Angiotensin II constricts mouse iliac arteries: possible mechanism for aortic aneurysms

Gadanec, Laura Kate; McSweeney, Kristen Renee; Kubatka, Peter; Čaprnda, Martin; Gašpar, Ľudovít; Prosecký, Robert; Dragašek, Jozef; Kružliak, Peter; Apostolopoulos, Vasso; Zulli, Anthony

doi:10.1007/s11010-023-04724-0

Cited by 2 publications

(1 citation statement)

References 44 publications

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“…An often-ignored problem inherent to the use of rodent models is the existence of two AT 1 R isoforms, namely AT 1 R subtype A and B [94], the latter of which is predominantly responsible for mediating AngII vasoconstriction responses [95]. However, we [96] and others [95,97] have shown the inability or reduced capacity of AngII to stimulate contraction responses in rodent blood vessels, including the thoracic and abdominal aorta, and carotid and brachiocephalic arteries. This may be explained by reduced sensitivity to AngII, desensitization of AT1R subtypes subsequent to successive AngII exposure and poor expression profiles in blood vessels [98].…”

Section: Animal Model Care and Ethics Approvalmentioning

confidence: 98%

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

Gadanec,

Swiderski,

Apostolopoulos

et al. 2023

IJMS

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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.

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Section: Animal Model Care and Ethics Approvalmentioning

confidence: 98%

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

Gadanec,

Swiderski,

Apostolopoulos

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

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Cellular, Molecular and Clinical Aspects of Aortic Aneurysm—Vascular Physiology and Pathophysiology

Domagała,

Data,

Szyller

et al. 2024

Cells

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A disturbance of the structure of the aortic wall results in the formation of aortic aneurysm, which is characterized by a significant bulge on the vessel surface that may have consequences, such as distention and finally rupture. Abdominal aortic aneurysm (AAA) is a major pathological condition because it affects approximately 8% of elderly men and 1.5% of elderly women. The pathogenesis of AAA involves multiple interlocking mechanisms, including inflammation, immune cell activation, protein degradation and cellular malalignments. The expression of inflammatory factors, such as cytokines and chemokines, induce the infiltration of inflammatory cells into the wall of the aorta, including macrophages, natural killer cells (NK cells) and T and B lymphocytes. Protein degradation occurs with a high expression not only of matrix metalloproteinases (MMPs) but also of neutrophil gelatinase-associated lipocalin (NGAL), interferon gamma (IFN-γ) and chymases. The loss of extracellular matrix (ECM) due to cell apoptosis and phenotype switching reduces tissue density and may contribute to AAA. It is important to consider the key mechanisms of initiating and promoting AAA to achieve better preventative and therapeutic outcomes.

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Angiotensin II constricts mouse iliac arteries: possible mechanism for aortic aneurysms

Cited by 2 publications

References 44 publications

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

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

Cellular, Molecular and Clinical Aspects of Aortic Aneurysm—Vascular Physiology and Pathophysiology

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