Physiological effects of a biased Angiotensin II type 1 receptor agoniston blood pressure and cerebral blood flow - Université de Lorraine Access content directly
Poster Communications Year : 2023

Physiological effects of a biased Angiotensin II type 1 receptor agoniston blood pressure and cerebral blood flow

Abstract

During ischemic stroke, AngII-mediated vasoconstriction via the AT1 receptor (AT1R) is deleterious as it reduces cerebral blood flow (CBF). Blocking AT1R is not sufficient during the acute phase of stroke. AT1R-induced vasoconstriction follows Gq protein activation, while its internalization is due to β-arrestin activation. The latter could have protective effects during stroke. Thus, we aimed to first investigate the blood pressure (BP) dependent and independent effects of a AT1R biased agonist (receptor-specific ligands able to selectively activate a single signaling pathway) on the CBF in mice. 10- to 12-week-old C57BL6/J male mice were operated to allow the placement of vessel catheters (n=5). Anesthetics (ketamine/medetomidine) was perfused via the jugular vein, BP was monitored via a catheter in the femoral artery and drugs and saline solutions were injected via the left carotid artery to study their impact on CBF. CBF was measured transcranially using Laser Speckle Contrast Imaging (0.46 frames/s, 0.010mm resolution). The impact of AngII on CBF was studied at a pressive and non-pressive dose before and after infusion of the AT1R biased agonist TRV120027 (50nmol/kg). Before TRV120027 infusion, the pressive dose of AngII (2 nmol/kg) increased SBP (+33±14 mmHg, p=0.006) and CBF (+17±13 % p=0.04) while the non-pressive dose of AngII (0.05 pmol/kg) had no effect on both parameters. TRV120027 decreased SBP (-21±16 mmHg, p=0.04) and CBF (-5.8±4.3 %, p=0.04). To pursue our investigations on the impact of TRV120027 on AngII mediated CBF changes, a lower dose of TRV120027 will be studied in an upcoming study. Our initial findings indicate that the chosen pressive and non-pressive doses of AngII are appropriate and TRV120027 by itself reduces BP and thereby CBF. This also demonstrates the ability of this AT1R biased agonist to reduce systemic vascular resistance, leading to a decrease in BP.

Domains

Pharmacology
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Dates and versions

hal-04586988 , version 1 (24-05-2024)

Identifiers

  • HAL Id : hal-04586988 , version 1

Cite

Mélissa Colin, Peter Leenders, Caroline Perrin, Matthijs W Blankesteijn, François Dupuis, et al.. Physiological effects of a biased Angiotensin II type 1 receptor agoniston blood pressure and cerebral blood flow. Dutch Neuroscience Meeting, Jun 2023, Tiel, Netherlands. ⟨hal-04586988⟩
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