bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 280: Protein Tyrosine Phosphatase Oxidation and Redox Proteomics in Hypertension
Authors: Tsiropoulou Sofia , Montezano Augusto C , Scott Alan , Burchmore Richard J , Touyz Rhian M
Published: March 2022

Aberrant signalling and vascular dysfunction in hypertension (HTN) have been associated with reactive oxygen species (ROS)-induced oxidation of redox-sensitive molecules. Protein tyrosine phosphatases (PTP) are susceptible to oxidation of thiols (-SH) at their active site, which leads to PTP inactivation. We hypothesize that oxidative stress is associated with reversible PTP oxidation and consequent reduced PTP activation in HTN. VSMCs from normotensive and hypertensive rats (WKY and SHRSP) were stimulated with AngII (10-7 M) and ET-1 (10-7 M). Protein oxidation was assessed by the oxyblot assay. PTP oxidation, TC-PTP and PTP1B expression levels were assessed by immunoblotting. Differential gel electrophoresis (DiGE) of CyDye-labelled cell lysates was employed for screening of oxidized proteome. Global-protein and PTP-specific oxidation was increased in VSMCs from SHRSP versus WKY (fold change (FC)=1.29 and FC=1.53, p<0.05, respectively). AngII stimulation did not affect global oxidation in either WKY or SHRSP, but increased PTP-oxidation in WKY (FC=1.47 at 5min, p<0.05) to levels similar to SHRSP. Stimulation with ET-1 increased total oxidation only in WKY (FC=1.52 at 15min, p<0.05) but not SHRSP, and had no effects on PTPs oxidation. Moreover, stimulation with AngII and ET-1 reduced protein expression of TC-PTP (FCAngII=0.8 at 2h for WKY; FCAngII=0.9 at 1h for SHRSP; FCET1=0.8 at 2h for WKY and 1h for SHRSP) and PTPB1 (FCAngII=0.87 at 1h for WKY and SHRSP; FCET1=0.9 at 2h for WKY and SHRSP), (p<0.05). DiGE proteomic data, filtered for FC>2, detected 1777 spots of which 1388 (78.1%) were equally oxidized across SHRSP and WKY, and 264 (14.9%) exhibited increased oxidation levels in SHRSP. Our findings demonstrate that oxidation of PTPs is increased in VSMCs from hypertensive rats and that vasoactive agents differentially regulate PTP oxidation and their expression levels in HTN. Furthermore, the oxidized state of 21.9% of the global proteome is altered in disease. Ongoing studies, in both rats and humans, are focusing on the characterization of a PTP-oxidation signature in HTN. Identification of specific PTPs which are deregulated in HTN could elucidate aberrant redox signalling in vascular dysfunction and highlight novel therapeutic targets.
Abstract 287: Evidence For Increased Autophagy In Fetoplacental Units Of Bph/5, A Mouse Model Of Pre-eclampsia (PE)
Authors: Valbuena-Diez Ana Cristina , Sones Jenny L , Butler Scott D , Patel Unisha , Davisson Robin L
Published: March 2022

Autophagy, a mechanism of cell survival during times of stress, plays an important role in normal placentation, protecting the fetus during fluctuations in conditions such as nutrient availability. In cases of placental insufficiency, often present in PE, autophagy may be defective. We have shown that BPH/5 mice, in addition to spontaneously developing a PE-like syndrome including late-gestational hypertension and proteinuria, exhibit abnormal placentation and poor feto-placental outcomes. Here we tested the hypothesis that there is increased autophagy in fetoplacental units (FPUs) of pregnant BPH/5 females. RNA was extracted from FPUs (e10.5) of BPH/5 and C57 control mice and analyzed for biomarkers of autophagy. BPH/5 showed a significant increase in both Beclin-1 and LC3-β compared to C57 (1.5-fold for each, n=7; p<0.05). Increased autophagy in e10.5 BPH/5 FPUs was corroborated at the protein level using ELISA to measure Beclin-1 (0.6±0.1 control vs. 2±0.17 ng/mL BPH/5; n=7; p<0.05). We also analyzed protein levels of p62, an autophagy biomarker which is degraded during autophagy. Consistent with these other findings, the levels of p62 were lower in BPH/5 mice (29.7±2.5 controls vs. 7.2±1.3 ng/mL BPH/5, p<0.05). Given that autophagy in trophoblasts plays a key role in the invasion of these cells and thus remodeling of uterine arteries, we examined the invasion capacity of e10.5 trophoblasts isolated from C57 and BPH/5 mice. Trophoblasts from BPH/5 mice were much less invasive when compared to C57 (2-fold decrease, n=7; p<0.05). Inhibition of autophagy with chloroquine diphosphate (50 μM) significantly improved invasion capacity of these cells (1.6-fold increase; n=7; p<0.05). Collectively, these data demonstrate that autophagy is defective in FPUs from BPH/5 mice, and suggest that this may play a causal role in PE in this model.
Abstract 292: Vitamin D Supplementation Reduces CD4+ T Cells, Blood Pressure and Autoantibodies to the AT1 Receptor (AT1-AA) in a Rat Model of Preeclampsia
Authors: Faulkner Jessica L , Darby Marie M , Cornelius Denise C , Moseley Janae , Herse Florian , Dechend Ralf , LaMarca Babbette
Published: March 2022

Preeclampsia (PE) is characterized by the development of hypertension, endothelial dysfunction and chronic immune activation after 20 weeks of gestation. PE women exhibit elevated CD4
+
T cells, proinflammatory cytokines and agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA). Vitamin D deficiency is associated with increased prevalence of hypertension and chronic inflammatory diseases both in the presence and absence of pregnancy. We utilize the Reduced Uterine Perfusion Pressure (RUPP) model of PE in the pregnant rat which exhibits hypertension, endothelial dysfunction as well as increased CD4
+
T cells, inflammatory cytokines and AT1-AA. Therefore, we tested the hypothesis that administration of exogenous Vitamin D2 (VD2) and Vitamin D3 (VD3) would ameliorate hypertension and or chronic inflammation associated with placental ischemia in the RUPP rat. For these studies, the RUPP procedure was performed on gestation day 14 (GD14) and normal pregnant (NP) and RUPP rats were treated daily with 50uM VD2 or VD3 via oral gavage on GD14-18. Carotid catheters were inserted on GD18 and blood pressure (MAP), blood and tissues were collected on GD19. Flow cytometry was used to evaluate CD4
+
T cells in control RUPP rats and RUPP rats treated with Vitamin D. On GD19, MAP was increased in RUPP rats to 123 ± 3.5 compared to 108.8 ± 4.3 mmHg in NP rats (n=5-6, p<0.05). Supplementation with either VD2 or VD3 lowered MAP to 113 ± 6.9 or 115.4 ± 2.3 mmHg, respectively (n=4-5). CD4
+
T cells in RUPP compared to NP rats increased from 2.80 ± 0.95 to 8.49 ± 1.52 percent (n=8-11, p<0.05). Circulating CD4
+
T cells fell to 1.22 ± 0.41 percent with VD2 and to 4.59 ± 3.67 percent with VD3 (n=2-3). AT1-AA levels, measured via chronotropic response in cardiomyocytes, were 19.50 ± 0.44 beats/min in RUPP rats and decreased to 15.35 ± 0.69 with VD3, and further to 8.33 ± 0.51 with VD2 supplementation (n=5, p<0.05). Taken together, these data indicate that pharmaceutical Vitamin D supplementation reduced blood pressure and markers of chronic inflammation in a rat model of PE, thereby suggesting a role for Vitamin D supplementation to improve hypertension and chronic inflammation in response to diseases associated with placental ischemia, such as PE.
Abstract 303: Decreased Adrenomedullin and Interaction with NHE3 in Human
GRK4
γ

142v

Transgenic Mice
Authors: Zhou Donghai , Jones John , Asico Laureano , Jose Pedro A , Wang Xiaoyan
Published: March 2022

The expression of the human G protein-coupled receptor kinase 4γ (GRK4γ) 142V variant (hGRK4γ

142V

)

in mice causes hypertension that is related to dysfunction of renal dopaminergic and renin-angiotensin systems. To determine if there are other dysfunctional systems in hGRK4γ

142V

mice, we quantified the expression of adrenomedullin (ADM), a natriuretic hormone, and components of its receptor, RAMP2 (receptor activity-modified protein2), CLCR (calcitonin-like calcitonin receptor), and ADMRL2 (ADM receptor L2) in the kidneys of
hGRK4
γ

142V

and
hGRK4
γ

WT

transgenic mice and non-transgenic (NT) littermates
.
Systolic blood pressure (measured under anesthesia) was elevated in
hGRK4
γ

142V

(129.3±10.4, mm Hg) but not in
GRK4
γ

WT

mice (101.7±6.3), relative to NT littermates (99.8±1.8) (n=4/group). The sodium excretion and blood pressure plot in
GRK4
γ

142V

mice was shifted to the right of
GRK4
γ

WT

mice. Protein expressions of ADM (37±4% of NT by immunoblotting and immunofluorescence) and RAMP2 (36±16%) were decreased in
hGRK4
γ

142V

mice but unchanged in
GRK4
γ

WT

mice, relative to NT littermates. The protein expressions of CLCR and ADMRL2 were not altered in
hGRK4
γ

142V

and
GRK4
γ

WT

. In the kidney ADM colocalized with NHE3 but not with NKCC2 and NCC. NHE3 protein expression in renal homogenates and brush border membranes was not altered in
GRK4
γ

142V

mice. However, the amount of NHE3 that coimmunoprecipitated with ADM was decreased in
GRK4
γ

142V

(77±3% of NT) mice; a similar decrease was also found in the reverse-coimmunoprecipitation of NHE3 with ADM.
In vitro
, human ADM inhibited apical sodium transport in polarized human renal proximal tubule cells (1 hr, n=5-6) at concentrations of 10 nM (84±4 % of vehicle) and 100 nM (81±3%), similar to that achieved with the NHE3 inhibitor EIPA (81±6%, 100 nM), suggesting that NHE3 activity was inhibited by ADM. Our data suggest that GRK4γ

142V

decreases ADM/RAMP2 expression in the kidney; the natriuretic effect of ADM may depend mainly on the inhibition of the activities of sodium transporters along the nephron (e.g., NHE3). The decreased ADM/NHE3 interaction and dysfunctional natriuretic and antinatriuretic factors may contribute to the impaired sodium excretion and increased blood pressure in
GRK4
γ

142V

transgenic mice.
Abstract 315: Endothelial And Autonomic Dysfunctions Induced By High Fructose Intake Are Modulated By The Angiotensin Converting Enzyme (ACE) Gene Dosage
Authors: Moraes-Silva Ivana C , Souza Leandro E , Irigoyen Maria-Claudia , Casarini Dulce E
Published: March 2022

ACE gene polymorphism may be associated with different responses to physiological and pathological stimuli. Therefore, we tested whether low, normal or high levels of ACE gene dosage influence on the effects of chronic and excessive fructose intake (F).

Male mice (22±1g) harboring 1, 2 or 3 copies of the ACE gene received F (100g/l) or tap water for 8 weeks. After this period, glucose tolerance (0-120 min after glucose load=1.5 g/Kg ip) and lipids were measured; blood pressure (BP) signals were recorded (Windaq, 4kHz), and BP variability was analyzed in frequency domain (FFT). After euthanasia, mesenteric resistance artery (MRA) was dissected out and rings were mounted in an isometric myograph (DMT,620M). MRA responses to noradrenaline (Nor; 0.1nM-1μM) and acetylcholine (Ach; 0.01nM-30μM) were studied. One-way ANOVA and p<0.05 were used for statistical analysis

F induced glucose intolerance (1 copy: 100±3 vs. F=198±5; 2 copies: 121±4 vs. F=201±8; 3 copies: 86±4 vs. F=212±5 mg/dl after 120 min) with no alterations in total cholesterol nor triglycerides. Systolic BP increased in 2 and 3-copy mice after F (1 copy: 119±2 vs. F=124±4; 2 copies: 120±3 vs. F=131±3; 3 copies: 121±3 vs. F=139±4 mmHg) and diastolic BP increased in all F-fed groups (1 copy: 80±2 vs. F=92±3; 2 copies: 83±2 vs. F=95±4; 3 copies: 84±2 vs. F=100±2 mmHg). The augment in systolic BP was significantly higher in 3-copy (17±1 mmHg) vs. 1 (6±1 mmHg) and 2-copy mice (10±1 mmHg). F also increased BP variability in all groups, with a more pronounced augment in 3-copy mice vs. other groups (1 copy: 39±3 vs. F=57±2; 2 copies: 37±2 vs. F=60±3; 3 copies: 40±3 vs. F=73±7 mmHg
2
). Additionally, the sympathetic component of BP variability (LF %) presented a similar behavior (1 copy: 5±1 vs. F=12±3; 2 copies: 6±2 vs. F=19±3; 3 copies: 7±3 vs. F=31±5 %). Ach-induced relaxation was reduced in F mice (1 copy: 78 vs. F=58; 2 copies: 76 vs. F=47; 3 copies: 73 vs. F=36 %) and a hyperreactivity to Nor was also observed (1 copy: 92 vs. F=170; 2 copies: 107 vs. F=190; 3 copies: 101 vs. F=214 %). In both responses, 3-copy mice were significantly different than the other groups.

ACE gene dosage seems to modulate the magnitude of MRA and autonomic dysfunctions caused by F consumption, inducing a more increased cardiovascular risk for 3-copy mice.
Abstract 316: Angiotensin 1-7 Regulation Of Endothelin-1 System In Pulmonary Arterial Hypertension
Authors: Hood Katie Y , Yusuf Hiba , Findlay Jane E , Santos Robson A , Castro Carlos H , Baillie George S S , Montezano Augusto C Montezano C , MacLean Margaret R , Touyz Rhian M
Published: March 2022

Studies suggest that activation of ACE2-Ang-(1-7)-Mas ameliorates vascular, cardiac and lung damage observed in pulmonary hypertension (PAH); a condition where endothelin-1 (ET-1) is important. Here we assessed whether Ang 1-7 regulates ET-1 system in pulmonary hypertension and putative mechanisms. Hypobaric hypoxia was used to induce hypoxic PAH in mice, which were divided in 4 groups: normoxic controls (NC), hypoxic PAH (HP), normoxic (NA) and hypoxic PAH (HA) treated with Ang 1-7 (hydroxypropyl-βcyclodextrin-Ang(1-7) 30μg/kg/day given by oral gavage for 14 days after established hypoxia-induced PAH. In HP mice, RVSP (18.7 NC vs. 47.6mmHg HP, p<0.001), RVH by Fulton Index (0.198 NC vs. 0.279 HP, p<0.01) and urinary ET-1 levels (0.88 NC vs 2.48pg/ml HP, p<0.05 vs NC) were increased, an effect blocked by Ang1-7 treatment. In NA, Ang 1-7 increased urinary levels of ET-1 (2.24pg/ml, p<0.05 vs NC). No changes were observed on ETBR protein expression between all groups. Human microvascular endothelial cells (HMEC) were also used and stimulated with ET-1 in the absence/presence of Ang 1-7. Ang 1-7 stimulation increased preproET-1 mRNA levels (250%), ET-1 release (125%), and ETBR protein levels (50%), p<0.05 vs vehicle. To examine whether the regulation of ET-1 system by Ang 1-7 is beneficial, HMEC were stimulated with ET-1 in the absence/presence of Ang 1-7. ET-1 increased e-selectin mRNA (400%) and VCAM-1 protein (38%) levels, as well as TNFα production (30%); all effects blocked by Ang 1-7 (p<0.05). Ang 1-7 inhibition of ET-1 pro-inflammatory effects was dependent on NO production, since it was blocked by L-NAME and LY294002 (inhibitors of NO pathway). Interestingly, Ang 1-7 increased NO production (257%) through Mas and ETBR-dependent manner. An interaction between Mas and ETbR was observed in HMEC by immunoprecipitation and peptide array protocols. In conclusion, Ang 1-7 modulates ET-1 system in pulmonary hypertension and HMEC. Our findings indicate that Ang 1-7 negatively modulates proinflammatory signalling in human endothelial cells. The protective effect may involve upregulation/crosstalk of/with ETBR. These data identify the ET-1 system as a novel molecular mechanism involved in the putative protective action of Ang 1-7 in pulmonary hypertension.
Abstract 324: Collectrin in The Kidney Determines Salt-Sensitivity
Authors: Chu Pei-Lun , Cechova Sylvia , Chan Rosa , Le Thu H
Published: March 2022

Collectrin (Tmem27), an ACE-2 homologue and a chaperone of amino acid transporters, is expressed in the endothelium throughout the vasculature and in the renal epithelia, including the proximal tubules and collecting duct. Its renal expression is upregulated after reduction of nephron mass and during salt-sensitive hypertension (SSH). These observations raise the question of how collectrin might be functionally integrated in the ACE family in the context of blood pressure (BP) regulation. We previously reported that, on a permissive genetic background, collectrin-deficient (KO) mice have baseline hypertension (HTN) that is ameliorated by supplementation with L-arginine (L-Arg). Furthermore, they have augmented SSH that is corrected by TEMPOL, a superoxide dismutase mimetic. These phenotypes are associated with impaired cellular uptake of L-Arg, impaired endothelial-dependent relaxation, decreased levels of endothelial nitric oxide synthase dimerization (eNOS), and a rightward shift of the pressure-natriuresis relationship. Here, we demonstrate that the activity or dimerization of neuronal NOS (nNOS) in the renal medulla is also significantly decreased in KO mice. To determine the effect of renal versus extra-renal collectrin on BP regulation, we performed renal cross-transplantation (XTP) studies (through a service provided by the Duke O’Brien Center), under normal and high salt conditions, in the following groups: 1) wild-type (WT) mice with WT kidney (WT -> WT), 2) collectrin KO mice with WT kidney (WT -> KO), and 3) WT mice with collectrin KO kidney (KO -> WT). BP was measured by radiotelemetry. Collectrin KO -> WT group displayed a trend towards higher baseline systolic BP (SBP, mm Hg), but did not reach significance (WT -> WT 137.3, WT -> KO 133.5, KO -> WT 142.4, p = not significant, n = 3-5 per group). By paired analysis, all groups had significantly higher SBP on high salt diet (HSD), compared to normal salt diet. However, collectrin KO -> WT group had a statistically significantly higher SBP under HSD (WT -> WT 148.9, WT -> KO 151.6, KO -> WT 168.6, p= 0.037, one way ANOVA). In conclusion, collectrin may regulate BP by influencing renal hemodynamics and/or epithelial sodium handling through its central role in mediating cellular L-Arg uptake.
Abstract 325: Animal Models of Salt-Sensitive Hypertension Show Impaired Renal Sodium Chloride Cotransporter (NCC) Function
Authors: Walsh Kathryn R , Wainford Richard D
Published: March 2022

Aim:
These studies test the hypothesis that norepinephrine (NE) impairs renal NCC regulation to evoke salt-sensitive hypertension in Sprague-Dawley (SD) and Dahl Salt-Sensitive (DSS) rats.

Methods:
SD rats receiving a s.c. saline vehicle or NE (600ng/min) infusion were fed a 0.4% (NS) or high 8% NaCl (HS) diet for 14 days. Naïve DSS rats were placed on a NS or HS diet for 21 days. On day 14 or 21, MAP and peak natriuresis to i.v. hydrochlorothiazide (HCTZ; 2mg/kg) infusion was assessed. Plasma NE was measured and NCC immunoblotting was performed on kidney cortex tissue (N=5/6).

Results:
Excess NE significantly increased MAP and plasma NE levels in NE infused SD rats. A HS diet further increased plasma NE levels and MAP in both NE infused SD and DSS rats. HS intake failed to suppress NCC activity in NE infused SD rats and naïve DSS rats. Impaired NCC expression was shown in NE and HS treated SD rats.

Conclusion:
These findings reveal that NE infusion combined with a high salt diet in a salt-resistant phenotype evokes the physiological responses found in a genetic model of salt-sensitive hypertension. These data from both animal models support a direct role of NE on NCC function and the pathophysiology of salt-sensitivity.
Abstract 330: Blood Oxygen Level Dependent (BOLD) MR evaluation of renal oxygenation is unaffected by water loading in atherosclerotic renovascular disease
Authors: SAAD AHMED , Herrmann Sandra , Glockner James , Lerman Lilach , Textor Stephen
Published: March 2022

Background:
Renal hypoxia is a complex function of post-glomerular medullary blood flow, active solute transport and is considered a major risk element for acute kidney injury. Previous studies indicate that sodium balance, diuretic administration and some drugs affect tissue oxygenation. Water loading in younger subjects lowers medullary deoxyhemoglobin. We sought to evaluate the effects of water loading on the day of BOLD imaging in older subjects undergoing protocol evaluation of atherosclerotic renovascular disease (ARVD).

METHODS:
Inpatient studies were performed in patients with hemodynamically severe ARVD (n=15, Doppler US velocity >270 cm/sec), during 150 mEq Na+ intake and ACE/ARB Rx. Two groups were studied: Group A (n=10) received oral water loading (20 ml/kg), whereas Group B (n=5) had none. Tissue R2* (index of deoxyhemoglobin levels) and fractional kidney hypoxia (medullary estimate) (% of renal coronal area with R2*>20/s) were measured in stenotic kidneys by BOLD-MRI at 3T, before and after IV injection of Furosemide (20gm).

RESULTS:
Cortical R2* and fractional tissue hypoxia were similar for the 2 groups (P =0.6 and 0.7). Both groups reduced cortical R2* and fractional hypoxia after furosemide injection to the same degree. Table

CONCLUSION:
These data demonstrate that water loading on the day of BOLD evaluation in older subjects with ARVD does not materially alter cortical or medullary estimates of oxygenation. Our results extend previous studies indicating that water loading in older individuals fails to alter medullary oxygenation unlike alterations in sodium intake, diuretic administration or blockade of the renin-angiotensin system.
Abstract 332: Retinol-binding Protein 7 (RBP7) Regulates Endothelial Function, Independent of Metabolic Responses in High-fat Diet Fed Mice
Authors: Hu Chunyan , Liu Xuebo , Keen Henry L , Vogel Silke , Faraci Frank M , Sigmund Curt D
Published: March 2022

Peroxisome proliferator-activated receptor gamma (PPARG), a ligand-activated transcription factor, plays a protective role in the endothelium through mechanisms that remain unclear. RBP7 is an intracellular retinoid binding protein belonging to the family of fatty acid-binding proteins (FABP) and is a PPARG target. RBP7 expression was increased 2.6-fold by rosiglitazone (RZ), a PPARG agonist in mouse lung endothelial cells, which was blocked by GW9662, a PPARG antagonist. We hypothesized that the protective effects of PPARG on the endothelium are mediated by RBP7. Studies were performed in: 20-week HFD-fed RBP7-deficient (KO) and wild type (WT) and age-matched chow-fed KO and WT mice. HFD increased fasting glucose in both WT and KO mice compared to chow-fed groups, and caused similar hepatic steatosis. HFD-fed mice were more glucose-intolerant and insulin-resistant compared with chow-fed mice, but there were no differences comparing KO with WT mice. Weight gain in response to HFD was also similar in KO and WT mice. Thus KO and WT mice exhibited similar HFD-induced metabolic dysfunction. Endothelium-dependent relaxation to acetylcholine (Ach) was normal in chow-fed KO mice, but was impaired in carotid artery of HFD-fed KO mice (49±6% KO vs 70±4% WT, p<0.05, 30μM Ach). Endothelial-independent relaxation was similar in all groups. Superoxide production in carotid artery (DHE-fluorescence) was elevated 1.5-fold in HFD-fed KO mice compared with the other 3 groups. Normal relaxation to Ach was restored by anti-oxidant treatment, suggesting HFD causes oxidative stress in the absence of RBP7. Systolic blood pressure was similar in HFD-fed KO and WT mice (110±4 mmHg in KO vs 105±0 mmHg in WT). Because other members of the FABP family facilitate steroid hormone receptor function, we hypothesized that RBP7 may facilitate PPARG function. To initially test this, we examined the cellular localization of an RBP7-GFP fusion protein. In vehicle treated COS7 cells, RBP7 was distributed both in cytoplasm and nucleus. RZ treatment resulted in a robust shift of RBP7 into the nucleus. In conclusion, RBP7 protects the endothelium from HFD-induced oxidative and vascular dysfunction, independent of changes to systemic metabolism.
Abstract 339: Chronic Treatment With Fluoxetine Increases Relaxation Of Rat Resistance Mesenteric Arteries Via Atp-sensitive Potassium Channels Activation
Authors: Pereira Camila A , Ferreira Nathanne S , Mestriner Fabíola L , Resstel Leonardo L , Carneiro Fernando S , Tostes Rita C
Published: March 2022

Fluoxetine, a selective serotonin reuptake inhibitor (SSRI) has properties that go beyond its antidepressant effects and alters mechanisms involved in the regulation of vasomotor tone. While there are many studies demonstrating the acute effects of fluoxetine in the vasculature, studies on the chronic effects of this SSRI are still limited. Here we postulated that chronic treatment with fluoxetine enhances vascular reactivity to vasodilator stimuli by increasing nitric oxide (NO) signaling. The effects of chronic treatment with fluoxetine on vascular reactivity were determined in resistance mesenteric arteries from Wistar rats, which were treated with (I) vehicle (water for 21 days) or (II) fluoxetine (10 mg/kg/day for 21 days in the drinking water). Fluoxetine treatment increased endothelium-dependent (pEC50, Veh = -7.08±0.07; Fluox = -7.4±0.11, p<0.05) and -independent relaxant response (pEC50, Veh = -7.75±0.08; Fluox = -8.5 ± 0.11, p<0.05). Fluoxetine also increased vascular NOx (NO metabolites) levels (Veh = 1.2±0.13 μM/μg; Fluox = 2.0 ± 0.13 μM/μg, p <0.05), nitric oxide sintase (NOS) activity (Fluox = 76%) and phosphorylation of endothelial NOS (eNOS) at serine1177 [arbitrary units (a.u.), Veh = 0.36±0.10; Fluox = 1.2 ± 0.08, p <0.05]. Fluoxetine treatment did not change neuronal NOS (nNOS) or soluble guanylate cyclase (sGC) expression neither vascular responses to cyclic guanosine monophosphate (cGMP) or sGC activators. However, pinacidil- (KATP channels activator)-induced relaxation was increased by fluoxetine treatment (pEC50, Veh = -5.9±0.12; Fluox = -6.5±0.17, p>0.05). In conclusion, chronic treatment with fluoxetine increases endothelium-dependent and -independent relaxation response in resistance mesenteric arteries by mechanisms that involve increased NOS activity, NO generation and KATP channels activation. These effects may contribute to the cardiovascular side effects associated with fluoxetine treatment.
Abstract 340: Novel Molecular Mechanisms Involved In VEGFR Inhibition In Human Endothelial Cells
Authors: SMALL HEATHER Y
Published: March 2022

VEGF/VEGFR inhibitors are increasingly being used as anti-angiogenic drugs to treat cancer. However these drugs are limited by the development of severe hypertension. Molecular mechanisms whereby VEGF inhibitors cause hypertension are unclear, but nitric oxide (NO) signalling may be involved. We questioned whether reactive oxygen species (ROS) and Ang II, important regulators of vascular function in hypertension, also play a role in VEGF inhibitor-induced vascular dysfunction. Human microvascular endothelial cells (HMECs) were stimulated with vatalanib (VAT-VEGFR inhibitor) and gefitinib (GEF-EGFR inhibitor) in the absence/presence of Ang II. Activation of eNOS and MAPKs were assessed by immunoblotting. Antioxidant enzyme mRNA was analyzed by qPCR. Phosphorylation of eNOS activation site (Ser1177) (28.3% ± 7.1) and p38 MAPK (55.4% ± 2.4) was decreased by VAT, while no changes were observed after exposure of HMECs to GEF (p<0.05). VAT also decreased mRNA expression of Nox4 (0.5 ± 0.2), and H2O2-related antioxidants enzymes such as catalase (0.4 ± 0.1) and glutathione peroxidase (0.4 ± 0.1). Ang II stimulation increased eNOS (171.2% ± 17.4), ERK1/2 (177.5% ± 38.5), p38 MAPK (186.9% ± 36.6) activation (p<0.05); an effect blocked by VAT and GEF. Inhibition of VEGFR also blocked Ang II effects on SOD1 (1.33 ± 0.1), HO-1 (1.6 ± 0.3) and NQO1 (1.6 ± 0.3) mRNA levels (p<0.05). In addition, Ang II increased Nox4 mRNA expression through VEGFR-dependent mechanisms. Interestingly, VEGFR1/2 and AT2R were expressed in HMEC, but not AT1R. Ang II effects on eNOS phosphorylation were inhibited by PDE123 (AT2R antagonist) but not by losartan (AT1R antagonist). In conclusion, our data elucidate novel mechanisms whereby AngII, possibly through AT2R-dependent VEGFR transactivation, regulates eNOS activation, MAPK signalling and H2O2-related antioxidant enzymes. In addition to changes in NO availability, VEGFR inhibition may interfere with the redox status of endothelial cells, leading to vascular dysfunction and hypertension.
Abstract 343: Endothelin-1 Overexpression Preserves Endothelial Function In Mice With Vascular Smooth Muscle Cell-specific Deletion Of Ppar-gamma
Authors: IDRIS KHODJA Noureddine , Ouerd Sofiane , Barhoumi Tlili , Trindade Michelle , Gornitsky Jordan , Rehman Asia , Offermanns Stefan , Gonzalez Frank J , Paradis Pierre , Schiffrin Ernesto L
Published: March 2022

Objective:
Peroxisome proliferator activated receptor γ (PPARγ) agonists reduce blood pressure (BP) and vascular injury in hypertensive rodents and humans.
Pparγ
inactivation in vascular smooth muscle cells (VSMC) using a tamoxifen inducible Cre-Lox system enhanced angiotensin II-induced vascular remodeling and endothelial dysfunction. Transgenic mice overexpressing endothelin (ET)-1 selectively in the endothelium (eET-1) exhibit endothelial dysfunction, increased oxidative stress and inflammation. We hypothesized that inactivation of the
Ppar
gene in VSMC (sm
Pparγ
-/-
) will exaggerate ET-1-induced vascular damage.

Methods:
Eleven week-old male control, eET-1, sm
Pparγ
-/-
and eET-1/sm
Pparγ
-/-
mice were used. BP by telemetry, mesenteric artery (MA) reactivity and structure by pressurized myography, reactive oxygen species (ROS) by dihydroethidium (DHE) staining and fibronectin expression by immunofluorescence were determined.

Results:
Systolic BP was higher in eET-1 and eET-1/sm

Pparγ
-/-

compared to control and sm

Pparγ
-/-

(127±3 and 124±7 vs 109±2 and 114 ± 4 mmHg, respectively,
P
<0.05). Endothelium-dependent relaxation (EDR) responses to acetylcholine were impaired in sm
Pparγ
-/-
(
P
<0.05) but not in eET-1 and sm
Pparγ
-/-
/eET-1 compared with control (E
max
: 52.0±6.7%, 66.2±7.6 and 87.1±4.4% vs 82.2±4.9%). Endothelium-independent relaxation responses to the nitric oxide donor, sodium nitroprusside, were similar in the four groups. Media/lumen at 45 mmHg was higher only in eET-1/sm

Pparγ
-/-

compared with control (5.5±0.21 vs 4.5±0.21,
P
<0.05). Increased stiffness was observed in eET-1, sm

Pparγ
-/-

and eET-1/sm

Pparγ
-/-

compared to control, as indicated by a leftward displacement of the stress-strain curves (strain at 140 mmHg: 0.82±0.03, 0.81±0.04, 0.80±0.03 vs 0.97±0.02,
P
<0.05). ROS levels were increased 1.7±0.2 fold in eET-1, 2.2±0.2 fold in sm

Pparγ
-/-

and 2.8±0.4 fold in eET-1/sm

Pparγ
-/-

compared with control (
P
<0.05). Fibronectin staining in MA was similar in the four groups.

Conclusion:
These results suggest that increased ET-1 paradoxically preserves endothelial function in mice with inactivated
Pparγ
in vascular smooth muscle, despite presence of enhanced oxidative stress.
Abstract 347: Comparative Study of Cardiovascular Morphology in Hypertensive, Insulin Resistant and Middle-aged Rats
Authors: Burlá Adriana K , Neves Mario F , Oigman Wille
Published: March 2022

The objective of this study was to compare the effect of insulin resistance, hypertension and aging on cardiac fibrosis and intramyocardial arteries (IMA). Twenty eight male rats were divided into four groups: control (CON), insulin resistance induced by monosodium glutamate (MSG) administered in neonatal period, spontaneously hypertensive rats (SHR), middle-aged rats (MAR). The first three groups were 22 weeks-old and the older group was 30 weeks-old. The heart was fixed and stained with picro Sirius red to evaluate myocardial collagen density. The lumen diameter, media thickness and media cross- sectional area (CSA) of the IMA were measured with the Image Pro Plus image analysis software. The Lee index was slightly increased in MSG group. The systolic blood pressure was significantly elevated in SHR group (CON 113±2, MSG 122±3, SHR 202±3, MAR 115±3 mmHg). The diameter of the IMA was significantly smaller in SHR (29.8±2.4 μm, p<0.01) vs MAR (35.3±2.2 μm), CON (34.0±2.3 μm) and MSG (34.7±2.4 μm). The media-to-lumen ratio was 29.5 ± 1.2% in CON, 39.8 ± 1.3% in MSG, 30.3 ± 0.6% in MAR and 46.5 ± 4.0% in SHR (P<0.001 vs CON/ MAR, P<0.01 vs MSG). The CSA of IMA was significantly increased in SHR and MSG compared to CON showing growing index of 38.5 and 33.0%, respectively. Interstitial subendocardial collagen density of the left ventricle was 2.8±.0.3% in CON, 3.1±.0.7% in SHR, 2.6±0.6 in MAR and 4.0±.0.8% in MSG (P<0.05 vs SRH, P<0.01 vs CON and MAR).The perivascular collagen density was greater in MSG group (48.4±.2.3%, p<0.001 vs other groups) but was also significantly increased in SHR (42.6±.2.3%) and MAR (36.4±1.4 %) groups compared to CON (29.8±.3.0%, p<0.01). In conclusion, hypertrophic vascular remodeling was more associated to hypertension while cardiac fibrosis was more observed when insulin resistance and obesity were present. There were no significant cardiovascular changes in older animals without hypertension and insulin resistance.
Abstract 353: Castration Impairs Rat Internal Pudendal Artery Reactivity And Structure
Authors: Lopes Rheure A , Neves Karla B , Silva Marcondes , Olivon Vania , Ruginsk Silvia , Ramalho Leandra , Antunes Jose , Tostes Rita , Carneiro Fernando S
Published: March 2022

Testosterone deficiency is strongly associated with erectile dysfunction (ED). Inadequate penile arterial flow is one of the major causes of ED. Considering that blood flow to the corpus cavernosum is derived from the internal pudendal arteries (IPA), we hypothesized that castration induces impairment of IPAs reactivity and structure, contributing to ED. Male Wistar rats were studied 30 days after castration (Cast). Functional and structural properties of rat IPA were determined in wire and pressure myograph systems, respectively. Castrated rats exhibited impaired erectile function, represented by decreased intracavernosal pressure/mean arterial pressure ratio [ICP/MAP (sham = 0.5 ± 0.1; castrated = 0.2 ± 0.1; 20 Hz. p <0.05)]. Castrated rats exhibited decreased phenylephrine (Phe)- [(% Kcl) Control: 175.4 ± 4.6 vs Cast: 134,9 ± 11; Emax] and electrical field stimulation (EFS)-induced contraction [(% Kcl) Control: 213,0 ± 7.1 vs Cast: 137 ± 6.1; 12Hz] and decreased acetylcholine (ACh)- (Control: 79.7 ± 2.2 vs Cast: 49.8 ± 2.8; Emax) and EFS-induced vasodilatation (Control: 54.6 ± 2.1 vs Cast: 35.5 ± 1.6; 12hz). IPAs from Cast rats exhibited decreased internal diameter [Control (μm): 499.9 ± 35.9 vs Cast: 413.0 ± 14.8; 60 mmHg], external diameter [Control (μm): 669.4 ± 40.1 vs Cast: 552.0 ± 30.0; 60 mmHg], thickness of the arterial wall [Control (μm): 81.2 ± 6.4 vs Cast: 55.8 ± 7.5; 80 mmHg] and cross-sectional area [Control (μm2): 157217 ± 12533 vs Cast: 116383 ± 12424; 30 mmHg]. Castration decreased nNOS expression (60%) and increased p38 (Thr180/Tyr182) phosphorylation (450%), as well as cleavage of caspase 3 (270%). In conclusion, testosterone deficiency is associated with impairment of IPA reactivity and structure and increased apoptosis signalling markers. Our findings suggest that hypogonadism may contribute to IPA dysfunction, which can leads to ED. Financial support: FAPESP and CNPq.
Abstract 354: Vascular Oxidative Stress Promotes Aortic Stiffening In Hypertension
Authors: Wu Jing , Saleh Mohamed A , Kirabo Annet , Itani Hana , Chen Wei , Madhur Meena S , Harrison David G
Published: March 2022

We have previously shown that T cells and the cytokine IL-17a contribute to aortic stiffening in hypertension. Because oxidative stress also contributes to hypertension, we sought to determine if chronic oxidative stress causes aortic stiffening and to determine if T cells are involved. We studied tgsm/p22phox mice, which have an overexpression of the NADPH oxidase subunit p22phox in the vascular smooth muscle and approximately 2-fold increase vascular reactive oxygen species (ROS). Six month-old tgsm/p22phox mice were normotensive at baseline but exhibited increased aortic stiffness as indicated by the leftward shift of stress-strain curves (p<0.05). Aortic collagen content, as determined by hydroxyproline assay, was also increased in these mice compared to age-matched C57Bl/6 mice (76.3±11.9 vs. 43.2±11.9 ng/μg total protein, p<0.01). At nine months of age, aortic stiffening did not further increase but tgsm/p22phox mice developed vascular inflammation and mild hypertension (137±9 systolic and 100±7 diastolic, p<0.05), indicating that aortic stiffening precedes hypertension. Surprisingly, T cells isolated from the spleen of 9 month-old Tgsm/p22phox mice demonstrated marked production of IL-17a and IFN-gamma. To determine if inflammation contributes to these pathological events, we crossed the tgsm/p22phox mice with RAG-1-/- mice. The resultant mice were protected from vascular inflammation, aortic stiffening and hypertension. Tempol, a superoxide dismutase mimetic, normalized blood pressure (109±4 systolic and 95±4 diastolic, p<0.05), reduced vascular collagen deposition (37.5±9.5 ng/μg total protein, p<0.01) and prevented aortic stiffening in tgsm/p22phox mice. We have recently shown that isoketals, which are oxidation products of arachidonic acid, promote T cell activation. Treatment with the isoketal scavenger 2-hydroxybenzylamine also normalized blood pressure, prevented collagen deposition and aortic stiffening in 9 month-old tgsm/p22phox mice. These data are compatible with a pathway in which vascular oxidative stress leads to formation of isoketals, which promote T cell activation, production of cytokines such as IL-17a and IFN-gamma, which in turn promote collagen deposition and aortic stiffening.
Abstract 403: MicroRNA-21 Ablation Exacerbates Aldosterone-mediated Cardiac Inflammation, Fibrosis, Hypertrophy and Dysfunction
Authors: Syed Maryam , Ball Jana P , Mathis Keisa W , Hall Michael E , Ryan Michael J , Rothenberg Marc E , Romero Damian G
Published: March 2022

Excess aldosterone (ALDO) causes hypertension and cardiac hypertrophy, inflammation and fibrosis that lead to cardiac dysfunction. We reported that ALDO/SALT treatment increases left ventricle miR-21 expression after 2 weeks of treatment, and the elevation persists for up to 8 weeks. We aim to study the role of genetic ablation of miR-21 in ALDO/SALT-mediated cardiac inflammation, fibrosis, hypertrophy and function.

Eight-week old uninephrectomized male miR-21 knockout (miR21KO) or wild-type (WT) mice were assigned to 4 groups (N=12/grp): WT-Control, WT-ALDO/SALT, miR21KO-Control and miR21KO-ALDO/SALT. Animals were treated for 8 weeks. ALDO (0.15 μg/h) or vehicle (PEG 300) was administered by osmotic minipump. SALT (1.0% NaCl + 0.3% KCl) was administered in tap water. Cardiac function was determined by echocardiography. Tissues were weighed and standardized to body weight. mRNA levels were quantified by qPCR. Another set of animals (N=12/grp) was implanted with carotid artery catheters for conscious MAP determination.

ALDO/SALT-mediated cardiac dysfunction was exacerbated in miR21KO mice (EF: 38.0 ± 2.0 vs. 43.0 ± 4.1 %,
p
<0.05) compared with WT mice (EF: 50.0 ± 3.7 vs. 54.7 ± 3.1 %, NS). ALDO/SALT-mediated cardiac hypertrophy was exacerbated in miR21KO mice compared with WT mice (ALDO-SALT/control: 1.30 ± 0.04
vs
. 1.18 ± 0.02,
p
<0.05).

Fibrosis marker connective tissue growth factor (Ctgf) mRNA expression remained elevated by ALDO/SALT only in miR21KO mice (7.22 ± 1.96 fold change
vs
. control,
p
<0.05). Similar results were observed with collagen I and fibronectin. Inflammation marker Serpine1 (PAI-1) mRNA expression was upregulated by ALDO/SALT only in miR21KO mice (3.11 ± 0.54 fold change
vs
. control,
p
<0.05).

Despite the exacerbation in cardiac dysfunction, hypertrophy, and fibrosis and inflammation markers expression in miR21KO mice, ALDO/SALT raised MAP to similar levels in both strains (WT: 139 ± 9
vs
. 106 ± 2 mm Hg,
p
<0.05; miR21KO: 142 ± 8
vs
. 114 ± 4,
p
< 0.05).

These results show that miR-21 ablation exacerbates ALDO/SALT-mediated cardiac inflammation, fibrosis, hypertrophy and dysfunction independently of blood pressure suggesting that therapies that increase cardiac levels of miR-21 may benefit patients with primary aldosteronism.
Abstract 404: Racial Differences In Aldosterone And Its Relationship With Potassium
Authors: Tu Wanzhu , Eckert George , Pratt John Howard
Published: March 2022

Potassium (K), acting synergistically with angiotensin-II, stimulates aldosterone production, which then promotes secretion of K in distal nephron. Blacks have on average significantly lower aldosterone levels than whites. The extent to which the reduced aldosterone level stems from less stimulation by K is unknown. Also, there may be less dependency on aldosterone to influence K homeostasis in blacks. In an observation study, we looked for race differences in K-aldosterone relationships in a cohort of healthy young blacks and whites (ages 5-39 years). We analyzed 1116 samples from 161 blacks and 271 whites. Our data showed that at although K decreased with age (at a rate of 0.09 mmol/L per year), at any given age K levels of blacks and whites were quite similar (Fig a & b), whereas plasma aldosterone levels were approximately 7 ng/dL lower in blacks (p<0.0001; Fig c & d). We then assessed the aldosterone-K relationships by characterizing the effects of K on aldosterone as functions of age. K and aldosterone were positively correlated in both race groups (p<0.0001), an effect that declined with age for both groups (p<0.05), but at any given age K effect was significantly greater in whites (p<0.001; Fig e and f). Blacks maintained K at a level that was nearly identical to whites despite their having much lower aldosterone levels. We speculate that an expanded volume in blacks facilitated K excretion and reduced stimulation of aldosterone by K because of less synergism with angiotensin II. With increasing age additional sodium may accumulate which increases volume resulting in concurrent declines in K, aldosterone, as well as their associations, in both race groups.
Abstract 406: Direct Angiotensin AT2-Receptor Stimulation Modifies T-Cell Differentiation
Authors: Sehnert Bettina , Valero-Esquitino Veronica , Cirera-Salinas Daniel , Lucht Kristin , Pascual Anna , Curato Caterina , Voll Reinhard , Unger Thomas , Steckelings Ulrike M
Published: March 2022

Angiotensin II is known to activate T-cells via the AT1-receptor. T-cells also possess AT2-receptors (AT2Rs). However, the functional role of AT2Rs in T-cells has not been investigated.

This study tested the hypothesis that AT2R stimulation modulates T helper (Th) cell differentiation. For this purpose, naïve T-cells were isolated from spleen and lymph nodes of C57BL/6 mice, sorted, polarized in vitro under Th0, Th1, Th17 and regulatory T-cell (Treg) conditions and simultaneously treated with the AT2R agonist C21 (1μM) or vehicle for 4 days.

24 hours after the last treatment, expression of cytokines characteristic for pro-inflammatory Th1 cells (IFNγ) and Th17 cells (IL-17), or anti-inflammatory Treg (FoxP3) were determined on mRNA (qRT-PCR) and protein (FACS analysis) level.

AT2R stimulation during polarization of naïve T-cells decreased mRNA levels of IFNγ (in TH1 polarized T-cells: 2.2±0.4x105 [vehicle] versus 0.1±0.001x105 [C21] fold increase; p<0.05), IL-17 (in TH17 polarized T-cells; 572.1±149.0 [vehicle] versus 296.1±54.4 [C21] fold increase; p<0.05) and increased mRNA levels FoxP3 (in Treg polarized T-cells: 101.9±16.1 [vehicle] versus 342.5±12.4 [C21] fold increase; p<0.05).

Similar results were obtained for protein expression of IFNγ (6.5±0.5x105 [vehicle] versus 4.0±0.7x105 [C21] cells; p<0.05), IL-17 (1.2±0.1x105 [vehicle] versus 0.9±0.1x105 [C21] cells; p=0.06 and FoxP3 (1.5±0.5x105 [vehicle] versus 3.7±0.6x105 [C21] cells; p<0.05).

From our data we conclude that AT2R stimulation modifies T-cell differentiation resulting in a composition of T-cell subsets with less pronounced pro-inflammatory properties.
Abstract 410: Multimorbidity, Medication Adherence And Blood Pressure Control Among Hypertensive Patients In Primary Care Settings
Authors: Wong Martin C , Wang Harry H , Liu Kirin Q , Chan Wai Man , Kwan Mandy W , Zhang Daisy D , Lao Xiang Qian
Published: March 2022

Background:
Multimorbidity, defined as having more than one co-existing chronic condition, induces substantial disease burden. This study aimed to evaluate whether multimorbidity is associated with poor medication adherence and poor blood pressure (BP) control.

Methods:
A multistage, cluster random sampling was adopted to recruit adult hypertensive patients attending general outpatient clinics in Hong Kong in 2012. Data on BP and the number of chronic medical conditions were collected onsite using a standardised protocol. Adherence to medication was assessed by Morisky Medication Adherence Scale (MMAS-8). A binary logistic regression analysis was conducted with multimorbidity as the outcome variable, and poor adherence (MMAS-8 score ≤ 6) and suboptimal BP control (SBP/DBP > 130/80 mmHg for those with diabetes or chronic kidney disease; and > 140/90 mmHg for others) were included as covariates.

Results:
From a total of 1,445 completed surveys, the proportion of hypertensive patients having 0, 1 and ≥ 2 additional conditions was 53.6% [775/1,445], 37.5% [542/1,445] and 8.9% [128/1,445]. The corresponding rate of poor adherence was 54.3% [379/698], 37.2% [260/698], and 8.5% [59/698], whereas the rate of suboptimal BP control was 48.0% [294/613], 41.3% [253/613], and 10.8% [66/613], respectively. When compared with patients with no additional conditions, multimorbid patients were significantly more likely to have suboptimal BP control (AOR= 1.47, 95% CI 1.18-1.84, p < 0.001).

Conclusions:
Multimorbidity was common among hypertensive patients, and was associated with poor BP control. They should receive more clinical attention to achieve better clinical outcomes.
Abstract 417: Correlation Between The Mass Of The Left Ventricle By Echocardiogram And The Electrocardiographic And Vectorcardiographic Criteria In Left Ventricular Hypertrophy In Patients With Resistant Hypertension.
Authors: Dinamarco Nelson , Dinamarco Marileide , Moreno Heitor
Published: March 2022

The difficult of most of patients in access the echocardiogram (ECHO) diagnosis services are common in small cities located far away from reference towns centers. Graphics methods (GM) , like electrocardiogram (ECG) and vectorcardiogram (VCG), have high sensibility but low specificity in detect LVH. The ECHO diagnosis criterion of LVH based on indexed left ventricular mass (LVMI), is usual and used now a days beside other methods like Nuclear Magnetic Ressonance.

Objectives:
Evaluate LVMI correlation with ECG and VCG criteria in patients with RHTN.

Population:
120 RHTN patients were evaluated. Excluded patients with diseases: diabetes, valve heart, coronary, Chagas, renal, obese and excentric LVH.

Study Protocol:
After 06 months, between 2008& 2011, measures BP monthly following the technique (JNC-VII) and receive directions, as well as pill counts (the method of Taylor) to assess compliance. Underwent echocardiography, following the recommendations of the ASE, then ECG and VCG. Formula to calculate LVMI : LVMI = 0,8 x{1.04x [(SIVD + DDVE + PPVED)3 - (DDVE)3]} + 0,6 g/(M-60) x 0,01 + H) ECG and VCG criteria to detect LVH: ECG Criterion: Sokolow-Lyon I(SL-I):SV1+RV5(6)≥3.5mV & II(SL-II):RavL≥1.1mV; Gübner(G):SDI+RDIII≥2.5mV; Cornell(C):RavL+SV3≥2/2.8mV(woman/man); Romhilt-Estes(RE):Point Score≥5points; Perugia(P): RE or C(modify) or Strain. VCG Criterion: Mag Max QRS on Planes horizontal(HP) & frontal(FP): vector≥2mV and right saggital(rSP): vector≥1.6 mV; Defl QRS HP & rSP: angle≥ 330° & ≥150°.

Statistical Analysis:
The correlations were obtained using the Pearson’s correlation formula and the is considered a good correlation values above 50%, and excellent correlation values above 70%. Values less than 50% are considered weak correlation. Results are expressed as mean and standard deviation, and relative values in percentage.

Results:
Criterion Correlation R

SL- I 0.49

G 0.42

SL-II 0.50

C 0.49

RE 0.51

Mag Max QRS HP 0,59

Mag Max QRS rSP 0.60

Mag Max QRS FP 0.51

Defl QRS PH 0.33

Defl QRS rSP 0.56

Conclusion:
The better correlation between LVMI and ECG criterion was Romhilt-Estes and the better for the VCG was Mag Max QRS HP. The VCG had the best correlation. Considered a good alternative to estimate the LVMI.