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HTA et microcirculation (E.Vicaut)

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Information about HTA et microcirculation (E.Vicaut)
Health & Medicine
hta

Published on June 17, 2008

Author: jfg

Source: slideshare.net

Description

www.fedret.fr : HTA et oeil (12 juin 2008)
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HYPERTENSION ET MICROCIRCULATION Eric VICAUT Laboratoire d’Etude de la Microcirculation Université Paris 7

Pourquoi s’interesser à la microcirculation ?

Le site majeur de la régulation du niveau de pression artérielle 10 30 50 70 90 110 130 150 mmHg Vessel Diameter (µm) 5 10 100 1000 e

LES CHANGEMENTS FONCTIONNELS ASSOCIES A L’HTA

Functional changes in microcirculation during HT Decrease in NO-dependent dilation Increase in vasoreactivity to constrictive mediators

Decrease in NO-dependent dilation

Increase in vasoreactivity to constrictive mediators

Reduction in NO-dependent dilation in skin microcirculation in HT patients De jongh Circulation 2004

NO-production in retinal arterioles of HT patients Delles Stroke 2004

Local Microvascular RAS in HT Vicaut et al. Hypertension

Pressure-Induced Generation of Superoxide in Femoral Arteries From Ungvari et al. Circulation 2003

Hemoxygenase and HT A:Sham B:DOCA C:WKY D:SHR With chromium mesoporphyrin

Xanthine Oxidase enzymes in Dexamethasone –induced HT Wallwork CJ et al. Microvasc Res 2003

Schema of the possible interactions among NO, ROS, and prostanoids + - ROS COX Pathway TBXA 2 PGI 2 NO + - COX Pathway NO TBXA2 PGI 2 ROS Laemmel et al. Am J Physiol 2004

LES CHANGEMENTS STRUCTURAUX ASSOCIES A L’HTA

Remodelage artèriel et artériolaire Intima Média Adventice Normotendu Hypertendu

Arterioles and Capillary Rarefaction Hypertensive Normotensive

Capillary Rarefaction in Patients Antonios T. Hypertension 1999

Targets for interactions between ROS and signaling system in vascularsmooth muscle and endothelial cells From Wolin MS et al. J Vasc Res 2002

Microvessels Rarefaction in NOS- HT Kubis et al. J Hypertension 2002

Leucocytes Pseudopods in HT Fukuda et al. Circ Res 2004

CONSEQUENCES TISSULAIRES

La raréfaction capillaire altère la perfusion tissulaire O 2 Levy BI, Ambrosio G, Pries AR, Struijker-Boudier HA. Microcirculation in hypertension:a new target for treatment? Circulation 2001a;104:735-740. Normotendu Hypertendu Raréfaction Altération de la perfusion Perfusion normale Artériole Veinule Capillaire

Tissue PO2 recovery Post-exercise Smith LM et al. Am J Phys Heart and Circ 2004

TISSUE PO2 IN BORDERLINE HYPERTYENSION Jung et al. Clin Inv 1993

UNE ATTEINTE TRES PRECOCE

Microvascular disorders as a predictor of HT Prospective Cohort during 10 Years Wong BMJ 2004

Capillary Rarefaction In Young Adults with Predisposition to HT Noon J.Clin Invest 1997

Conclusions

Changements fonctionnels associés à l’ HTA Augmentation de réactivité aux substances vasoconstrictives Effets directs. Antagonistes calciques IEC, Antagonistes des récepteurs Ang II Bloqueurs du système adrénergiques

Augmentation de réactivité aux substances vasoconstrictives

Effets directs.

Antagonistes calciques

IEC, Antagonistes des récepteurs Ang II

Bloqueurs du système adrénergiques

Local Microvascular RAS in HT Vicaut et al. Hypertension

Reduction in NO-dependent dilation in skin microcirculation in HT patients De jongh Circulation 2004

Changements fonctionnels associés à l’ HTA Diminution de synthèse des substances dilatatrices (NO, PGI2) Effets directs. IEC Effets indirects IEC, Antagonistes des récepteurs Ang II

Diminution de synthèse des substances dilatatrices (NO, PGI2)

Effets directs.

IEC

Effets indirects

IEC, Antagonistes des récepteurs Ang II

By courtesy of P.Vanhoutte Effets directs et indirects des IEC 1/ Modulation directe de la production de NO par l’augmentation de Bradykinine

L’HTA augmente le stress-oxidatif From Ungvari et al. Circulation 2003

Les récepteurs AT1 modulent la surexpression de la NAD(P)H Oxidase

Effets directs et indirects des IEC et des Antagonistes de l’Ang II 2/ Modulation indirecte de la biodisponibilité du NO par l’intermédiaire de l’Ang II ANG II  AT1  Augmentation du stress oxydatif ROS NO 3/ Effet anti-oxydant de certains diurétiques : indapamide

Interactions NO, ROS, et prostanoides + - ROS COX Pathway TBXA 2 PGI 2 NO + - COX Pathway NO TBXA2 PGI 2 ROS Laemmel and Vicaut. Am J Physiol 2004

LES CHANGEMENTS STRUCTURAUX ASSOCIES A L’HTA

Effets des IEC et des Antagonistes de l’Ang II sur la densité capillaire

Levy BI, Duriez M, Samuel JL. Coronary microvasculature alteration in hypertensive rats. Effect of treatment with a diuretic and an ACE inhibitor. Am J Hypertens . 2001;14:7-13. perindo+ indapamide Effets d’une bitherapie IEC + Diurétique

L’absence de NO induit une raréfaction microvasculaire Kubis et al. J Hypertension 2002

Effet anti-angiogénique de l’Ang II ANG II  AT2  Effet Anti-angiogénique Empêche l’effet pro-angiogénique de l’ischémie Sylvestre et al. Circ Res 2002

ANG II  AT2  Effet Anti-angiogénique

Empêche l’effet pro-angiogénique de l’ischémie

Conclusions

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