin II through the use of angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin II type 1 receptor antagonists (ARBs). However, the efficacy of angiotensin II blockade by such drugs is sometimes diminished by the so-called “aldosterone breakthrough” effect, by which ACE-Is or ARBs (renin-angiotensin system (RAS) inhibitors) gradually lose their effectiveness against hypertension due to the overproduction of aldosterone, known as primary aldosteronism. Although MR antagonists are used to antagonize the effects of aldosterone, these drugs may, however, give rise to life-threatening adverse actions, such as hyperkalemia, particularly when used in conjunction with RAS inhibitors. Recently, several groups have reported that some dihydropyridine Ca2+channel blockers (CCBs) have inhibitory actions on aldosterone production inin vitroand in the clinical setting. Therefore, the use of such dihydropyridine CCBs to treat aldosterone-related hypertension may prove beneficial to circumvent such therapeutic problems. In this paper, we discuss the mechanism of action of CCBs on aldosterone production and clinical perspectives for CCB use to inhibit MR activity in hypertensive patients.

scholarly journals Controversial Roles of the Renin Angiotensin System and Its Modulators During the COVID-19 Pandemic

2021 ◽  
Vol 12 ◽  
Author(s):  
Simon B. Gressens ◽  
Georges Leftheriotis ◽  
Jean-Claude Dussaule ◽  
Martin Flamant ◽  
Bernard I. Levy ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Enzyme Inhibitors ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Renin Angiotensin ◽  
The Impact

Since December 2019, the coronavirus 2019 (COVID-19) pandemic has rapidly spread and overwhelmed healthcare systems worldwide, urging physicians to understand how to manage this novel infection. Early in the pandemic, more severe forms of COVID-19 have been observed in patients with cardiovascular comorbidities, who are often treated with renin-angiotensin aldosterone system (RAAS)-blockers, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), but whether these are indeed independent risk factors is unknown. The cellular receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the membrane-bound angiotensin converting enzyme 2 (ACE2), as for SARS-CoV(-1). Experimental data suggest that expression of ACE2 may be increased by RAAS-blockers, raising concerns that these drugs may facilitate viral cell entry. On the other hand, ACE2 is a key counter-regulator of the RAAS, by degrading angiotensin II into angiotensin (1-7), and may thereby mediate beneficial effects in COVID-19. These considerations have raised concerns about the management of these drugs, and early comments shed vivid controversy among physicians. This review will describe the homeostatic balance between ACE-angiotensin II and ACE2-angiotensin (1-7) and summarize the pathophysiological rationale underlying the debated role of the RAAS and its modulators in the context of the pandemic. In addition, we will review available evidence investigating the impact of RAAS blockers on the course and prognosis of COVID-19 and discuss why retrospective observational studies should be interpreted with caution. These considerations highlight the importance of solid evidence-based data in order to guide physicians in the management of RAAS-interfering drugs in the general population as well as in patients with more or less severe forms of SARS-CoV-2 infection.

scholarly journals The Dilemma of Dual Renin-Angiotensin System Blockade in Chronic Kidney Disease: Why Beneficial in Animal Experiments But Not in the Clinic?

2017 ◽  
pp. 181-192 ◽  
Author(s):  
V. ČERTÍKOVÁ CHÁBOVÁ ◽  
L. ČERVENKA
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Clinical Studies ◽  
Enzyme Inhibitors ◽  
Animal Experiments ◽  
Renin Angiotensin System ◽  
Dual Therapy ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme Inhibitors ◽  
Renin Angiotensin

Drugs interfering with the renin-angiotensin-aldosterone system (RAAS) improved the prognosis in patients with hypertension, heart failure, diabetes and chronic kidney disease. However, combining different drugs brought no further benefit while increasing the risk of hyperkalemia, hypotension and acute renal failure. This was so with combining angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptors type 1 antagonists (ARB). Dissimilarly, in animal disease models this dual therapy proved clearly superior to single drug treatment and became the optimal standard regime for comparison with other treatments. This review analyzes the causes of the discrepancy of effects of the dual therapy between animal experiments versus clinical studies, and is focused on the outcomes in chronic kidney disease. Discussed is the role of species differences in RAAS, of the variability of the disease features in humans versus relative stability in animals, of the genetic uniformity in the animals but not in humans, and of the biased publication habits of experimental versus clinical studies. We attempt to understand the causes and reconcile the discordant findings and suggest to what extent dual RAAS inhibition should be continued in animal experiments and why its application in the clinics should be limited to strictly selected groups of patients.

scholarly journals Angiotensin II and COVID-19. Secrets of interactions

2020 ◽  
Vol 25 (4) ◽  
pp. 3861 ◽  
Author(s):  
A. O. Konradi ◽  
A. O. Nedoshivin
Keyword(s):  
Angiotensin Ii ◽  
Enzyme Inhibitors ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Current Data ◽  
Angiotensin Ii Receptor ◽  
Converting Enzyme Inhibitors ◽  
Receptor Blockers ◽  
Relationship Of ◽  
The Relationship

The article describes current data on the relationship of renin-angiotensin system and related drugs with the risk of COVID-19 infection and its outcomes. Analysis of the latest publications did not reveal association of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with any risk of an unfavorable outcomes, and there was no data for withdrawal of these drugs.

Renin-Angiotensin-Aldosterone System and Migraine: A Systematic Review of Human Studies

2020 ◽  
Vol 27 (6) ◽  
pp. 512-519 ◽  
Author(s):  
Karina Lúcia Moreira Sassi ◽  
Laís Bhering Martins ◽  
Aline Silva de Miranda ◽  
Antonio Lucio Teixeira
Keyword(s):  
Systematic Review ◽  
Enzyme Inhibitors ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Migraine Treatment ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
At1 Receptor Antagonists

Migraine is a common neurologic condition marked by recurrent episodes of headache. Its pathophysiology is highly complex involving neuronal, inflammatory and vascular mechanisms. The Renin-Angiotensin System (RAS) can modulate all these mechanism, being a potential pharmacological target for migraine treatment. We carried out a systematic review of the studies evaluating the involvement of RAS in patients with migraine. There is evidence from genetic studies exploring the relation between migraine and RAS-related genes and from clinical trials evaluating the efficacy of Angiotensin II Type 1 (AT1) receptor antagonists and angiotensin converting enzyme inhibitors in migraine prophylaxis. RAS seems to play a role in the pathophysiology of migraine, but more direct evidence is still missing.

scholarly journals Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: potential allies in the COVID-19 pandemic instead of a threat?

2021 ◽  
Vol 135 (8) ◽  
pp. 1009-1014
Author(s):  
Fedor Simko ◽  
Tomas Baka
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Enzyme Inhibitors ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme ◽  
Angiotensin Ii Receptor ◽  
Converting Enzyme Inhibitors ◽  
Ras Pathway ◽  
Receptor Blockers ◽  
Ras Inhibitors

Abstract Angiotensin-converting enzyme 2 (ACE2) is the leading player of the protective renin–angiotensin system (RAS) pathway but also the entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RAS inhibitors seemed to interfere with the ACE2 receptor, and their safety was addressed in COVID-19 patients. Pedrosa et al. (Clin. Sci. (Lond.) (2021), 135, 465–481) showed in rats that captopril and candesartan up-regulated ACE2 expression and the protective RAS pathway in lung tissue. In culture of pneumocytes, the captopril/candesartan-induced ACE2 up-regulation was associated with inhibition of ADAM17 activity, counterbalancing increased ACE2 expression, which was associated with reduced SARS-CoV-2 spike protein entry. If confirmed in humans, these results could become the pathophysiological background for justifying RAS inhibitors as cornerstone cardiovascular protectives even during COVID-19 pandemic.

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