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Caffeic Acid Ameliorates Angiotensin Ii Induced.729
Caffeic Acid Ameliorates Angiotensin Ii Induced.729
Caffeic Acid Ameliorates Angiotensin Ii Induced.729
E-POSTERS
E P19 EXPERIMENTAL HYPERTENSION AND PHARMACOLOGY Moreover, compared with the levels in the WKY+HHcy group, mean SOD lev-
els in the SHR+HHcy group were lower, while mean MDA and UACR levels
P were higher. Higher mRNA and protein expression levels of NOX2 and NOX4,
O along with lower mRNA and protein expression levels of nephrin, were observed
S in the kidneys of WKY+HHcy and SHR+HHcy rats, relative to SHR and WKY
T ALTERED EXPRESSION OF LUNG EPITHELIAL ION AND FLUID controls, respectively. Furthermore, the mRNA and protein levels of NOX2 and
E TRANSPORTERS DURING PROGRESSION OF PULMONARY NOX4 were higher and the mRNA and protein levels of nephrin were lower in the
R HYPERTENSION IN THE MONOCROTALINE MODEL SHR+HHcy group than in the WKY+HHcy group. In addition, compared with
S Katarina Zirova, Zuzana Kmecova, Jana Veteskova, Martina Podzubanova, Jan
WKY+HHcy group, the UACR level of SHR group was higher.
Klimas, Peter Krenek. Comenius University in Bratislava, Faculty of Pharmacy Conclusions: HHcy appears to synergistically increase hypertensive renal dam-
- Department of Pharmacology and Toxicology, Bratislava, SLOVAK REPUBLIC age by enhancing oxidative stress. However, hypertension remains a major risk
factor for renal impairment compared to HHcy.
Objective: Recent studies have evaluated a significant incidence of pleural ef-
fusions in patients with idiopathic and heritable pulmonary arterial hypertension
(PAH) co-diagnosed with isolated right-sided heart failure (RHF). Coincidence of RESVERATROL PROTECT AGAINST HOMOCYSTEINE-INDUCED
pleural effusions and RHF in these patients significantly increased mortality rate RENAL DAMAGE THROUGH ANTIOXIDANT ACTION IN
during follow-up. However, mechanism of pleural effusions formation has not SPONTANEOUS HYPERTENSIVE RATS
been fully explained. Therefore, we examined expression of lung epithelial ion
Rui Xu1, Qingchen Hui1, Xuan Zhao2. 1Hospital of Shandong First Medical Uni-
and fluid transporters responsible for alveolar fluid clearance (AFC), which may
versity, Jinan, CHINA, 2People’s hospital of Dongying, Dongying, CHINA
contribute to lung fluid accumulation under pathological conditions and poten-
tially formation of pleural effusions. Objective: The aim of this study was to investigate the effect of resveratrol in
renal damage and the underlying mechanism induced by Hhcy in SHRs.
Design and method: 12-weeks old male Wistar rats were subcutaneously in-
jected with monocrotaline (60 mg/kg, MCT) or vehicle (CON). The relative ex- Design and method: Twenty-four SHRs were divided into control group, Hhcy
pression of AFC transporters: Na+/K+-ATPase alpha1, alpha2, beta1, beta3 sub- group, Hhcy + resveratrol (Hhcy+Res) group. Hhcy groups were given intraperi-
units, epithelial sodium channel (ENaC) alpha, beta, gama subunits, cystic fibrosis toneal injection of homocysteine. In addition, the Hhcy + Res group was given
transmembrane conductance regulator (CFTR) were determined by RT-qPCR 1, 2, resveratrol by gavage. The Systolic blood pressure (SBP), diastolic blood pres-
4 weeks after MCT application and also in end-stage disease (animals sacrificed sure (DBP), plasma Hcy, serum malondialdehyde (MDA), superoxide dismutase
after acute health deterioration, ~ 4 weeks after MCT application) where pleural (SOD) and the urinary microalbumin (UACR) were measured. To quantify RNA
effusions were observed. and protein expression levels, the mRNA and the protein expression of nephrin
and NADPH oxidase subunits NOX2 and NOX4 in the kidney were examined by
Results: Increase in lung weight was observed from second week after MCT
quantitative Real-time PCR and western blot. Renal histological or pathological
application and was more profound in end-stage disease (by 26 % compared to
changes were observed under light and electron microscope.
fourth week, p<0.05). A downregulation of all three pore-forming subunits of
ENaC was observed in end-stage disease, accompanied by downregulation of Results: There was no difference in blood pressure before and after Hcy or Res
small beta3 subunit of Na+/K+-ATPase. Expression of catalytic alpha2 subunit intervention among groups. The homocysteine levels in Hhcy and Res group were
of Na+/K+-ATPase gradually decreased with disease progression from first week significantly higher than that in control group, which showed that the model was
after MCT (-80% in end-stage vs. CON, p<0.05). On the other hand, we observed successfully built by intraperitoneal injection. The serum SOD level was signifi-
upregulation of CFTR (by 80%) and beta1 subunit of Na+/K+ATPase (by 79% vs. cantly decreased in Hhcy group, while it was increased in Res group. On the
CON, p<0.05) mainly in end-stage disease. contrary, the serum MDA and UACR levels of model group were significantly
increased. after the intervention of resveratrol, the MDA and UACR levels were
Conclusions: Downregulation of lung epithelial ion and fluid transporters con-
reduced. Furthermore, the expression levels of mRNA and the protein of NOX2
tributing to AFC is predominantly limited to higher stages of PH with a marked
and NOX4 were elevated while those of the nephrin were reduced in Hhcy group.
downregulation in end-stage. These expression alterations may contribute to over-
Resveratrol significantly reduced the expressions of NOX2 and NOX4, and in-
all lung weight increase observed in end-stage disease. However, observed early
creased the expression of nephrin in renal tissue of SHRs with Hhcy.
alpha2 subunit of Na+/K+-ATPase downregulation could participate on the patho-
genesis of PH while upregulation of beta1 subunit and CFTR in end-stage disease Conclusions: These results suggested that resveratrol may improve renal damage
could represent a compensatory mechanism. in hypertensive rats with Hhcy by exerting oxidative stress beyond blood pressure.
ship between HHcy and hypertension in renal injury remains unclear. Here, tary Medical University, Chongqing, CHINA
we sought to evaluate the relationship between HHcy and hypertension in the
Objective: Many studies have focused on reporting the beneficial effect of con-
context of renal injury and to elucidate the mechanism of action underlying
sumption coffee or caffeine on cardiovascular disease. However, caffeic acid, a
this relationship.
component of coffee, which has a completely different structure from caffeine,
Design and method: Wistar Kyoto (WKY) and spontaneously hypertensive was rarely studied in cardiovascular metabolic diseases. In this study, we investi-
(SHR) rats were randomized into WKY, WKY+HHcy, SHR, and SHR+HHcy gated the effect of caffeic acid on vascular function and blood pressure of mice.
groups. Blood pressure, plasma homocysteine, creatinine, serum malondialde-
Design and method: Tension of endothelium-free mesenteric arteries from
hyde (MDA), serum superoxide dismutase (SOD), and urinary albumin creatinine
8-week-old male wild-type (WT) mice was measured using wire myograph.
ratio (UACR) were measured. mRNA and protein expression levels of NOX2,
Cytoplasmic Ca2+ and sarcoplasmic reticulum (SR) Ca2+ were measured from
NOX4, and nephrin in the kidneys were also examined.
primary vascular smooth muscle cells (VSMCs) using fura-2AM and mag-fura-
Results: The WKY+HHcy group exhibited lower serum SOD levels, relative to 2AM, respectively. Molecular docking was performed by AutoDock to determine
the WKY group, along with higher levels of both serum MDA and UACR. Simi- the binding force and sites of caffeic acid with sarco-/endoplasmic reticulum
lar effects were observed in the SHR+HHcy group, relative to the SHR group. Ca-ATPase (SERCA, a channel transporting Ca2+ from the cytosol into the SR
lumen. PDB: 2YFY). 8-week-old male SERCA2a knockout mice and WT litter- Objective: Four different antihypertensive agent classes are equivalently recom-
mates were surgically implanted with mini-osmotic pumps filled with angiotensin mended in the guidelines for first-line treatment of arterial hypertension (AHT).
II (Ang II) solutions. Then these mice were fed with normal diet or 0.05% caffeic However, it is unclear, if one of these agents is more potent than the others to reach
acids in drinking water for 8 weeks. The tail-cuff blood pressure (BP) and 24-hour blood pressure (BP) control. We sought to compare response rates and BP control
ambulatory BP were measured. in these four classes.
Results: First, we found that caffeic acid relaxed mesenteric artery pre-contracted Design and method: Patients with newly diagnosed grade 1 or 2 AHT on
with norepinephrine (NE) with half-effective dose of 26.7uM. Furthermore, pre- 24h-BP measurements (ABPM) were randomized in a 1:1:1:1 fashion to either
treatment with 50uM caffeic acid for 5 min completely smoothed NE-induced perindopril (ACE), olmesartan (ARB), amlodipin (CCB) or hydrochlorothiazide
vasoconstriction. Specifically, we found that caffeic acid reduced intracellular (HCT). ABPM were checked at baseline (BL), after 4 weeks of half dose (TP1)
Ca2+ in a concentration-dependent manner as well as resisted the increase of and after 4 weeks of full dose (TP2), if BP control was not reached after TP1.
intracellular Ca2+ induced by thapsigargin, a SERCA inhibitor, whereas caffeic Patients were classified as controlled if mean BP was < 130/80 mmHg, awake BP
acid increased SR Ca2+ uptake. Molecular docking revealed caffeic acid binds < 135/85 mmHg and night BP < 120/70 mmHg.
to SERCA to form strong hydrogen bonds at ASN-359, TYR-389, ARG-604 and
Results: 80 patients were randomized: 20 (25.0%) to ACE, 20 (25.0%) to ARB, 21
ASP-738. Eventually, we found that compared with the normal diet group, the
(26.3%) to CCB, and 19 (23.8%) to HCT. Mean age was 48 (±14) years, mean BMI
intervention of caffeic acid significantly attenuated AngII-induced increases of
26.5 (±3.7) kg/m2. Mean 24 h systolic BP (sBP) was 141.8 (± 9.1) mmHg, diastolic
tail BP and ambulatory BP in mice, but the hypotensive effect of caffeic acid
BP (dBP) 87.8 (± 7.6) mmHg (Table). Mean decrease from BL to TP1 was -5.8 (±
disappeared in SERCA2a knockout mice.
10.9) and -2.7 (± 5.6) mmHg, from BL to TP2 -11.6 (± 11.2) and -5.6 (± 6.7) mmHg,
Conclusions: These results suggest that caffeic acid has a beneficial effect on from TP1 to TP2 -5.8 (± 12.0) and -2.8 (± 5.4) mmHg, for mean 24 h sBP and dBP,
vascular function and blood pressure by activating SERCA2a on VSMCs. Con- respectively. After TP1, 21 patients (26.3%) had a controlled BP overall (Figure). Af-
sumption coffee or caffeic acid may be an effective lifestyle to prevent and treat ter TP2, the number of controlled patients increased to 24 patients (30.0%, p=0.250,
hypertension. Figure). Control rates were significantly lower for HCT in comparison to the other
agents for diastolic values after TP1 (p=0.013) and after TP1 and TP2 (p=0.003).
MICRORNA PROFILE IN HUMAN VASCULAR SMOOTH MUSCLE
CELLS FROM HYPERTENSIVE SUBJECTS: FOCUS ON OXIDATIVE
AND ENDOPLASMIC RETICULUM STRESS