Existence of Quantum Pharmacology in Sartans: Evidence in Isolated Rabbit Iliac Arteries.

Quantum pharmacology introduces theoretical models to describe the possibility of ultra-high dilutions to produce biological effects, which may help to explain the placebo effect observed in hypertensive clinical trials. To determine this within physiology and to evaluate novel ARBs, we tested the ability of known angiotensin II receptor blockers (ARBs) (candesartan and telmisartan) used to treat hypertension and other cardiovascular diseases, as well as novel ARBs (benzimidazole-N-biphenyl tetrazole (ACC519T), benzimidazole-bis-N,N'-biphenyl tetrazole (ACC519T(2)) and 4-butyl-N,N0-bis[[20-2Htetrazol-5-yl)biphenyl-4-yl]methyl)imidazolium bromide (BV6(K+)2), and nirmatrelvir (the active ingredient in Paxlovid) to modulate vascular contraction in iliac rings from healthy male New Zealand White rabbits in responses to various vasopressors (angiotensin A, angiotensin II and phenylephrine). Additionally, the hemodynamic effect of ACC519T and telmisartan on mean arterial pressure in conscious rabbits was determined, while the ex vivo ability of BV6(K+)2 to activate angiotensin-converting enzyme-2 (ACE2) was also investigated. We show that commercially available and novel ARBs can modulate contraction responses at ultra-high dilutions to different vasopressors. ACC519T produced a dose-dependent reduction in rabbit mean arterial pressure while BV6(K+)2 significantly increased ACE2 metabolism. The ability of ARBs to inhibit contraction responses even at ultra-low concentrations provides evidence of the existence of quantum pharmacology. Furthermore, the ability of ACC519T and BV6(K+)2 to modulate blood pressure and ACE2 activity, respectively, indicates their therapeutic potential against hypertension.

Combination of Taurine and Black Pepper Extract as a Treatment for Cardiovascular and Coronary Artery Diseases.

The shift in modern dietary regimens to "Western style" and sedentary lifestyles are believed to be partly responsible for the increase in the global burden of cardiovascular diseases. Natural products have been used throughout human history as treatments for a plethora of pathological conditions. Taurine and, more recently, black pepper have gained attention for their beneficial health effects while remaining non-toxic even when ingested in excess. Taurine, black pepper, and the major terpene constituents found in black pepper (i.e., ß-caryophyllene; α-pinene; ß-pinene; α-humulene; limonene; and sabinene) that are present in PhytoCann BP® have been shown to have cardioprotective effects based on anti-inflammatory, antioxidative, anti-hypertensive and anti-atherosclerotic mechanisms. This comprehensive review of the literature focuses on determining whether the combination of taurine and black pepper extract is an effective natural treatment for reducing cardiovascular diseases risk factors (i.e., hypertension and hyperhomocysteinemia) and for driving anti-inflammatory, antioxidative and anti-atherosclerotic mechanisms to combat coronary artery disease, heart failure, myocardial infarction, and atherosclerotic disease.

Role of Angiotensin II in Cardiovascular Diseases: Introducing Bisartans as a Novel Therapy for Coronavirus 2019.

Cardiovascular diseases (CVDs) are the main contributors to global morbidity and mortality. Major pathogenic phenotypes of CVDs include the development of endothelial dysfunction, oxidative stress, and hyper-inflammatory responses. These phenotypes have been found to overlap with the pathophysiological complications of coronavirus disease 2019 (COVID-19). CVDs have been identified as major risk factors for severe and fatal COVID-19 states. The renin-angiotensin system (RAS) is an important regulatory system in cardiovascular homeostasis. However, its dysregulation is observed in CVDs, where upregulation of angiotensin type 1 receptor (AT1R) signaling via angiotensin II (AngII) leads to the AngII-dependent pathogenic development of CVDs. Additionally, the interaction between the spike protein of severe acute respiratory syndrome coronavirus 2 with angiotensin-converting enzyme 2 leads to the downregulation of the latter, resulting in the dysregulation of the RAS. This dysregulation favors AngII/AT1R toxic signaling pathways, providing a mechanical link between cardiovascular pathology and COVID-19. Therefore, inhibiting AngII/AT1R signaling through angiotensin receptor blockers (ARBs) has been indicated as a promising therapeutic approach to the treatment of COVID-19. Herein, we review the role of AngII in CVDs and its upregulation in COVID-19. We also provide a future direction for the potential implication of a novel class of ARBs called bisartans, which are speculated to contain multifunctional targeting towards COVID-19.