Fifteen years of <scp>LIFE</scp> (Losartan Intervention for Endpoint Reduction in Hypertension)—Lessons learned for losartan: An “old dog playing good tricks”

Katsiki, Niki; Tsioufis, Κonstantinos; Ural, Dilek; Volpe, Massimo

doi:10.1111/jch.13325

Cited by 19 publications

(13 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The reduction of a40 proceeded smoothly, yielding b40 in excellent yield. Continuing with our exploration of late‐stage reductions, we used the losartan derivative a41 ; losartan is a medication used to treat high blood‐pressure, in some cases for diabetic kidney disease and hearth failure; a41 was reduced in very good yield. Quinine modification afforded a42 , and its reduction produced the corresponding sulfide b42 as the sole product in excellent yield; quinine is an antimalarial used mainly for infections produced by Plasmodium Falciparum , which is resistant to chloroquine or when other drugs are not available .…”

Section: Resultsmentioning

confidence: 99%

Electrophilic Chlorine from Chlorosulfonium Salts: A Highly Chemoselective Reduction of Sulfoxides

Acosta-Guzmán

Mahecha-Mahecha

Gamba‐Sánchez

2020

Chemistry A European J

View full text Add to dashboard Cite

Herein, we describe a selective late‐stage deoxygenation of sulfoxides based on a novel application of chlorosulfonium salts and demonstrate a new process using these species generated in situ from sulfoxides as the source of electrophilic chlorine. The use of highly nucleophilic 1,3,5‐trimethoxybenzene (TMB) as the reducing agent is described for the first time and applied in the deoxygenation of simple and functionalized sulfoxides. The method is easy to handle, economic, suitable for gram‐scale operations, and readily applied for poly‐functionalized molecules, as demonstrated with more than 45 examples, including commercial medicines and analogues. We also report the results of competition experiments that define the more reactive sulfoxide and we present a mechanistic proposal based on substrate and product observations.

show abstract

Section: Resultsmentioning

confidence: 99%

Electrophilic Chlorine from Chlorosulfonium Salts: A Highly Chemoselective Reduction of Sulfoxides

Acosta-Guzmán

Mahecha-Mahecha

Gamba‐Sánchez

2020

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…The LIFE study and its additional analysis demonstrated the results according to which the presence of LVH and left bundle branch block signs on ECG increases the risk of cardiovascular death by 1,6 times, sudden cardiac death -by 3,4 times and hospital admission rate for heart failure -by 1.7 times [15].…”

Section: Original Researchmentioning

confidence: 97%

Combined influence of diabetes mellitus and obesity on left ventricle remodeling in hypertensive patients

Шелест¹,

Kovalova²,

Шелест³

et al. 2021

ZMJ

View full text Add to dashboard Cite

The aim of the study was to evaluate the effect of type 2 diabetes mellitus (T2DM) and obesity influence on the left ventricular (LV) remodeling peculiarities in hypertensive patients. Materials and methods. In total, 327 patients, aged 38–74 years, were comprehensively examined. The enrolled patients were divided into 4 groups in dependence of the presence of associated disease: the 1st group – n = 87 hypertensive patients with T2DM combined with obesity, the 2nd group – n = 71 hypertensive patient with T2DM and the 3rd group – n = 65 hypertensive patients with obesity; the comparison group consisted of 74 patients with essential hypertension (EH) but without obesity or diabetes. Echocardiography was performed according to the standard method of H. Feigenbaum to estimate the LV parameters. HbA1c was determined by turbidimetric method. Serum glucose levels were determined by ELISA. Results. When comparing the three patient groups with those who had only EH, the most significant influence was found in combined influence of T2DM and obesity on the development of unfavorable type of LV remodeling with values of χ2 = 29.371 and Pearson's contingency coefficient (C) ‒ 0.393 (P < 0.05). The presence of concomitant T2DM without obesity had a significant moderate relationship with the development of unfavorable LV geometry, χ2 = 11.029 and C ‒ 0.266 (P < 0.05), which indicates a much smaller impact on the process compared to the polymorbid effect of T2DM with obesity. Comparison of patients with a combination of EH and obesity with those who had only EH did not show a significant effect of concomitant obesity on the development of unfavorable types of LV geometry with values of χ2 and C: 0.529 and 0.062, respectively (P > 0.05). Conclusions. Essential hypertension with type 2 diabetes mellitus and obesity polymorbidity, but not in combination with type 2 diabetes mellitus or obesity alone, has the most significant association with hypertrophic types of LV remodeling. The co-existence of type 2 diabetes mellitus and obesity in hypertensive patients leads to the development of predominantly LV concentric hypertrophy.

show abstract

“…Perioperative management of ANG II-related medication is debated (21). Reducing ANG II has significant clinical relevance in managing hypertension and heart failure and angiotensin II type 1 receptor (AT 1 R) blockade has been shown to have renoprotective properties (22). Still, it is common clinical practice to discontinue ongoing ANG II-related medication preoperatively to avoid and reduce hypotensive events, which are more prominent in patients with continued treatment (23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

Prevention of hemorrhage-induced renal vasoconstriction and hypoxia by angiotensin II type 1 receptor antagonism in pigs

Franzén

Näslund

Wang

et al. 2021

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Angiotensin II (AngII) is a potent vasoconstrictor and may reduce renal blood flow (RBF), causing renal hypoxia. Hypotensive hemorrhage elevates plasma AngII levels and is associated with increased risk of acute kidney injury. We hypothesized that AngII antagonism prevents renal vasoconstriction and hypoxia caused by hemorrhage. Pigs were anaesthetized, surgically prepared and randomized to intravenous losartan (1.5 mg kg-1 h-1, n=8) or an equal volume of intravenous Ringer's acetate (vehicle-treated, n=8). Hemorrhage was induced by continuous aspiration of blood to reach and sustain mean arterial blood pressure of <50 mmHg for 30 minutes. Plasma AngII levels, hemodynamics and oxygenation were assessed 60 minutes pre-hemorrhage, 30-minutes after the start of hemorrhage and 60 minutes post-hemorrhage. Erythropoietin mRNA was analyzed in cortical and medullary tissue sampled at the end of the experiment. Hypotensive hemorrhage increased plasma AngII levels and decreased RBF and oxygen delivery in both groups. Losartan-treated animals recovered in RBF and oxygen delivery, whereas vehicle-treated animals had persistently reduced RBF and oxygen delivery. In accordance, renal vascular resistance increased over time post hemorrhage in vehicle-treated animals but was unchanged in losartan-treated animals. Renal oxygen extraction rate and cortical erythropoietin mRNA levels increased in the vehicle group but not in the losartan group. In conclusion, AngII antagonism alleviates prolonged renal vasoconstriction and renal hypoxia in a large animal model of hypotensive hemorrhage.

show abstract

Fifteen years of LIFE (Losartan Intervention for Endpoint Reduction in Hypertension)—Lessons learned for losartan: An “old dog playing good tricks”

Cited by 19 publications

References 68 publications

Electrophilic Chlorine from Chlorosulfonium Salts: A Highly Chemoselective Reduction of Sulfoxides

Electrophilic Chlorine from Chlorosulfonium Salts: A Highly Chemoselective Reduction of Sulfoxides

Combined influence of diabetes mellitus and obesity on left ventricle remodeling in hypertensive patients

Prevention of hemorrhage-induced renal vasoconstriction and hypoxia by angiotensin II type 1 receptor antagonism in pigs

Contact Info

Product

Resources

About