scholarly journals RAAS blockade and COVID‐19: Mechanistic Modeling of mas and AT1 Receptor Occupancy as Indicators of Pro‐ and Anti‐Inflammatory Balance

2021 ◽  
Author(s):  
Karen Melissa Hallow ◽  
Ishaan Dave
Keyword(s):  
Receptor Occupancy ◽  
At1 Receptor ◽  
Mechanistic Modeling ◽  
Raas Blockade ◽  
Anti Inflammatory

scholarly journals Improvement of endothelial dysfunction in experimental heart failure by chronic RAAS-blockade: ACE-inhibition or AT1-receptor blockade?

2001 ◽  
Vol 2 (1_suppl) ◽  
pp. S64-S69 ◽  
Author(s):  
Lodewijk J Wagenaar ◽  
Hendrik Buikema ◽  
Yigal M Pinto ◽  
Wiek H van Gilst
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Heart Failure ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Candesartan Cilexetil ◽  
Ace Inhibition ◽  
At1 Receptor ◽  
Converting Enzyme Inhibitors ◽  
Raas Blockade

Chronic heart failure (CHF) is associated with endothelial dysfunction. Activation of the renin-angiotensin-aldosterone system (RAAS) is believed to be important in the deterioration of endothelial dysfunction in CHF through stimulation of oxidative stress. Whereas angiotensin-converting enzyme inhibitors (ACE-I) improve endothelial function in CHF, the effects of angiotensin II AT1-receptor blockers (ARB) are less well established. Therefore we compared the effects of the ACE-I lisinopril vs. the ARB candesartan on endothelial dysfunction in a rat model of CHF. CHF was induced by myocardial infarction (MI) after coronary ligation. Two weeks after MI, daily treatment with lisinopril (2 mg/kg) or candesartan cilexetil (1.5 mg/kg) was started. After 13 weeks, rats were sacrificed and endothelial function was determined by measuring acetylcholine (ACh)-induced vasodilation in aortic rings, with selective presence of the nitric oxide synthase (NOS)-inhibitor NG-monomethyl-L-arginine (L-NMMA) to determine the contribution of nitric oxide (NO). ACh-induced vasodilation was attenuated in untreated MI (-50%) compared with control rats. This was in part due to an impaired contribution of NO (-49%). Lisinopril and candesartan cilexetil fully normalised ACh-induced dilation, including the part mediated by NO. Chronic RAAS-blockade with lisinopril and candesartan cilexetil normalised endothelial function in CHF in a comparable way. The effect of both treatments included the increase of the NO-mediated dilation, further indicating the important role of oxidative stress in the relationship between the RAAS and endothelial dysfunction in CHF.

scholarly journals Polyfunctional antiallergic potencies of Д-antihistamine levocetirizine

2014 ◽  
Vol 11 (2) ◽  
pp. 11-24
Author(s):  
I S Gushchin
Keyword(s):  
Public Health ◽  
Allergic Rhinitis ◽  
Public Health Problem ◽  
Receptor Occupancy ◽  
Allergic Diseases ◽  
Therapeutic Benefit ◽  
Efficacy And Safety ◽  
Adults And Children ◽  
Anti Inflammatory

The burden of allergic diseases worldwide is such that it represents a serious public health problem that attracts considerable efforts to identify effective and safe therapies. Antihistamines are an important part of the therapeutic options for allergic diseases. Levocetirizine is the R-enantiomer of cetirizine with pharmacokinetically and pharmacodynamically favourable characteristics. It is a potent inverse agonist of H 1-receptors with anti-inflammatory/anti-allergic properties. It appears to have grater in vivo H 1-receptor occupancy comparatively with other 2 nd generation H 1-antihistamines. This may confer an advantageous efficacy and safety profile. clinical trials indicate that it is safe and effective for the treatment of allergic rhinitis, chronic urticaria and some other allergic conditions in adults and children with a minimal number of untoward reactions. It is also becoming clearer that, in addition to its being a potent antihistamine, levocetirizine has several anti-inflammatory/anti-allergic effects that are observed at clinically relevant concentrations that may enhance its therapeutic benefit.

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