Abstracts e423

MPS 18-01 MODE OF ACTION OF RB150, AN ROS levels were increased 1.7-fold in smPparγ–/– and 2.5-fold in eET-1/sm E
AMINOPEPTIDASE A INHIBITOR PRODRUG AS A Pparγ–/–. Monocyte/macrophage infiltration in PVAT was 2-fold higher in eET- S
CENTRALLY-ACTING ANTIHYPERTENSIVE AGENT 1 and smPparγ–/–, which was further increased 2-fold in eET-1/smPparγ–/–. The D
IN DOCA-SALT HYPERTENSIVE RATS percentage of CD11b+ cells was increased 2.3-fold in smPparγ–/– and further in-
creased 1.5-fold in eET-1/smPparγ–/–. The percentage of Ly-6Chi monocytes was
Réda Hmazzou, Adrien Flahault, Yannick Marc, Catherine Llorens-Cortes. increased ~1.8-fold in eET-1 and sm Pparγ–/– but not eET-1/smPparγ–/–. The per-
Department of Physiology, Collège de France, France centage of T regulatory cells was increased 1.5-fold in smPparγ–/– and decreased
Objective: In the brain, angiotensin III (AngIII) generated from angiotensin by 26% in eET-1, which was further decreased by 38% in eET-1/smPparγ–/–. P
II (AngII) by aminopeptidase A (APA) exerts a tonic stimulatory action on the O
Conclusions: These results suggest that increased ET-1 paradoxically preserves
control of blood pressure (BP) in hypertensive rats. Inhibition of brain APA by endothelial function in mice with inactivated VSMC Pparγ despite enhanced
RB150, an orally active prodrug of the specific and selective APA inhibitor, blocks oxidative stress. Flow cytometry data indicate that infiltrating monocyte/macro-
brain AngIII formation and normalizes BP in hypertensive rats. Since following phages in these mice might be anti-inflammatory. E
blockade of brain AngIII formation by RB150, no AngII accumulation was ob- R
served, we aimed to delineate if this treatment induces the activation of another
metabolic pathway of brain AngII, in particular angiotensin converting enzyme MPS 18-03 VITAMIN C PREVENTS DECREASE OF BLEEDING
type 2 (ACE2) which converts AngII into angiotensin 1–7 (Ang1–7). TIME; AN EXPERIMENTAL STUDY USING MICE
Design and Method: For this purpose, RB150 and MLN4760, an ACE2 inhibi-
tor, were administered by intracerebroventricular (ICV) route after insertion of an Alles Firmansyah1, Zelly Dia Rofinda2, Erkadius Erkadius3. 1Department of
intracerebral cannula to alert DOCA-salt rats, a model of salt-dependent hyperten- Clinical Student, Faculty of Medicine Andalas University, Indonesia, 2Depart-
sion. Mean arterial blood pressure (MABP) was recorded via an arterial femoral ment of Clinical Pathology, Faculty of Medicine Andalas University, Indonesia,
3Department of Physiology, Faculty of Medicine Andalas University, Indonesia
catheter. Maximal MABP decrease and area under the curve (AUC) of the varia-
tions in MABP were calculated. Objective: Cigarette smoke is one of the leading causes of preventable deaths in
Results: ICV administration of RB150 (100 μg) significantly decreased MABP the world. World Health Organization (WHO) 2015 reported 6,000,000 people are
compared to vehicle (–23 ± 3 mmHg vs –6 ± 2 mmHg; AUC: 17.6 ± 2 vs estimated to die annually from cigarette smoke, with over 600,000 deaths due to
2.1 ± 3). Administration of MLN4760 (10 μg) didn’t induce any significant exposure second-hand smoke. Cigarette smoke known to enhance Reactive Oxy-
change of MABP compared to vehicle (–10 ± 3 mmHg; AUC: 1.4 ± 2). Co- gen Species (ROS). ROS could damage vascular and alter platelet reactivity that
administration of MLN4760 (10 μg) with RB150 (100 μg) partially inhibits makes decrease of bleeding time as an indicator of thrombosis risk factor effect.
RB150-induced BP decrease. Vitamin C as an essential antioxidant was proven to reduce oxidative stress due to
ROS. We aimed to prove that vitamin C could prevent decreases bleeding time of
Conclusions: In conclusion, ICV administration of the ACE2 inhibitor alone has mice induced cigarette smoke.
no effect on BP indicating that in DOCA-salt rats, brain Ang1–7 does not exert a
tonic stimulatory effect on the control of BP. However, when conversion of brain Design and Method: An experimental study with randomized pre test-post test
AngII into AngIII is blocked by RB150, there is an activation of the conversion control group design was conducted on 21 mice divided equally into three groups.
by ACE2 of brain AngII into Ang1–7, which by acting on the Mas receptor, may Group I as control; group II was given cigarette smoke in 10 minutes per day, and
participate to the RB150-induced BP decrease in hypertensive rats. group III was given vitamin C 0,4 mg/gW/day + cigarette smoke in 10 minutes
per day, respectively, for two weeks. The bleeding time was determined by a tail
bleeding method on day 0 and day 15. T-paired and LSD post-hoc test were used
to analyze the data. A P-value less than 0.05 considered significant.
VASCULAR SMOOTH MUSCLE CELL-SPECIFIC Results: The result showed that group I had not a significant difference in mean
DELETION OF PPAR-GAMMA of bleeding time from 60.16 ± 3.27 to 57.61 ± 4.88 seconds. Group II had a
significant difference in mean of bleeding time from 59.34 ± 6.93 to 38.85 ±
Sofiane Ouerd1, Noureddine Idris-Khodja1, Michelle Trindade2, Jordan Gornitsky1, 3.43 seconds. Group III had a significant difference in mean of bleeding time from
Asia Rehman1, Stefan Offermanns3, Frank Gonzalez4, Tlili Barhoumi1, Pierre Para- 59.36 ± 3.07 to 51.85 ± 3.45 seconds. Group II and group III had a significant
dis1, Ernesto Schiffrin1. 1Hypertension and Vascular Research Unit, Lady Davis difference in post-test mean of bleeding time (p = 0.000).
Institute for Medical Research, Canada, 2Department of Clinical Medicine, State
University of Rio de Janeiro, Brazil, 3Department of Pharmacology, Max-Planck- Conclusions: This research proves that vitamin C could prevent decreases of bleed-
Institute for Heart and Lung Research, Germany, 4Department of Metabolism, Na- ing time. Further study is needed find out the effective dose and its potency in human.
tional Cancer Institute, U.S.A.
Objective: Peroxisome proliferator-activated receptor γ (PPARγ) agonists reduce MPS 18-04 FASUDIL PREVENTS CORONARY
blood pressure (BP) and vascular injury in hypertensive rodents. Pparγ inactiva- MICROVASCULAR ENDOTHELIAL DYSFUNCTION
tion in vascular smooth muscle cells (VSMC) using a tamoxifen inducible Cre- AND CARDIAC CONTRACTILE DYSFUNCTION IN A
Lox system enhanced angiotensin II-induced vascular damage. Transgenic mice RAT MODEL OF HYPERTENSIVE DIABETES MORE
overexpressing endothelin (ET)-1 in the endothelium (eET-1) exhibit endothelial THAN LOSARTAN
dysfunction, increased oxidative stress and inflammation. We hypothesized that
James Pearson1, Hirotsugu Tsuchimochi1, Tadakatsu Inagaki2, Cheng-Kun Du1,
inactivation of the Ppar gene in VSMC (smPparγ–/–) will exaggerate ET-1-in-
Dong-Yun Zhang1, Daryl Schwenke5, Amanda Edgley4, Keiji Umetani3, Naoto
duced vascular damage.
Yagi3, Mikiyasu Shirai1. 1Department of Cardiac Physiology, National Cerebral
Design and Method: Eleven week-old male control, eET-1, smPparγ–/– and eET- and Cardiovascular Center, Japan, 2Department of Vascular Physiology, National
1/smPparγ–/– mice were treated with tamoxifen (1 mg/kg/day, s.c.) for 5 days and Cerebral and Cardiovascular Center, Japan, 3Biomedical Imaging Center, Japan
sacrificed 4 weeks later. BP was measured by telemetry. Endothelial function and Synchrotron Radiation Research Institute, SPring-8, Japan, 4St Vincent Hospital,
vascular remodeling using pressurized myography, reactive oxygen species (ROS) University of Melbourne, Australia, 5Department of Physiology, University of
production by dihydroethidium staining, monocyte/macrophage infiltration by Otago, New Zealand
immunofluorescence and mRNA expression by reverse transcription-quantita- Objective: Diabetes, hypertension and obesity are risk factors for the develop-
tive PCR were assessed in mesenteric arteries (MA) or perivascular fat (PVAT). ment of heart failure. Rho kinase (ROCK) appears to drive the coronary and con-
Spleen T cell and monocyte profiles were assessed by flow cytometry. tractile dysfunction in early diabetes and in hypertension. We hypothesised that
Results: Systolic BP was 20 mmHg higher in eET-1 and unaffected by Pparγ ROCK activation plays a critical role in diabetic heart failure.
inactivation. MA vasorelaxation to acetylcholine was impaired 37% only in smP- Design and Method: Using synchrotron radiation microangiography and in vivo
parγ–/–. Likewise, ET-1-induced contractions were enhanced only in smPparγ–/–. small-angle X-ray scattering (SAXS) approaches, we investigated the effect of

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.