Abstract 2474: Rho-Kinase Inhibition Improves Endothelium-Dependent Vasodilation during Hyperinsulinemia in Patients with Metabolic Syndrome

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Francesca Schinzari ◽  
Manfredi Tesauro ◽  
Valentina Rovella ◽  
Augusto Veneziani ◽  
Nadia Mores ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Rho Kinase ◽  
Serine Phosphorylation ◽  
No Donor ◽  
Kinase Inhibition ◽  
Impaired Insulin

Impaired insulin-mediated vasodilation in the skeletal muscle may be involved in the development of hypertension in patients with metabolic syndrome (MetS) and contribute to insulin resistance by diminishing the glucose uptake. Rho-kinase, an effector of the small G protein Rho A, plays an important role in hypertension and is reported to interfere with insulin signaling through serine phosphorylation of insulin receptor substrate-1 in blood vessels. We therefore examined the role of Rho-kinase in the pathophysiology of impaired vascular reactivity in patients with MetS by evaluating the effect of Rho-kinase inhibition on NO-dependent vasodilation during hyperinsulinemia. Forearm blood flow (FBF) responses to acetylcholine (ACh), a stimulus for endothelial release of NO, and sodium nitroprusside (SNP), an exogenous NO donor, were assessed during insulin administration (0.1 mU/Kg/min) using the forearm perfusion technique in patients with MetS (n=10) and matched controls (n=10). Patients with MetS were then randomized to intra-arterial infusion of either fasudil (inhibitor of Rho-kinase, 200 μg/min) or placebo and reactivity to ACh and SNP was reassessed. During hyperinsulinemia, vasodilator responses to both ACh and SNP were blunted in patients with MetS (both P>0.001 vs. controls). In patients who received fasudil, its administration did not change unstimulated FBF (P=0.75 vs. insulin alone); the vasodilator response to ACh, however, was significantly enhanced by fasudil (P=0.009 vs. insulin alone), while the response to SNP was not significantly changed (P=0.56). In patients with MetS who received placebo, vascular reactivity to both ACh and SNP was not different than before (both P>0.05). In conclusion, Rho-kinase inhibition during hyperinsulinemia improves endothelium-dependent vasodilator responsiveness in patients with MetS. This suggests that, under those conditions, intravascular activation of Rho-kinase is involved in the pathophysiology of endothelial dysfunction and may constitute a critical mediator linking metabolic and hemodynamic abnormalities in insulin resistance. As a consequence, targeting Rho-kinase might beneficially impact both vascular function and insulin sensitivity in patients with MetS.

Abstract 138: Altered Vascular Reactivity in Mice Overexpressing Adipocyte Mineralocorticoid Receptors - Role of Rho Kinase.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Aurelie Nguyen Dinh Cat ◽  
Tayze T Antunes ◽  
Glaucia E Callera ◽  
Augusto C Montezano ◽  
Ying He ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Molecular Mechanisms ◽  
Rho Kinase ◽  
Mesenteric Arteries ◽  
Mineralocorticoid Receptors ◽  
Resistance Arteries ◽  
Brown Adipose

Aldosterone (aldo) plays a role in cardiovascular diseases, including hypertension and obesity. We previously demonstrated that adipocyte-derived factors regulate vascular function and cell signaling in cultured vascular smooth muscle cells. Moreover, adipocytes are able to produce aldo, which influences vascular reactivity. Plasma levels of aldo are positively correlated with obesity and hypertension. However, the pathophysiological role of aldo and mineralocorticoid receptors (MR) in adipose tissue and its interactions with the vasculature remains elusive. In our study, we investigated molecular mechanisms whereby activation of MR, in adipocytes, leads to release of vascular reactive factors and regulation of vascular tone, using a conditional transgenic mouse model that overexpresses MR only in the adipocytes. Vascular reactivity of resistance mesenteric arteries to acetylcholine (Ach), sodium nitroprusside and phenylephrine (Phe), in the absence or presence of fat conditioned medium (Fcm) from control and adipocyte overexpressing MR (DT) mice, was performed by myography. In basal conditions, endothelial dysfunction was not observed in DT or control mice. However, in the presence of Fcm from DT mice, relaxation to Ach was impaired in control mice (Ach 10 -6 M: 77.5±9.6% no Fcm vs. 49.8±7.5% Fcm, p<0.05), an effect blocked by N-acetyl-cysteine (anti-oxidant) (Ach 10 -6 M: 82.2±6.6%). Resistance arteries from DT mice had decreased Phe-induced contraction, compared to control mice (Phe 10 -5 M: 2.7±0.2 mN/mm CT vs. 1.7±0.2 mN/mm DT, p<0.05). Phosphorylation of ezrin, a marker of Rho kinase activation, measured by immunoblotting, was decreased in white and brown adipose tissues of DT (CT: 3.1±0.7 vs. DT: 0.6±0.1, arbitrary units, p<0.05). In conclusion, MR in adipocytes may play an important role in the regulation of vascular function, and may be involved in vascular oxidative stress. MR in adipocytes is also important to the anti-contractile properties of the adipose tissue through downregulation of Rho kinase signaling. Our study identiy novel mechanisms linking vascular and adipose biology through adipocyte MRs.

scholarly journals Myocardial remodeling in rats with metabolic syndrome: role of Rho-kinase mediated insulin resistance.

2012 ◽  
Vol 59 (2) ◽  
Author(s):  
Chuan-Bao Li ◽  
Xiao-Xing Li ◽  
Yu-Guo Chen ◽  
Hai-Qing Gao ◽  
Cheng-Mei Bao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Critical Role ◽  
Rho Kinase ◽  
Myocardial Damage ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Protein Levels ◽  
Transmission Electron ◽  
And Function

Insulin resistance (IR) plays a critical role in metabolic syndrome (MS). Previous studies have demonstrated that activated ROCK is increased in MS patients. However, the effect of Rho-kinase (ROCK) on IR has not been definitely determined. Thus, the aims of the present study were to determine whether ROCK activation induces IR or affects myocardial structure and function, as well as the possible mechanisms underlying this process. Wistar rats fed high fat, high glucose and high salt diet sewed as model of MS and we used transmission electron microscopy, echocardiogram technology, and terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling staining to identify any myocardial damage. The protein levels of MYPT-1 (characteristic of ROCK activation), IRS-1 and AKT were analyzed by immunohistochemistry and Western blotting. In hearts from MS rats, we found increased protein levels of phospho-MYPT-1 and phospho-IRS-1 (Ser307) and decreased phospho-AKT compared to levels in normal rats. In conclusion, the results suggest that ROCK-mediated IR is involved in the development of myocardial impairments in MS rats and that this effect is mediated probably via the IRS-1/PI3-kinase/AKT pathway.

Abstract 372: Upregulation of the Mineralocorticoid System in Obesity-associated Diabetes Leads to Increased Adipocyte Rho Kinase Activation and Dysregulation of Adipocytokines

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Aurelie Nguyen Dinh Cat ◽  
Glaucia E Callera ◽  
Tayze T Antunes ◽  
Augusto C Montezano ◽  
Ying He ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Vascular Function ◽  
Rho Kinase ◽  
Mrna Levels ◽  
Rock Inhibitor ◽  
Perivascular Adipose Tissue ◽  
Kinase Activation ◽  
Downstream Signaling ◽  
Protein Levels

Increased activation of the renin-angiotensin-aldosterone (RAAS) system is often associated with obesity and metabolic syndrome. We previously reported that aldosterone (aldo) produced by adipocytes regulate vascular function. Despite the fact that aldo production by adipocytes is increased in obesity, the role of aldo and its receptor, the mineralocorticoid receptor (MR), in the regulation of adipocytes biology and their downstream signaling remain elusive. Since Rho kinase (Rock) signaling has recently been implicated in the development of obesity, we tested the hypothesis that MR upregulation leads to dysregulation of adipokines through Rock-dependent mechanisms in obesity. Here we used obese db/db and lean db/+ mice, treated for 4 weeks with K canrenoate (MR antagonist, 30 mg/kg/day) and fasudil (Rock inhibitor, 30 mg/kg/day). Aldo production and Rock activation were measured by ELISA. mRNA and protein levels of adipokines and Rock signaling were assayed by real time PCR and immunoblotting. Plasma and adipocyte-derived aldo levels were increased in db/db mice (plasma: pg/mL, db/+ 310±33, db/db 567±43, p<0.05; adipocytes: pg/mL/μgRNA, db/+ 329±130, db/db 3125±494, p<0.002), an effect partially prevented by MR blockade (pg/mL/μgRNA: db/db 1278±176, p<0.01) and not by fasudil. Aldosterone synthase mRNA levels were increased (2.3 fold) as well as Nr3c2 (MR) (1.8 fold) and markers of MR activation ( Sgk1 and Ngal - 2.3 and 2.9 fold) in mature adipocytes from db/db mice. In mature adipocytes from db/db, adiponectin mRNA levels were decreased (2.6 fold; p<0.01), whereas leptin and IL-6 mRNA levels were increased (2 and 4.8 fold; p<0.01). All changes were blocked by K canrenoate. Rock activity and downstream effectors, such as activation of MYPT1 and ERM, were increased in perivascular adipose tissue from db/db mice, an effect prevented by MR blockade. In conclusion, our data demonstrate that in db/db mice adipocyte MR-dependent activation of Rock is associated with a pro-inflammatory adipose phenotype that is normalized by MR blockade. Our results implicate a potential role of adipocyte aldo/MR through RhoA/Rock in adipocyte dysfunction in obesity/diabetes, important co-morbidities often associated with metabolic syndrome and hypertension.

scholarly journals The Potential Role of Irisin in Vascular Function and Atherosclerosis: A Review

2020 ◽  
Vol 21 (19) ◽  
pp. 7184
Author(s):  
Kyeongho Byun ◽  
Sewon Lee
Keyword(s):  
Insulin Resistance ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Potential Role ◽  
Metabolic Diseases ◽  
Vascular Complications ◽  
Signaling Mechanism ◽  
Vascular Abnormalities ◽  
Treatment Of Obesity

Exercise is an effective intervention for both the prevention and the treatment of obesity and insulin resistance because skeletal muscle secretes many bioactive proteins that contribute to the beneficial effect of exercise. It has been revealed that irisin plays an important role in metabolic homeostasis and both acute and chronic exercises increase circulating irisin in experimental animal models and in humans. Although previous studies have reported that the irisin-related signaling mechanism may play a beneficial role in the treatment of metabolic diseases including obesity, metabolic syndrome, insulin resistance, and diabetes mellitus, studies on whether irisin plays a key role in vascular function and vascular complications are still insufficient. Therefore, the current review aims to summarize the accumulating evidence showing the potential role of irisin, especially in vascular reactivity and vascular abnormalities such as atherosclerosis.

Abstract 66: Altered Vascular Reactivity in Mice Overexpressing Adipocyte Mineralocorticoid Receptors - Role of Oxidative Stress and Rho Kinase

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Aurelie Nguyen Dinh Cat ◽  
Glaucia E Callera ◽  
Tayze T Antunes ◽  
Augusto C Montezano ◽  
Ying He ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Vascular Dysfunction ◽  
Rho Kinase ◽  
Mesenteric Arteries ◽  
Resistance Arteries ◽  
Tissue Interactions

Aldosterone (aldo) plays a role in obesity and cardiovascular diseases, such as hypertension. We previously demonstrated that adipocyte-derived factors regulate vascular function and vascular smooth muscle cells signaling. Moreover, adipocytes express aldosterone synthase (CYP11B2) and produce aldo. The mineralocorticoid receptor (MR), which is responsible for aldo signaling, is also found in these cells, but its role in regulating adipose tissue interactions with the vasculature is unknown. In this study, we investigated mechanisms whether MR activation in adipocytes regulates vascular reactivity. Conditional transgenic mice that overexpress MR in an adipocyte-specific manner were studied. Vascular reactivity of resistance mesenteric arteries to acetylcholine (Ach), sodium nitroprusside and phenylephrine (Phe), in the absence or presence of fat conditioned medium (Fcm) from control and adipocyte overexpressing MR (MROE) mice, was performed by myography. In basal conditions, endothelial dysfunction was not observed in MROE or control (Ctr) mice. However, exposure of arteries from control mice to Fcm from MROE mice induces endothelial dysfunction (Ach 10 -6 M: 77.5±9.6% no Fcm vs. 49.8±7.5% Fcm, p<0.05), an effect blocked by N-acetyl-cysteine (an antioxidant) (Ach 10 -6 M: 82.2±6.6%). Resistance arteries from MROE mice had decreased Phe-induced contraction, compared to control mice (Phe 10 -5 M: 2.7±0.2 mN/mm Ctr vs. 1.7±0.2 mN/mm MROE, p<0.05). Rho Kinase activity, which regulates vascular contraction, is decreased in arteries and adipo tissue from MROE (mesenteric arteries, Ctr: 100±16.2% vs. MROE: 31.1±6.1%, arbitrary units, p<0.01; adipose tissue, Ctr: 100±12.6% vs. MROE: 51.3±9.3%, arbitrary units, p<0.01). In conclusion, MR in adipocytes may play an important role in the regulation of vascular function, through redox-sensitive pathways and activation of Rho kinase. Our study identifies novel mechanisms linking vascular/adipose tissue biology and aldo/MR activation, which may be particularly important in vascular dysfunction associated with hypertension and hyperaldosteronism.

scholarly journals The atypical structure and function of newborn arterial endothelium is mediated by Rho/Rho kinase signaling

2014 ◽  
Vol 307 (4) ◽  
pp. H628-H632 ◽  
Author(s):  
Sheila Flavahan ◽  
Nicholas A. Flavahan
Keyword(s):  
Laser Scanning ◽  
Rho Kinase ◽  
Laser Scanning Microscopy ◽  
Scanning Microscopy ◽  
Stress Fibers ◽  
Light Chains ◽  
Myosin Light Chains ◽  
Kinase Signaling ◽  
No Donor ◽  
Kinase Inhibition

Endothelium of fetal or newborn arteries is atypical, displaying actin stress fibers and reduced nitric oxide (NO)-mediated dilatation. This study tested the hypothesis that Rho/Rho kinase signaling, which promotes endothelial stress fibers and inhibits endothelial dilatation, contributed to this phenotype. Carotid arteries were isolated from newborn [ postnatal day 1 (P1)], P7, and P21 mice. Endothelial dilatation to acetylcholine (pressure myograph) was minimal at P1, increased at P7, and further increased at P21. Inhibition of Rho (C3 transferase) or Rho kinase (Y27632, fasudil) significantly increased dilatation to acetylcholine in P1 arteries but had no effect in P7 or P21 arteries. After inhibition of NO synthase ( NG-nitro-l-arginine methyl ester), Rho kinase inhibition no longer increased acetylcholine responses in P1 arteries. Rho kinase inhibition did not affect dilatation to the NO donor DEA-NONOate. The endothelial actin cytoskeleton was labeled with phalloidin and visualized by laser-scanning microscopy. In P1 arteries, the endothelium had prominent transcytoplasmic stress fibers, whereas in P7 and P21 arteries, the actin fibers had a significantly reduced intensity and were restricted to cell borders. Phosphorylation of myosin light chains, a Rho kinase substrate, was highest in P1 endothelium and significantly reduced in P7 and P21 endothelium (laser-scanning microscopy). In P1 arteries, inhibition of Rho (C3 transferase) or Rho kinase (Y27632) significantly reduced the intensity of actin fibers, which were restricted to cell borders. Similarly, in P1 arteries, Rho inhibition significantly reduced endothelial levels of phosphorylated myosin light chains. These results indicate that the atypical function and morphology of newborn endothelium is mediated by Rho/Rho kinase signaling.

Endokrinológiai tényezők és metabolikus folyamatok szerepe az élettartam szabályozásában

2021 ◽  
Vol 162 (33) ◽  
pp. 1318-1327
Author(s):  
Tamás Halmos ◽  
Ilona Suba
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Life Expectancy ◽  
Significant Risk ◽  
Low Grade ◽  
Aging Effects ◽  
Protective Function ◽  
Beneficial Effects ◽  
Age Related

Összefoglaló. Az emberek a lehető leghosszabb ideig akarnak élni, jó egészségben. Ha kiküszöbölnénk a kedvezőtlen külső körülményeket, a várható élettartam meghaladhatná a 100 évet. A 20. és 21. században a jóléti társadalmakban a várható élettartam jelentősen megnőtt, így Magyarországon is. Az áttekintett irodalom alapján megvizsgáltuk, hogy a genetika és az öröklődés mellett milyen endokrinológiai és metabolikus tényezők játszanak szerepet az élet meghosszabbításában. Megvizsgáltunk minden endogén tényezőt, amely pozitívan vagy negatívan befolyásolhatja az életkorral összefüggő betegségeket (Alzheimer-kór, szív- és érrendszeri betegségek, rák) és az élettartamot. Kiemeltük a hyperinsulinaemia, az inzulinrezisztencia, a metabolikus szindróma öregedést gyorsító hatását, az inzulinszerű növekedési hormon-1 ellentmondásos szerepét, valamint az élet meghosszabbításában részt vevő, újabban felfedezett peptideket, mint a klotho és a humanin. Ismertettük a mitochondriumok szerepét az élettartam meghatározásában, bemutattuk a mitohormesis folyamatát és annak stresszvédő funkcióját. Bemutattuk a rapamicin célszervét, az mTOR-t, amelynek gátlása meghosszabbítja az élettartamot, valamint a szirtuinokat. Kitértünk az autophagia folyamatára, és ismertettük a szenolitikumok szerepét az öregedésben. Az időskori autoimmunitás csökkenése hozzájárul az élettartam rövidüléséhez, utaltunk a thymus koordináló szerepére. Kiemeltük a bélmikrobiom fontos szerepét az élettartam szabályozásában. Hivatkoztunk a „centenáriusok” megfigyeléséből nyert humánadatokra. Megvizsgáltuk, milyen beavatkozási lehetőségek állnak rendelkezésre az egészségben tölthető élettartam meghosszabbításához. Az életmódbeli lehetőségek közül kiemeltük a kalóriabevitel-csökkentés és a testmozgás jótékony szerepét. Megvizsgáltuk egyes gyógyszerek feltételezett hatásait. Ezek közé tartozik a metformin, az akarbóz, a rezveratrol. E gyógyszerek mindegyikének hatása hasonló a kalóriamegszorításéhoz. Nincs olyan „csodaszer”, amely igazoltan meghosszabbítja az élettartamot emberben. Egyes géneknek és génmutációknak jótékony hatásuk van, de ezt környezeti tényezők, betegségek, balesetek és más külső ártalmak módosíthatják. Kiemeljük az elhízás, az alacsony fokozatú gyulladás és az inzulinrezisztencia öregedésre gyakorolt gyorsító hatását. A metabolikus szindróma elterjedtsége miatt ez jelentős népegészségügyi kockázatot jelent. Az inzulin, a növekedési hormon és az inzulinszerű növekedési faktorok hatásainak értékelése továbbra is ellentmondásos. Az egészséges, szellemileg és fizikailag aktív életmód, a kalóriacsökkentés mindenképpen előnyös. Az életet meghosszabbító szerek értékelése még vitatott. Orv Hetil. 2021; 162(33): 1318–1327. Summary. People want to live as long as possible in good health. If we eliminate the unfavorable external conditions, the life expectancy could exceed 100 years. In the 20th and 21th centuries, life expectancy in welfare societies increased significantly, including in Hungary. Based on the reviewed literature, we examined what endocrinological and metabolic factors play a role in prolonging life in addition to genetics and inheritance. We examined all endogenous factors that can positively or negatively affect age-related diseases (Alzheimer’s disease, cardiovascular disease, cancer) and longevity. We highlighted the aging effects of hyperinsulinemia, insulin resistance, metabolic syndrome, the controversial role of insulin-like growth factor-1, and more recently discovered peptides involved in prolonging lifespan, such as klotho and humanin. We described the role of mitochondria in determining longevity, we demonstrated the process of mitohormesis and its stress-protective function. We presented the target organ of rapamycin, mTOR, the inhibition of which prolongs lifespan, as well as sirtuins. We covered the process of autophagy and described the role of senolytics in aging. The decrease in autoimmunity in old age contributes to the shortening of life expectancy, we referred to the coordinating role of the thymus. We highlighted the important role of intestinal microbiome in the regulation of longevity. We referred to human data obtained from observations on “centenarians”. We examined what intervention options are available to prolong healthy life expectancy. Among the lifestyle options, we highlighted the beneficial role of calorie reduction and exercise. We examined the putative beneficial effects of some drugs. These include metformin, acarbose, resveratrol. The effect of each of these drugs is similar to calorie restriction. There is no “miracle cure” that has been shown to prolong life-span in humans. Some genes and gene mutations have beneficial effects, but this can be modified by environmental factors, diseases, accidents, and other external harms. We highlight the accelerating effects of obesity, low-grade inflammation, and insulin resistance on aging. Due to the prevalence of metabolic syndrome, this poses a significant risk to public health. The assessment of the effects of insulin, growth hormone, and insulin-like growth factors remains controversial. A healthy, mentally and physically active lifestyle, calorie reduction is definitely beneficial. The evaluation of life-prolonging agents is still controversial. Orv Hetil. 2021; 162(33): 1318–1327.

Abstract 461: Role of Physical Training Intensity in Metabolic and Cardiovascular Dysfunctions in a Fructose Overload Model

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Jacqueline F Machi ◽  
Nathalia Bernardes ◽  
Danielle S Dias ◽  
Cristiano Mostarda ◽  
Edson Moreira ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Maximum Speed ◽  
Normal Range ◽  
Maximal Exercise Test ◽  
Baroreceptor Sensitivity ◽  
Chronic Effects ◽  
Male Wistar Rats

This study evaluated the chronic effects of the run and walk in the metabolic and cardiovascular parameters of a metabolic syndrome experimental model. Male Wistar rats were divided into 4 groups(n=8): Control (C),Sedentary Fructose (SF), Fructose Run (FR) and Fructose Walk (FW, n= 8). Metabolic syndrome (MS) induction was performed with D-fructose in drinking water for 18 weeks. The exercise training was initiated after the nineth week of treatment with fructose and was held for 8 weeks (60 minutes/day, 5 times / week). The FW and FR were performed on a treadmill (1 h/day; 5 days/wk for 8 wk), with ∼20% and 60% intensities respectively of the maximum speed in a maximal exercise test. Plasma glucose, triglycerides, insulin resistance, adipose tissue, blood pressure, heart rate, baroreceptor sensitivity and sympathetic and parasympathetic tone, were evaluated at the end of protocol. The results showed that run and walking decreased the adipose tissue (FR: 2.97±0.2; FW: 4.26±0.9; SF: 6.49±0.6; C: 3.23±0.2 g). The glycemia values remained within the normal range,(FR: 86.7±2.3; WF: 91.0±1.4; SF: 70.2±1.9; C: 84±2.3 mg/dl), however only the FR group decreased the triglycerides levels (FR: 133±8.8; FW: 159±10.2; SF: 220±6.3; C: 96± 4.2 mg/dl), and the insulin resistance (FR: 4.37±0.1; FW: 3.55±0.2; SF: 2.79±0.3; C: 4.86±0.3 %/min). The FR group showed a reduction in mean arterial pressure (FR: 111±4.5, FW: 125±4.1; SF: 137±2.6, C: 113±1.5 mmHg) and increased of bradycardic (FR 1.76±0.08; FW 1.31±0.10; SF 1.37±0.10; C 1.72±0.14 bpm/mmHg) and tachycardic response to BP changes (FR 4.02±0.32; FW 2.56±0.16; SF 1.97±0.15; C (and C 3.25±0.37 bpm/mmHg). Finally we observed that only the FR group showed an increase of the vagal tone (FR: 72.3±8.1, FW: 47.3±6.7; FS: 40.3±4.6, C: 60.7±6.5 bpm). In conclusion, our results suggest that training walk (FW), a practice widely recommended, is especially effective for the treatment of metabolic disorders, whereas controlled exercise (FR) seems to encompass hemodynamic and metabolic aspects. This application is easy and within reach of the majority of the population, indicating that this practice should be encouraged and may be effective in managing cardiovascular risk in MS as start therapeutic. Sources of Funding:FAPESP.

Role of endothelium-derived relaxing factors in the renal response to vasoactive agents in hypothyroid rats

2003 ◽  
Vol 285 (1) ◽  
pp. E182-E188 ◽  
Author(s):  
Juan Manuel Moreno ◽  
Rosemary Wangensteen ◽  
Juan Sainz ◽  
Isabel Rodríguez-Gomez ◽  
Virginia Chamorro ◽  
...  
Keyword(s):  
Vascular Reactivity ◽  
Ang Ii ◽  
Vasoactive Agents ◽  
Normal Response ◽  
No Donor ◽  
Increased Sensitivity ◽  
Renal Vascular ◽  
And Control ◽  
Renal Responses

This study analyzed the role of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in the abnormal renal vascular reactivity of hypothyroid rats. Renal responses to vasoconstrictors [VC: phenylephrine (PHE) and ANG II] and vasodilators [VD: ACh, sodium nitroprusside (SNP), and papaverine (PV)] were studied in kidneys from control and hypothyroid rats under normal conditions and after NO or EDHF blockade. NO was blocked by the administration of Nω-nitro-l-arginine methyl ester (l-NAME) and EDHF by the administration of tetraethylammonium (TEA) or by an increased extracellular K+. The response to VC was also evaluated after endothelium removal. Hypothyroid kidneys showed reduced responsiveness to PHE and a normal response to ANG II. l-NAME and TEA administration produced an increased sensitivity to PHE and to ANG II in control preparations. l-NAME also increased the response to PHE in hypothyroid kidneys, but the differences between control and hypothyroid kidneys were maintained. TEA administration did not change the response to either VC in hypothyroid preparations. In endothelium-removed preparations, TEA was unable to increase pressor responsiveness to VC. Hypothyroid kidneys showed reduced responsiveness to ACh and SNP and normal response to PV. The differences between hypothyroid and control preparations in the responses to ACh and SNP were maintained after l-NAME or increased K+. In conclusion, this study shows that 1) the attenuated response to PHE in hypothyroidism is not related to an increased production of endothelium-derived relaxing factors NO and EDHF; 2) the response to VC in hypothyroid preparations is insensitive to EDHF blockade; and 3) hypothyroid preparations have a reduced reactivity to the NO donor, and NO-independent vasodilatation remains unaffected.

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