Exercise changes regional vascular control by commissural NTS in spontaneously hypertensive rats

Ogihara CA, Schoorlemmer GHM, Levada AC, Pithon-Curi TC, Curi R, Lopes OU, Colombari E, Sato MA. Exercise changes regional vascular control by commissural NTS in spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol 299: R291-R297, 2010. First published April 21, 2010; doi: 10.1152/ajpregu.00055.2009.-Inhibition of the commissural nucleus of the solitary tract (commNTS) induces a fall in sympathetic nerve activity and blood pressure in spontaneously hypertensive rats (SHR), which suggests that this subnucleus of the NTS is a source of sympathoexcitation. Exercise training reduces sympathetic activity and arterial pressure. The purpose of the present study was to investigate whether the swimming exercise can modify the regional vascular responses evoked by inhibition of the commNTS neurons in SHR and normotensive Wistar-Kyoto (WKY) rats. Exercise consisted of swimming, 1 h/day, 5 days/wk for 6 wks, with a load of 2% of the body weight. The day after the last exercise session, the rats were anesthetized with intravenous alpha-chloralose, tracheostomized, and artificially ventilated. The femoral artery was cannulated for mean arterial pressure (MAP) and heart rate recordings, and Doppler flow probes were placed around the lower abdominal aorta and superior mesenteric artery. Microinjection of 50 mM GABA into the commNTS caused similar reductions in MAP in swimming and sedentary SHR (-25 +/- 6 and -30 +/- 5 mmHg, respectively), but hindlimb vascular conductance increased twofold in exercised vs. sedentary SHR (54 +/- 8 vs. 24 +/- 5%). GABA into the commNTS caused smaller reductions in MAP in swimming and sedentary WKY rats (-20 +/- 4 and -16 +/- 2 mmHg). Hindlimb conductance increased fourfold in exercised vs. sedentary WKY rats (75 +/- 2% vs. 19 +/- 3%). Therefore, our data suggest that the swimming exercise induced changes in commNTS neurons, as shown by a greater enhancement of hindlimb vasodilatation in WKY vs. SHR rats in response to GABAergic inhibition of these neurons.

Augmented muscle vasodilatory responses in obese children with Glu27 beta(2)-adrenoceptor polymorphism

This study examined forearm vasodilatation during mental challenge and exercise in 72 obese children (OC; age = 10 +/- 0.1 years) homozygous with polymorphism in the allele 27 of the beta(2)-adrenoceptors: Gln27 (n = 61) and Glu27 (n = 11). Forearm blood flow was recorded during 3 min of each using the Stroop color-word test (MS) and handgrip isometric exercise. Baseline hemodynamic and vascular measurements were similar. During the MS, peak forearm vascular conductance was significantly greater in group Glu27 (Delta = 0.35 +/- 0.4 vs. 0.12 +/- 0.1 units, respectively, p = .042). Similar results were found during exercise (Delta = 0.64 +/- 0.1 vs. 0.13 +/- 0.1 units, respectively, p = .035). Glu27 OC increased muscle vasodilatory responsiveness upon the MS and exercise.

Exercise training improves muscle vasodilatation in individuals with T786C polymorphism of endothelial nitric oxide synthase gene

Negrão M.V, Alves CR, Alves G.B, Pereira A.C, Dias R.G, Laterza M.C, Mota G.F, Oliveira E.M, Bassaneze V, Krieger J.E, Negrão C.E, Rondon M.U.P. Exercise training improves muscle vasodilatation in individuals with T786C polymorphism of endothelial nitric oxide synthase gene. Physiol Genomics 42A: 71-77, 2010. First published July 6, 2010; doi:10.1152/physiolgenomics.00145.2009.-Allele T at promoter region of the eNOS gene has been associated with an increase in coronary disease mortality, suggesting that this allele increases susceptibility for endothelial dysfunction. In contrast, exercise training improves endothelial function. Thus, we hypothesized that: 1) Muscle vasodilatation during exercise is attenuated in individuals homozygous for allele T, and 2) Exercise training improves muscle vasodilatation in response to exercise for TT genotype individuals. From 133 preselected healthy individuals genotyped for the T786C polymorphism, 72 participated in the study: TT (n = 37; age 27 +/- 1 yr) and CT + CC (n = 35; age 26 +/- 1 yr). Forearm blood flow (venous occlusion plethysmography) and blood pressure (oscillometric automatic cuff) were evaluated at rest and during 30% handgrip exercise. Exercise training consisted of three sessions per week for 18 wk, with intensity between anaerobic threshold and respiratory compensation point. Resting forearm vascular conductance (FVC, P = 0.17) and mean blood pressure (P = 0.70) were similar between groups. However, FVC responses during handgrip exercise were significantly lower in TT individuals compared with CT + CC individuals (0.39 +/- 0.12 vs. 1.08 +/- 0.27 units, P = 0.01). Exercise training significantly increased peak VO(2) in both groups, but resting FVC remained unchanged. This intervention significantly increased FVC response to handgrip exercise in TT individuals (P = 0.03), but not in CT + CC individuals (P = 0.49), leading to an equivalent FVC response between TT and CT + CC individuals (1.05 +/- 0.18 vs. 1.59 +/- 0.27 units, P = 0.27). In conclusion, exercise training improves muscle vasodilatation in response to exercise in TT genotype individuals, demonstrating that genetic variants influence the effects of interventions such as exercise training.

Abnormal Neurovascular Control in Anabolic Androgenic Steroids Users

NUNES ALVES, M. J. N., M. R. DOS SANTOS, R. G. DIAS, C. A. AKIHO, M. C. LATERZA, M. U. P. B. RONDON, R. L. DE MORAES MOREAU, and C. E. NEGRAO. Abnormal Neurovascular Control in Anabolic Androgenic Steroids Users. Med. Sci. Sports Exerc., Vol. 42, No. 5, pp. 865-871, 2010. Purpose: Previous studies showed that anabolic androgenic steroids (AAS) increase vascular resistance and blood pressure (BP) in humans. In this study, we tested the hypotheses 1) that AAS users would have increased muscle sympathetic nerve activity (MSNA) and reduced forearm blood flow (FBF) compared with AAS nonusers and 2) that there would be an association between MSNA and 24-h BP. Methods: Twelve AAS users aged 31 +/- 2 yr (means +/- SE) and nine age-matched AAS nonusers aged 29 T 2 yr participated in the study. All individuals were involved in strength training for at least 2 yr. AAS was determined by urine test (chromatography-mass spectrometry). MSNA was directly measured by microneurography technique. FBF was measured by venous occlusion plethysmography. BP monitoring consisted of measures of BP for 24 h. Results: MSNA was significantly higher in AAS users than that in AAS nonusers (29 +/- 3 vs 20 +/- 1 bursts per minute, P = 0.01). FBF (1.92 +/- 0.17 vs 2.77 +/- 0.24 mL.min(-1).100 mL(-1), P = 0.01) and forearm vascular conductance (2.01 +/- 0.17 vs 2.86 +/- 0.31 U, P = 0.02) were significantly lower in AAS users than that in AAS nonusers. Systolic (131 +/- 4 vs 120 +/- 3 mm Hg, P = 0.001), diastolic (74 +/- 4 vs 68 +/- 3 mm Hg, P = 0.02), and mean BP (93 +/- 4 vs 86 +/- 3 mm Hg, P = 0.005) and heart rate (74 +/- 3 vs 68 +/- 3 bpm, P = 0.02) were significantly higher in AAS users when compared with AAS nonusers. Further analysis showed that there was a significant correlation between MSNA and 24-h mean BP (r = 0.75, P = 0.002). Conclusions: AAS increases MSNA and reduces muscle blood flow in young individuals. In addition, the increase in BP levels in AAS users is associated with augmented sympathetic outflow. These findings suggest that AAS increases the susceptibility for cardiovascular disease in humans.

A high-fat meal impairs muscle vasodilatation response to mental stress in humans with Glu27 beta(2)-adrenoceptor polymorphism

Background: Forearm blood flow responses during mental stress are greater in individuals homozygous for the Glu27 allele. A high-fat meal is associated with impaired endothelium-dependent dilatation. We investigated the impact of high-fat ingestion on the muscle vasodilatory responses during mental stress in individuals with the Glu27 allele and those with the Gln27 allele of the beta(2)-adrenoceptor gene. Methods: A total of 162 preselected individuals were genotyped for the Glu27Gln beta(2)-adrenoceptor polymorphism. Twenty-four individuals participated in the study. Fourteen were homozygous for the Gln27 allele (Gln27Gln, 40 +/- 2 years; 64 +/- 2 kg), and 10 were homozygous for the Glu27 allele (Glu27Glu, 40 +/- 3 years; 65 +/- 3 kg). Forearm blood flow was evaluated by venous occlusion plethysmography before and after ingestion of 62 g of fat. Results: The high-fat meal caused no changes in baseline forearm vascular conductance (FVC, 2.2 +/- 0.1 vs. 2.4 +/- 0.2; P = 0.27, respectively), but reduced FVC responses to mental stress (1.5 +/- 0.2 vs. 0.8 +/- 0.2 units; P = 0.04). When volunteers were divided according to their genotypes, baseline FVC was not different between groups (Glu27Glu = 2.4 +/- 0.1 vs. Gln27Gln = 2.1 +/- 0.1 units; P = 0.08), but it was significantly greater in Glu27Glu individuals during mental stress (1.9 +/- 0.4 vs. 1.0 +/- 0.3 units; P = 0.04). High-fat intake eliminated the difference in FVC responses between Glu27Glu and Gln27Gln individuals (FVC, 1.3 +/- 0.4 vs. 1.2 +/- 0.4; P = 0.66, respectively). Conclusion: These findings demonstrate that a high-fat meal impairs muscle vasodilatation responses to mental stress in humans. However, this reduction can be attributed to the presence of the homozygous Glu27 allele of the beta(2)-adrenoceptor gene.

Glu298Asp eNOS gene polymorphism causes attenuation in nonexercising muscle vasodilatation

Dias RG, Alves MJ, Pereira AC, Rondon MU, dos Santos MR, Krieger JE, Krieger MH, Negrao CE. Glu298Asp eNOS gene polymorphism causes attenuation in nonexercising muscle vasodilatation. Physiol Genomics 37: 99-107, 2009. First published January 21, 2009; doi:10.1152/physiolgenomics.90368.2008.-The influence of Glu298Asp endothelial nitric oxide synthase (eNOS) polymorphism in exercise-induced reflex muscle vasodilatation is unknown. We hypothesized that nonexercising forearm blood flow (FBF) responses during handgrip isometric exercise would be attenuated in individuals carrying the Asp298 allele. In addition, these responses would be mediated by reduced eNOS function and NO-mediated vasodilatation or sympathetic vasoconstriction. From 287 volunteers previously genotyped, we selected 33 healthy individuals to represent three genotypes: Glu/Glu [n = 15, age 43 +/- 3 yr, body mass index (BMI) 22.9 +/- 0.3 kg/m(2)], Glu/Asp (n = 9, age 41 +/- 3 yr, BMI 23.7 +/- 1.0 kg/m(2)), and Asp/Asp (n = 9, age 40 +/- 4 yr, BMI 23.5 +/- 0.9 kg/m(2)). Heart rate (HR), mean blood pressure (MBP), and FBF (plethysmography) were recorded for 3 min at baseline and 3 min during isometric handgrip exercise. Baseline HR, MBP, FBF, and forearm vascular conductance (FVC) were similar among genotypes. FVC responses to exercise were significantly lower in Asp/Asp when compared with Glu/Asp and Glu/Glu (Delta = 0.07 +/- 0.14 vs. 0.64 +/- 0.20 and 0.57 +/- 0.09 units, respectively; P = 0.002). Further studies showed that intra-arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA) did not change FVC responses to exercise in Asp/Asp, but significantly reduced FVC in Glu/Glu (Delta = 0.79 +/- 0.14 vs. 0.14 +/- 0.09 units). Thus the differences between Glu/Glu and Asp/Asp were no longer observed (P = 0.62). L-NMMA + phentolamine increased similarly FVC responses to exercise in Glu/Glu and Asp/Asp (P = 0.43). MBP and muscle sympathetic nerve activity increased significant and similarly throughout experimental protocols in Glu/Glu and Asp/Asp. Individuals who are homozygous for the Asp298 allele of the eNOS enzyme have attenuated nonexercising muscle vasodilatation in response to exercise. This genotype difference is due to reduced eNOS function and NO-mediated vasodilatation, but not sympathetic vasoconstriction.

Effects of sinoaortic Denervation on Hemodynamic parameters during natural sleep in rats

Study Objectives: To analyze the role of arterial baroreflex on hemodynamic changes during synchronized and desynchronized sleep phases of natural sleep in rats. Design: Experimental study. Setting: Laboratory. Participants: Seventeen male Wistar rats. Interventions: No intervention (control, n = 8) or sinoaortic denervation (SAD, n = 9). Measurements and Results: Sleep phases were monitored by electrocorticogram, and blood pressure was measured directly by a catheter in the carotid artery. Cardiac output, as well as total and regional vascular resistances, were determined by measuring the subdiaphragmatic aorta and iliac artery flows with Doppler flow probes, respectively. In contrast to the control group, the SAD group had a strong reduction in blood pressure (-19.9% +/- 2.6% vs -0.7% +/- 2.1%) during desynchronized sleep, and cardiac output showed an exacerbated reduction (-10.4% +/- 3.5% vs 1.1% +/- 1.7%). In SAD rats, total vascular resistance decreased during desynchronized sleep (-10.1% +/- 3.5% vs -1.0% +/- 1.7%), and the increase in regional vascular resistance observed in the control group was abolished (27.5% +/- 8.3% vs -0.8% +/- 9.4%). Conclusions: SAD caused profound changes in blood pressure, cardiac output, and total vascular resistance, with a significant increase in muscle vascular resistance during synchronized sleep. Our results suggest that baroreflex plays an important role in maintaining the normal balance of cardiac output and total vascular resistance during sleep.

Multiphase flow in the vascular system of wood: From microscopic exploration to 3-D Lattice Boltzmann experiments

This paper provides insights into liquid free water dynamics in wood vessels based on Lattice Boltzmann experiments. The anatomy of real wood samples was reconstructed from systematic 3-D analyses of the vessel contours derived from successive microscopic images. This virtual vascular system was then used to supply fluid-solid boundary conditions to a two-phase Lattice Boltzmann scheme and investigate capillary invasion of this hydrophilic porous medium. Behavior of the liquid phase was strongly dependent on anatomical features, especially vessel bifurcations and reconnections. Various parameters were examined in numerical experiments with ideal vessel bifurcations, to clarify our interpretation of these features. (c) 2010 Elsevier Ltd. All rights reserved.

Regional Blood Flow Distribution and Oxygen Metabolism During Mesenteric Ischemia and Congestion

Background. Acute mesenteric ischemia is a potentially fatal vascular emergency with mortality rates ranging between 60% and 80%. Several studies have extensively examined the hemodynamic and metabolic effects of superior mesenteric artery occlusion. On the other hand, the cardiocirculatory derangement and the tissue damage induced by intestinal outflow obstruction have not been investigated systematically. For these reasons we decided to assess the initial impact of venous mesenteric occlusion on intestinal blood flow distribution, and correlate these findings with other systemic and regional perfusion markers. Methods. Fourteen mongrel dogs were subjected to 45 min of superior mesenteric artery (SMAO) or vein occlusion (SMVO), and observed for 120 min after reperfusion. Systemic hemodynamics were evaluated using Swan-Ganz and arterial catheters. Regional blood flow (ultrasonic flow probes), intestinal O(2)-derived variables, and mesenteric-arterial and tonometric-arterial pCO(2) gradients (D(mv-a)pCO(2) and D(t-a)pCO(2)) were also calculated. Results. SMVO was associated with hypotension and low cardiac output. A significant increase in the regional pCO(2) gradients was also observed in both groups during the ischemic period. After reperfusion, a progressive reduction in D(mv-a)pCO(2) occurred in the SMVO group; however, no improvement in D(t-p)CO(2) was observed. The histopathologic injury scores were 2.7 +/- 0.5 and 4.8 +/- 0.2 for SMAO and SMVO, respectively. Conclusions. SMV occlusion promoted early and significant hemodynamic and metabolic derangement at systemic and regional levels. Additionally, systemic pCO(2) gradient is not a reliable parameter to evaluate the local intestinal oxygenation. Finally, the D(t-a)pCO(2) correlates with histologic changes during intestinal congestion or ischemia. However, minor histologic changes cannot be detected using this methodology. (C) 2010 Elsevier Inc. All rights reserved.

Vascular diseases and old age mental disorders: an update of neuroimaging findings

Purpose of review To review neuroimaging findings that have been reported in samples of patients with cardiovascular disorders and their association with the onset of Alzheimer`s disease, vascular dementia, depression and bipolar disorder in the elderly and to highlight the implications of these findings to the knowledge about the pathophysiology of psychiatric disorders in old age, as well as their potential clinical implications. Recent findings Vascular risk factors, such as hypertension, diabetes, dyslipidemia, smoking habits and heart failure, have all been associated with signs of cerebrovascular dysfunction, including structural MRI findings of signal hyperintensities, lacunes and stroke and functional imaging findings of brain regional hypoperfusion and hypometabolism. Such brain abnormalities have been found to increase the risk of onset of psychiatric disorder (depression, bipolar and dementia) in old age. Summary As vascular risk factors are potentially modifiable when detected in midlife, the early characterization of brain changes associated with the presence of cardiovascular diseases holds promise to afford clinical applications in psychiatry, providing new perspectives for the prevention of old age psychiatric disorders.

Short-Term Effects of Hydroxyethylstarch Resuscitation on Systemic and Regional Hemodynamics and Metabolism in a Brain-Dead Canine Model

Background. Hydroxyethylstarch (HES) is a synthetic polymer of glucose that has been suggested for therapeutic use in long-term plasma expansion. The aim of this study was to test the hypothesis that the infusion of a small volume of HES may provide benefits in systemic and regional hemodynamics and metabolism in a brain-dead canine model compared with large volume crystalloid resuscitation. Methods. Fourteen mongrel dogs were subjected to a brain-death protocol by consecutive insufflations of a balloon catheter in the epidural space. One hour after induction of brain-death, the animals were randomly assigned to two groups: NS (0.9% NaCl, 33mL/kg), and HES (6% HES 450/0.7, 17mL/Kg). Systemic and regional hemodynamics were evaluated using Swan-Ganz, ultrasonic flowprobes, and arterial catheters. Serial blood samples were collected for blood gas, electrolyte, and serum chemistry analysis. Systemic, hepatic, and splanchnic O(2)-derived variables were also calculated. Results. Epidural balloon insufflations induced a significant increase in mean arterial pressure, cardiac output (MAP and CO, respectively), regional blood flow, and systemic vascular resistance. Following the hyperdynamic phase, severe hypotension with normalization of systemic and regional blood flow was observed. Fluid resuscitation induced a prompt increase in MAP, CO, and portal vein blood flow, and a significant reduction in systemic and pulmonary vascular resistance. There were no differences between groups in metabolic indices, liver function tests (LFTs), or renal function tests. HES was more effective than NS in restoring cardiac performance in the first 2h after fluid resuscitation (P < 0.05). Both tested solutions partially and temporarily restored systemic and regional oxygen delivery. Conclusion. Small volumes of 6% HES 450/0.7 improved cardiovascular performance and provided the same regional hemodynamic and metabolic benefits of large volumes of isotonic crystalloid solutions. (C) 2011 Elsevier Inc. All rights reserved.

Endothelial dysfunction in cardiovascular and endocrine-metabolic diseases: an update

The endothelium plays a vital role in maintaining circulatory homeostasis by the release of relaxing and contracting factors. Any change in this balance may result in a process known as endothelial dysfunction that leads to impaired control of vascular tone and contributes to the pathogenesis of some cardiovascular and endocrine/metabolic diseases. Reduced endothelium-derived nitric oxide (NO) bioavailability and increased production of thromboxane A2, prostaglandin H2 and superoxide anion in conductance and resistance arteries are commonly associated with endothelial dysfunction in hypertensive, diabetic and obese animals, resulting in reduced endothelium-dependent vasodilatation and in increased vasoconstrictor responses. In addition, recent studies have demonstrated the role of enhanced overactivation ofβ-adrenergic receptors inducing vascular cytokine production and endothelial NO synthase (eNOS) uncoupling that seem to be the mechanisms underlying endothelial dysfunction in hypertension, heart failure and in endocrine-metabolic disorders. However, some adaptive mechanisms can occur in the initial stages of hypertension, such as increased NO production by eNOS. The present review focuses on the role of NO bioavailability, eNOS uncoupling, cyclooxygenase-derived products and pro-inflammatory factors on the endothelial dysfunction that occurs in hypertension, sympathetic hyperactivity, diabetes mellitus, and obesity. These are cardiovascular and endocrine-metabolic diseases of high incidence and mortality around the world, especially in developing countries and endothelial dysfunction contributes to triggering, maintenance and worsening of these pathological situations.

Effect of gender on training-induced vascular remodeling in SHR

There is accumulating evidence that physical inactivity, associated with the modern sedentary lifestyle, is a major determinant of hypertension. It represents the most important modifiable risk factor for cardiovascular diseases, which are the leading cause of morbidity and mortality for both men and women. In addition to involving sympathetic overactivity that alters hemodynamic parameters, hypertension is accompanied by several abnormalities in the skeletal muscle circulation including vessel rarefaction and increased arteriole wall-to-lumen ratio, which contribute to increased total peripheral resistance. Low-intensity aerobic training is a promising tool for the prevention, treatment and control of high blood pressure, but its efficacy may differ between men and women and between male and female animals. This review focuses on peripheral training-induced adaptations that contribute to a blood pressure-lowering effect, with special attention to differential responses in male and female spontaneously hypertensive rats (SHR). Heart, diaphragm and skeletal muscle arterioles (but not kidney arterioles) undergo eutrophic outward remodeling in trained male SHR, which contributed to a reduction of peripheral resistance and to a pressure fall. In contrast, trained female SHR showed no change in arteriole wall-to-lumen ratio and no pressure fall. On the other hand, training-induced adaptive changes in capillaries and venules (increased density) were similar in male and female SHR, supporting a similar hyperemic response to exercise.

Structural properties of lipid reconstructs and lipid composition of normotensive and hypertensive rat vascular smooth muscle cell membranes

Multiple cell membrane alterations have been reported to be the cause of various forms of hypertension. The present study focuses on the lipid portion of the membranes, characterizing the microviscosity of membranes reconstituted with lipids extracted from the aorta and mesenteric arteries of spontaneously hypertensive (SHR) and normotensive control rat strains (WKY and NWR). Membrane-incorporated phospholipid spin labels were used to monitor the bilayer structure at different depths. The packing of lipids extracted from both aorta and mesenteric arteries of normotensive and hypertensive rats was similar. Lipid extract analysis showed similar phospholipid composition for all membranes. However, cholesterol content was lower in SHR arteries than in normotensive animal arteries. These findings contrast with the fact that the SHR aorta is hyporeactive while the SHR mesenteric artery is hyperreactive to vasopressor agents when compared to the vessels of normotensive animal strains. Hence, factors other than microviscosity of bulk lipids contribute to the vascular smooth muscle reactivity and hypertension of SHR. The excess cholesterol in the arteries of normotensive animal strains apparently is not dissolved in bulk lipids and is not directly related to vascular reactivity since it is present in both the aorta and mesenteric arteries. The lower cholesterol concentrations in SHR arteries may in fact result from metabolic differences due to the hypertensive state or to genes that co-segregate with those that determine hypertension during the process of strain selection.

Cuidador familiar de seqüelados de acidente vascular cerebral: significado e implicações

O acidente vascular cerebral (AVC) está entre as principais causas de morte no mundo. Diante das incapacidades impostas pelo AVC, surge o cuidador familiar. O objetivo desta pesquisa foi analisar o significado e as implicações de se tornar cuidador de um indivíduo seqüelado de AVC. Trata-se de um estudo qualitativo, realizado com cinco cuidadores, em Londrina-PR, no período de agosto a dezembro de 2005. Os dados foram coletados por meio de entrevistas semi-estruturadas e submetidos à análise de discurso proposta por Martins e Bicudo. Da análise das entrevistas emergiram sete categorias: voltando-se para o Ser cuidado, descrevendo os cuidados, apresentando as mudanças, o apoio da espiritualidade, compreendendo o significado do cuidado, expressando as necessidades para cuidar e perspectivas para o futuro. Os resultados revelaram que ser cuidador familiar é um fenômeno complexo, que gera nos sujeitos sentimentos de alegria e felicidade concomitantes aos sentimentos de medo, ansiedade e revolta.