The Evolution of Renin-Angiotensin Blockade: Angiotensin-Converting Enzyme Inhibitors as the Starting Point

Sica, Domenic A.

doi:10.1007/s11906-010-0091-9

Cited by 17 publications

(4 citation statements)

References 53 publications

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“…Recently, it has been suggested that there may be an overreliance on the Ang II model considering that the model is not reflective of primary (essential) hypertension, which accounts for the majority of hypertension in humans (Galis et al, 2013 ). While the Ang II infusion model is most reflective of secondary forms of hypertension, it should be noted that a major target of antihypertensive therapy in essential hypertension in humans has been directed toward limiting Ang II signaling (e.g., ACE inhibitors and angiotensin receptor blockers) (Sica, 2010 ; Hanselin et al, 2011 ). Thus, the Ang II infusion model clearly has direct relevance to human hypertension irrespective of etiology.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II-induced endothelial dysfunction is temporally linked with increases in interleukin-6 and vascular macrophage accumulation

Gomolak

Didion

2014

Front. Physiol.

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Angiotensin II (Ang II) is associated with vascular hypertrophy, endothelial dysfunction and activation of a number of inflammatory molecules, however the linear events involved in the development of hypertension and endothelial dysfunction produced in response to Ang II are not well defined. The goal of this study was to examine the dose- and temporal-dependent development of endothelial dysfunction in response to Ang II. Blood pressure and responses of carotid arteries were examined in control (C57Bl/6) mice and in mice infused with 50, 100, 200, 400, or 1000 ng/kg/min Ang II for either 14 or 28 Days. Infusion of Ang II was associated with graded and marked increases in systolic blood pressure and plasma Ang II concentrations. While low doses of Ang II (i.e., 50 and 100 ng/kg/min) had little to no effect on blood pressure or endothelial function, high doses of Ang II (e.g., 1000 ng/kg/min) were associated with large increases in arterial pressure and marked impairment of endothelial function. In contrast, intermediate doses of Ang II (200 and 400 ng/kg/min) while initially having no effect on systolic blood pressure were associated with significant increases in pressure over time. Despite increasing blood pressure, 200 ng/kg/min had no effect on endothelial function, whereas 400 ng/kg/min produced modest impairment on Day 14 and marked impairment of endothelial function on Day 28. The degree of endothelial dysfunction produced by 400 and 1000 ng/kg/min Ang II was reflective of parallel increases in plasma IL-6 levels and vascular macrophage content, suggesting that increases in arterial blood pressure precede the development of endothelial dysfunction. These findings are important as they demonstrate that along with increases in arterial pressure that increases in IL-6 and vascular macrophage accumulation correlate with the impairment of endothelial function produced by Ang II.

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Section: Introductionmentioning

confidence: 99%

Angiotensin II-induced endothelial dysfunction is temporally linked with increases in interleukin-6 and vascular macrophage accumulation

Gomolak

Didion

2014

Front. Physiol.

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“…to treat renal fibrosis in the clinic, but efforts have been made to intervene in the primary disease (Li et al 2018). The main clinical treatment for most forms of kidney disease is angiotensin inhibition (Sica 2010). Therefore, it is urgent to develop novel drugs that can treat or delay renal fibrosis.…”

Section: Aip Inhibits Emt Progression In Vivo and In Vitromentioning

confidence: 99%

The CaMKII Inhibitory Peptide AIP Alleviates Renal Fibrosis Through the TGF-β/Smad and RAF/ERK Pathways

Feng

Zhang

Yang

et al. 2023

J Pharmacol Exp Ther

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CaMKII -Calcium (Ca2+)/calmodulin (CaM)-dependent protein kinase II CKD -chronic kidney disease Col I -Collagen I ECM -extracellular matrix EMT -epithelial-to-mesenchymal transformation ERK -extracellular regulated protein kinases ESRD -end-stage renal disease FBS -fetal bovine serum FMT -fibroblast-to-myofibroblast transformation FN -Fibronectin GAPDH -glyceraldehyde-3-phosphate dehydrogenase MAPK -mitogen-activated protein kinase MMP2 -matrix metalloproteinase 2 PKD -polycystic kidney disease ROS -Reactive oxygen species Scr -serum creatinine TGF-β1 -transforming growth factor-β1 UUO -unilateral ureteral obstruction Vim -Vimentin α-SMA -α-smooth muscle actin e) Recommended section: 1) Cellular and Molecular This article has not been copyedited and formatted. The final version may differ from this version.

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“…Oral ACE inhibitors, the oldest category of RAAS inhibitor, were commercially released over thirty years ago in the early 1980s, over a decade before the first ARBs became available 5 . The introduction of ACE inhibitors heralded major changes in the way hypertension and cardiovascular disease were treated.…”

Section: Introductionmentioning

confidence: 99%

RAAS inhibition and mortality in hypertension

Ferrari

2013

Global Cardiology Science and Practice

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The renin-angiotensin-aldosterone system (RAAS) regulates the body's hemodynamic equilibrium, circulating volume, and electrolyte balance, and is a key therapeutic target in hypertension, the world's leading cause of premature mortality. Hypertensive disorders are strongly linked with an overactive RAAS, and RAAS inhibitors, like angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), are routinely used to treat high blood pressure (BP). BP reduction is one of the main goals of current European hypertension guidelines. Oral ACE inhibitors, the oldest category of RAAS inhibitor, were commercially released over 30 years ago in the early 1980s, over a decade before the first ARBs became available. The introduction of ACE inhibitors heralded major changes in the way hypertension and cardiovascular disease were treated. Although the decision of the medical community to replace older ACE inhibitors with more modern ARBs in the 1990s was debatable, it did nevertheless allow scientists to learn more about the angiotensin receptors involved in RAAS stimulation. This and much else of value have been discovered since RAAS inhibitors first became available, but some surprising gaps in our knowledge exist. Until recently, the effect of RAAS inhibition on mortality in hypertension was unknown. This question was recently addressed by a meta-analysis of randomized controlled trials in populations who received contemporary antihypertensive medication. The results of this meta-analysis have helped elucidate the long-term consequences of treatment with RAAS inhibitors on mortality in hypertension. This article will consider the differences between RAAS inhibitors in terms of pharmacological and clinical effects and analyze the impact of the main types of RAAS inhibitor, ACE inhibitors and ARBs, on mortality reduction in hypertensive patients with reference to this latest meta-analysis.

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The Evolution of Renin-Angiotensin Blockade: Angiotensin-Converting Enzyme Inhibitors as the Starting Point

Cited by 17 publications

References 53 publications

Angiotensin II-induced endothelial dysfunction is temporally linked with increases in interleukin-6 and vascular macrophage accumulation

Angiotensin II-induced endothelial dysfunction is temporally linked with increases in interleukin-6 and vascular macrophage accumulation

The CaMKII Inhibitory Peptide AIP Alleviates Renal Fibrosis Through the TGF-β/Smad and RAF/ERK Pathways

RAAS inhibition and mortality in hypertension

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