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1.
Physiol Rep ; 7(15): e14168, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31368238

RESUMO

Endothelium derived signaling mechanisms play an important role in regulating vascular tone and endothelial dysfunction is often found in hypertension. Endothelium-derived hyperpolarization (EDH) plays a significant role in smaller renal arteries and arterioles, but its significance in vivo in hypertension is unresolved. The aim of this study was to characterize the EDH-induced renal vasodilation in normotensive and hypertensive rats during acute intrarenal infusion of ACh. Our hypothesis was that the increased renal vascular resistance (RVR) found early in hypertension would significantly correlate with reduced EDH-induced vasodilation. In isoflurane-anesthetized 12-week-old normo- and hypertensive rats blood pressure and renal blood flow (RBF) was measured continuously. RBF responses to acute intrarenal ACh infusions were measured before and after inhibition of NO and prostacyclin. Additionally, RVR was decreased or increased using inhibition or activation of adrenergic receptors or by use of papaverine and angiotensin II. Intrarenal infusion of ACh elicited a larger increase in RBF in hypertensive rats compared to normotensive rats suggesting that endothelial dysfunction is not present in 12-week-old hypertensive rats. The EDH-induced renal vasodilation (after inhibition of NO and prostacyclin) was similar between normo- and hypertensive rats. Reducing RVR by inhibition of α1 -adrenergic receptors significantly increased the renal EDH response in hypertensive rats, but a similar increase was found after activating α-adrenergic receptors using norepinephrine. The results show that renal EDH is present and functional in 12-week-old normo- and hypertensive rats. Interestingly, both activation and inactivation of α1 -adrenergic receptors elicited an increase in the renal EDH-induced vasodilation.

2.
Physiol Rep ; 7(7): e14049, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30968589

RESUMO

Diabetic patients suffer from both cardiac lipid accumulation and an increased risk of arrhythmias and sudden cardiac death. This correlation suggests a link between diabetes induced cardiac steatosis and electrical abnormalities, however, the underlying mechanism remains unknown. We previously showed that cardiac conduction velocity slows in Zucker diabetic fatty rats and in fructose-fat fed rats, models that both exhibit prominent cardiac steatosis. The aim of this study was to investigate whether acute cardiac lipid accumulation reduces conduction velocity per se. Cardiac lipid accumulation was induced acutely by perfusing isolated rat hearts with palmitate-glucose buffer, or subacutely by fasting rats overnight. Subsequently, longitudinal cardiac conduction velocity was measured in right ventricular tissue strips, and intramyocardial triglyceride and lipid droplet content was determined by thin layer chromatography and BODIPY staining, respectively. Perfusion with palmitate-glucose buffer significantly increased intramyocardial triglyceride levels compared to perfusion with glucose (2.16 ± 0.17 (n = 10) vs. 0.92 ± 0.33 nmol/mg WW (n = 9), P < 0.01), but the number of lipid droplets was very low in both groups. Fasting of rats, however, resulted in both significantly elevated intramyocardial triglyceride levels compared to fed rats (3.27 ± 0.43 (n = 10) vs. 1.45 ± 0.24 nmol/mg WW (n = 10)), as well as a larger volume of lipid droplets (0.60 ± 0.13 (n = 10) vs. 0.21 ± 0.06% (n = 10), P < 0.05). There was no significant difference in longitudinal conduction velocity between palmitate-glucose perfused and control hearts (0.77 ± 0.025 (n = 10) vs. 0.75 m/sec ± 0.029 (n = 9)), or between fed and fasted rats (0.75 ± 0.042 m/sec (n = 10) vs. 0.79 ± 0.047 (n = 10)). In conclusion, intramyocardial lipid accumulation does not slow cardiac longitudinal conduction velocity per se. This is true for both increased intramyocardial triglyceride content, induced by palmitate-glucose perfusion, and increased intramyocardial triglyceride and lipid droplet content, generated by fasting.

3.
Am J Physiol Renal Physiol ; 316(5): F769-F784, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30759020

RESUMO

Tubuloglomerular feedback and the myogenic mechanism form an ensemble in renal afferent arterioles that regulate single-nephron blood flow and glomerular filtration. Each mechanism generates a self-sustained oscillation, the mechanisms interact, and the oscillations synchronize. The synchronization generates a bimodal electrical signal in the arteriolar wall that propagates retrograde to a vascular node, where it meets similar electrical signals from other nephrons. Each signal carries information about the time-dependent behavior of the regulatory ensemble. The converging signals support synchronization of the nephrons participating in the information exchange, and the synchronization can lead to formation of nephron clusters. We review the experimental evidence and the theoretical implications of these interactions and consider additional interactions that can limit the size of nephron clusters. The architecture of the arterial tree figures prominently in these interactions.

4.
EuroIntervention ; 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30451687

RESUMO

AIMS: Patients with cyanotic congenital heart disease (CCHD) have been suggested to develop less atherosclerosis than the general population. This study aimed to evaluate the extent of coronary atherosclerosis in patients with CCHD using intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS). METHODS AND RESULTS: Fifteen patients with CCHD (women, 9; median age, 53 years) and 14 acyanotic controls (women, 6; median age, 53 years) were examined with IVUS-NIRS of the right coronary artery (RCA). The patients with CCHD presented with a larger RCA diameter than the controls (external-elastic-membrane diameter, 6.1 [4.8-6.7] vs. 4.7 [4.1-5.1] mm, respectively; p=0.01). No difference in area-stenosis was found between the patients and the controls (15.8% [12.3-19.7%] vs. 15.2% [9.5-18.8%]; p=0.87). The presence of lipid by NIRS was noted in 43% of patients with CCHD and in 92% of the controls; however, no differences in total or max-4-mm lipid-core-burden-index (LCBI) or in plasma lipid-profile were found. CONCLUSIONS: Patients with CCHD presented with larger coronary arteries than acyanotic controls. No difference in the degree of area-stenosis in the coronary arteries was found between the cyanotic and acyanotic patients; however, a lower proportion of patients with CCHD showed a positive LCBI.

5.
Int J Cardiol ; 2018 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-30228018

RESUMO

INTRODUCTION: Survival in patients with cyanotic congenital heart disease (CCHD) has improved dramatically. The result is an ageing population with risk of acquired heart disease. Previous small uncontrolled studies suggested that these patients are protected against the development of atherosclerosis. To test this hypothesis, we sought to determine the prevalence of subclinical atherosclerosis in a larger population of patients with CCHD. METHOD: We compared the prevalence of subclinical atherosclerosis in adult CCHD patients from Denmark, Sweden, Norway and Australia, with that in age-, sex-, smoking status-, and body mass index matched controls. Coronary artery atherosclerosis was assessed on computed tomography with coronary artery calcification (CAC) score. Subclinical atherosclerosis was defined by CAC-score > 0. Carotid artery atherosclerosis was evaluated using ultrasound by measuring carotid plaque thickness (cPT-max) and carotid intima media thickness (CIMT). Lipid status was evaluated as an important atherosclerotic risk factor. RESULTS: Seventy-four patients with CCHD (57% women, median age 49.5 years) and 74 matched controls (57% women, median age 50.0 years) were included. There were no differences between the groups in: CAC-score > 0 (21% vs. 19%, respectively; p = 0.8), carotid plaques (19% vs. 9%, respectively; p = 0.1), cPT-max (2.3 mm vs. 2.8 mm, respectively; p = 0.1) or CIMT (0.61 mm vs. 0.61 mm, respectively; p = 0.98). And further no significant differences in lipoprotein concentrations measured by ultracentrifugation. CONCLUSION: Young adults with CCHD have similar cardiovascular risk factor profiles and measures of subclinical atherosclerosis, compared with controls. Given their increasing life expectancies, athero-preventive strategies should be an important part of their clinical management.

6.
Physiol Rep ; 6(5)2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29504258

RESUMO

The effect of recombinant erythropoietin (rhEPO) on renal and systemic hemodynamics was evaluated in a randomized double-blinded, cross-over study. Sixteen healthy subjects were tested with placebo, or low-dose rhEPO for 2 weeks, or high-dose rhEPO for 3 days. Subjects refrained from excessive salt intake, according to instructions from a dietitian. Renal clearance studies were done for measurements of renal plasma flow, glomerular filtration rate (GFR) and the segmentel tubular handling of sodium and water (lithium clearance). rhEPO increased arterial blood pressure, total peripheral resistance, and renal vascular resistance, and decreased renal plasma flow in the high-dose rhEPO intervention and tended to decrease GFR. In spite of the decrease in renal perfusion, rhEPO tended to decrease reabsorption of sodium and water in the proximal tubule and induced a prompt decrease in circulating levels of renin and aldosterone, independent of changes in red blood cell mass, blood volumes, and blood pressure. We also found changes in biomarkers showing evidence that rhEPO induced a prothrombotic state. Our results suggest that rhEPO causes a direct downregulation in proximal tubular reabsorption that seems to decouple the activity of the renin-angiotensin-aldosterone system from changes in renal hemodynamics. This may serve as a negative feed-back mechanism on endogenous synthesis of EPO when circulating levels of EPO are high. These results demonstrates for the first time in humans a direct effect of rhEPO on renal hemodynamics and a decoupling of the renin-angiotensin-aldosterone system.

7.
Clin Sci (Lond) ; 132(4): 461-474, 2018 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-29436481

RESUMO

Abdominal obesity and/or a high intake of fructose may cause hypertension. K+ channels, Na/K-ATPase, and voltage-gated Ca2+ channels are crucial determinants of resistance artery tone and thus the control of blood pressure. Limited information is available on the role of K+ transporters in long-term diet-induced hypertension in rats. We hypothesized that a 28-week diet rich in fat, fructose, or both, will lead to changes in K+ transporter expression and function, which is associated with increased blood pressure and decreased arterial function. Male Sprague-Dawley (SD) rats received a diet containing normal chow (Control), high-fat chow (High Fat), high-fructose in drinking water (High Fructose), or a combination of high-fat and high-fructose diet (High Fat/Fruc) for 28 weeks from the age of 4 weeks. Measurements included body weight (BW), systolic blood pressure (SBP), mRNA expression of vascular K+ transporters, and vessel myography in small mesenteric arteries (SMAs). BW was increased in the High Fat and High Fat/Fruc groups, and SBP was increased in the High Fat/Fruc group. mRNA expression of small conductance calcium-activated K+ channel (SKCa), intermediate conductance calcium-activated K+ (IKCa), and Kir2.1 inward rectifier K+ channels were reduced in the High Fat/Fruc group. Reduced endothelium-derived hyperpolarization (EDH)-type relaxation to acetylcholine (ACh) was seen in the High Fat and High Fat/Fruc groups. Ba2+-sensitive dilatation to extracellular K+ was impaired in all the experimental diet groups. In conclusion, reduced expression and function of SKCa, IKCa, and Kir2.1 channels are associated with elevated blood pressure in rats fed a long-term High Fat/Fruc. Rats fed a 28-week High Fat/Fruc provide a relevant model of diet-induced hypertension.

8.
Ugeskr Laeger ; 179(45)2017 Nov 06.
Artigo em Dinamarquês | MEDLINE | ID: mdl-29108535

RESUMO

Over the last 35 years there has been an almost 50% increase in childhood obesity worldwide. Childhood obesity is associated with increased cardiovascular morbidity and mortality in adulthood, and in children with overweight or obesity pathologic changes have been found down to the age of two years. These changes are present in vasculature, heart and autonomic nervous system and affect blood pressure control. Overweight and obesity must be prevented, detected and treated at an early age, as even a small weight loss reduces the risk of cardiovascular disease significantly.

9.
Am J Physiol Renal Physiol ; 313(2): F351-F360, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28424208

RESUMO

Among solid organs, the kidney's vascular network stands out, because each nephron has two distinct capillary structures in series and because tubuloglomerular feedback, one of the mechanisms responsible for blood flow autoregulation, is specific to renal tubules. Tubuloglomerular feedback and the myogenic mechanism, acting jointly, autoregulate single-nephron blood flow. Each generates a self-sustained periodic oscillation and an oscillating electrical signal that propagates upstream along arterioles. Similar electrical signals from other nephrons interact, allowing nephron synchronization. Experimental measurements show synchronization over fields of a few nephrons; simulations based on a simplified network structure that could obscure complex interactions predict more widespread synchronization. To permit more realistic simulations, we made a cast of blood vessels in a rat kidney, performed micro-computed tomography at 2.5-µm resolution, and recorded three-dimensional coordinates of arteries, afferent arterioles, and glomeruli. Nonterminal branches of arcuate arteries form treelike structures requiring two to six bifurcations to reach terminal branches at the tree tops. Terminal arterial structures were either paired branches at the tops of the arterial trees, from which 52.6% of all afferent arterioles originated, or unpaired arteries not at the tree tops, yielding the other 22.9%; the other 24.5% originated directly from nonterminal arteries. Afferent arterioles near the corticomedullary boundary were longer than those farther away, suggesting that juxtamedullary nephrons have longer afferent arterioles. The distance separating origins of pairs of afferent arterioles varied randomly. The results suggest an irregular-network tree structure with vascular nodes, where arteriolar activity and local blood pressure interact.


Assuntos
Arteríolas/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Néfrons/irrigação sanguínea , Artéria Renal/diagnóstico por imagem , Microtomografia por Raio-X , Animais , Arteríolas/anatomia & histologia , Masculino , Modelos Anatômicos , Modelos Cardiovasculares , Ratos Sprague-Dawley , Artéria Renal/anatomia & histologia , Técnicas de Réplica
10.
Heart ; 103(12): 897-900, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28259844

RESUMO

Improved treatment options in paediatric cardiology and congenital heart surgery have resulted in an ageing population of patients with cyanotic congenital heart disease (CCHD). The risk of acquired heart disease such as atherosclerosis increases with age.Previous studies have speculated whether patients with CCHD are protected against atherosclerosis. Results have shown that the coronary arteries of patients with CCHD are free from plaques and stenosis. Decreased carotid intima-media thickness and low total plasma cholesterol may indicate a reduced risk of later development of atherosclerosis. However, the evidence is still sparse and questionable, and a reasonable explanation for the decreased risk of developing atherosclerosis in patients with CCHD is still missing.This review provides an overview of what is known about the prevalence and potential causes of the reduced risk of atherosclerosis in patients with CCHD.


Assuntos
Aterosclerose/epidemiologia , Cardiopatias Congênitas/complicações , Aterosclerose/etiologia , Saúde Global , Cardiopatias Congênitas/epidemiologia , Humanos , Prevalência
11.
PLoS Comput Biol ; 12(7): e1004922, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27447287

RESUMO

Through regulation of the extracellular fluid volume, the kidneys provide important long-term regulation of blood pressure. At the level of the individual functional unit (the nephron), pressure and flow control involves two different mechanisms that both produce oscillations. The nephrons are arranged in a complex branching structure that delivers blood to each nephron and, at the same time, provides a basis for an interaction between adjacent nephrons. The functional consequences of this interaction are not understood, and at present it is not possible to address this question experimentally. We provide experimental data and a new modeling approach to clarify this problem. To resolve details of microvascular structure, we collected 3D data from more than 150 afferent arterioles in an optically cleared rat kidney. Using these results together with published micro-computed tomography (µCT) data we develop an algorithm for generating the renal arterial network. We then introduce a mathematical model describing blood flow dynamics and nephron to nephron interaction in the network. The model includes an implementation of electrical signal propagation along a vascular wall. Simulation results show that the renal arterial architecture plays an important role in maintaining adequate pressure levels and the self-sustained dynamics of nephrons.


Assuntos
Arteríolas , Hemodinâmica/fisiologia , Rim , Modelos Biológicos , Algoritmos , Animais , Arteríolas/anatomia & histologia , Arteríolas/fisiologia , Biologia Computacional , Processamento de Imagem Assistida por Computador , Rim/anatomia & histologia , Rim/irrigação sanguínea , Rim/fisiologia , Néfrons/anatomia & histologia , Néfrons/irrigação sanguínea , Néfrons/fisiologia , Ratos , Artéria Renal/anatomia & histologia , Artéria Renal/fisiologia
12.
Physiol Rep ; 4(11)2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27255360

RESUMO

Mean arterial pressure (MAP) is surprisingly similar across different species of mammals, and it is, in general, not known which factors determine the arterial pressure level. Mammals often have a pronounced capacity for sustained physical performance. This capacity depends on the vasculature having a flow reserve that comes into play as tissue metabolism increases. We hypothesize that microvascular properties allowing for a large vascular flow reserve is linked to the level of the arterial pressure.To study the interaction between network properties and network inlet pressure, we developed a generic and parsimonious computational model of a bifurcating microvascular network where diameter and growth of each vessel evolves in response to changes in biomechanical stresses. During a simulation, the network develops well-defined arterial and venous vessel characteristics. A change in endothelial function producing a high precapillary resistance and thus a high vascular flow reserve is associated with an increase in network inlet pressure. Assuming that network properties are independent of body mass, and that inlet pressure of the microvascular network is a proxy for arterial pressure, the study provides a conceptual explanation of why high performing animals tend to have a high MAP.


Assuntos
Pressão Arterial/fisiologia , Hemodinâmica/fisiologia , Modelos Cardiovasculares , Animais , Microcirculação/fisiologia , Microvasos/fisiologia , Resistência Vascular/fisiologia
13.
Thorac Cardiovasc Surg ; 64(7): 569-574, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26501221

RESUMO

Background Cerebral hemodynamic disturbances in the peri- or postoperative period may contribute to postoperative cognitive dysfunction (POCD) in patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). We therefore examined dynamic cerebral autoregulation (dCA) post-CPB and changes in neurocognitive function in patients that had undergone CABG. Materials and Methods We assessed dCA by transfer function analysis of spontaneous oscillations between arterial blood pressure and middle cerebral artery blood flow velocity measured by transcranial Doppler ultrasound in eight patients 6 hours after the cessation of CPB; 10 healthy volunteers served as controls. Neurocognitive function was assessed by four specific tests 1 day prior to and 3 days after CPB. Results Even though patients exhibited systemic inflammation and anemic hypoxemia, dCA was similar to healthy volunteers (gain: 1.24 [0.94-1.49] vs. 1.22 [1.06-1.34] cm mm Hg-1 s-1, p = 0.97; phase: 0.33 [0.15-0.56] vs. 0.69 [0.50-0.77] rad, p = 0.09). Neurocognitive testing showed a perioperative decline in the Letter Digit Coding Score (p = 0.04), while weaker dCA was associated with a lower Stroop Color Word Test (rho = - 0.90; p = 0.01). Discussion and Conclusion We found no changes in dCA 6 hours after CPB. However, based on the data at hand, it cannot be ruled out that changes in dCA predispose to POCD, which calls for larger studies that assess the potential impact of dCA in the early postoperative period on POCD.


Assuntos
Ponte Cardiopulmonar/efeitos adversos , Circulação Cerebrovascular , Transtornos Cerebrovasculares/etiologia , Transtornos Cognitivos/etiologia , Cognição , Ponte de Artéria Coronária/efeitos adversos , Estenose Coronária/cirurgia , Artéria Cerebral Média/fisiopatologia , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/fisiopatologia , Transtornos Cerebrovasculares/psicologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Estenose Coronária/diagnóstico por imagem , Homeostase , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Teste de Stroop , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler Transcraniana , Adulto Jovem
14.
Blood Press Monit ; 21(2): 75-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26544524

RESUMO

OBJECTIVE: In the present hypothesis-generating study, we investigated whether spontaneous blood pressure oscillations are suppressed to lower frequencies, and whether abolished oscillations are associated with an adverse outcome in mechanically ventilated patients with sepsis. METHODS: We retrospectively subjected invasive steady-state blood pressure recordings from 65 mechanically ventilated patients with sepsis to spectral analysis. Modified spectral bands were visually identified by plotting spectral power against frequency. RESULTS: Modified middle-frequency and low-frequency (MF' and LF') oscillations were absent in 9% and 22% of the patients, respectively. In patients in whom spontaneous blood pressure oscillations were preserved, the MF' oscillations occurred at 0.021 Hz (median, interquartile range 0.013-0.030), whereas the LF' oscillations occurred at 0.009 Hz (median, interquartile range 0.006-0.010). The absence of LF' oscillations was associated with a higher 30-day mortality [50 vs. 18%, hazard ratio, 3.6 (95% confidence interval: 1.4-9.8), P=0.01]. CONCLUSION: Spontaneous blood pressure oscillations in mechanically ventilated septic patients may be suppressed to lower frequencies than previously reported for spontaneously breathing, healthy humans. Patients in whom the resultant changes in blood pressure (MF' and LF' oscillations) are abolished may have a higher risk of an adverse outcome. This may reflect suppression of the pressor area in the brainstem with subsequent sympathetic dysfunction.


Assuntos
Relógios Biológicos , Pressão Sanguínea , Respiração Artificial , Sepse/fisiopatologia , Sepse/terapia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Clin Physiol Funct Imaging ; 36(6): 490-496, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26017052

RESUMO

Previous studies have demonstrated that dynamic cerebral autoregulation to spontaneous fluctuations in blood pressure is enhanced following lipopolysaccharide (LPS) infusion, a human experimental model of early sepsis, whereas by contrast it is impaired in patients with severe sepsis or septic shock. In this study, we hypothesized that this pattern of response would be identical during induced changes in blood pressure. Dynamic cerebral autoregulation was assessed in nine healthy volunteers and six septic patients. The healthy volunteers underwent a 4-h intravenous infusion of LPS (total dose: 2 ng kg-1 ). Mean arterial blood pressure (MAP, arterial transducer) and middle cerebral artery blood flow velocity (MCAv, transcranial Doppler ultrasound) were recorded continuously during thigh-cuff deflation-induced changes in MAP for the determination of a modified rate of regulation (RoR). This was performed before and after LPS infusion in healthy volunteers, and within 72 h following clinical diagnosis of sepsis in patients. In healthy volunteers, thigh-cuff deflation caused a MAP reduction of 16 (13-20) % at baseline and 18 (16-20) % after LPS, while the MAP reduction was 12 (11-13) % in patients (P<0·05 versus volunteers at baseline; P<0·01 versus volunteers after LPS). The corresponding RoR values increased from 0·46 (0·31-0·49) s-1 at baseline to 0·58 (0·36-0·74) s-1 after LPS (P<0·05) in healthy volunteers, whereas they were similar to values observed in patients [0·43 (0·36-0·52) s-1 ; P = 0·91 versus baseline; P = 0·14 versus LPS]. While our findings support the concept that dynamic cerebral autoregulation is enhanced during the very early stages of sepsis, they remain inconclusive with regard to more advanced stages of disease, because thigh-cuff deflation failed to induce sufficient MAP reductions in patients.


Assuntos
Pressão Arterial , Circulação Cerebrovascular , Artéria Cerebral Média/fisiopatologia , Sepse/fisiopatologia , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Homeostase , Humanos , Lipopolissacarídeos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Sepse/induzido quimicamente , Sepse/diagnóstico por imagem , Fatores de Tempo , Ultrassonografia Doppler Transcraniana , Adulto Jovem
16.
Pflugers Arch ; 468(4): 541-50, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26658945

RESUMO

Renal autoregulation protects glomerular capillaries against increases in renal perfusion pressure (RPP). In the mesentery, both L- and T-type calcium channels are involved in autoregulation. L-type calcium channels participate in renal autoregulation, but the role of T-type channels is not fully elucidated due to lack of selective pharmacological inhibitors. The role of T- and L-type calcium channels in the response to acute increases in RPP in T-type channel knockout mice (CaV3.1) and normo- and hypertensive rats was examined. Changes in afferent arteriolar diameter in the kidneys from wild-type and CaV3.1 knockout mice were assessed. Autoregulation of renal blood flow was examined during acute increases in RPP in normo- and hypertensive rats under pharmacological blockade of T- and L-type calcium channels using mibefradil (0.1 µM) and nifedipine (1 µM). In contrast to the results from previous pharmacological studies, genetic deletion of T-type channels CaV3.1 did not affect renal autoregulation. Pharmacological blockade of T-type channels using concentrations of mibefradil which specifically blocks T-type channels also had no effect in wild-type or knockout mice. Blockade of L-type channels significantly attenuated renal autoregulation in both strains. These findings are supported by in vivo studies where blockade of T-type channels had no effect on changes in the renal vascular resistance after acute increases in RPP in normo- and hypertensive rats. These findings show that genetic deletion of T-type channels CaV3.1 or treatment with low concentrations of mibefradil does not affect renal autoregulation. Thus, T-type calcium channels are not involved in renal autoregulation in response to acute increases in RPP.


Assuntos
Canais de Cálcio Tipo T/metabolismo , Homeostase , Rim/metabolismo , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo T/genética , Deleção de Genes , Rim/irrigação sanguínea , Rim/fisiologia , Mibefradil/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Circulação Renal
17.
Biomed Opt Express ; 6(12): 5055-62, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26713217

RESUMO

Laminar flow in arteries causes streaming and uneven distribution of infused agents within the organ. This may lead to misinterpretation of experimental results and affect treatment outcomes. We monitor dynamical changes of superficial cortical blood flow in the rat kidney following different routes of administration of the vasoconstrictor angiotensin II. Our analysis reveals the appearance of large scale oscillations of the blood flow caused by inhomogeneous intra organ drug distribution.

18.
Cardiovasc Diabetol ; 14: 87, 2015 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-26169175

RESUMO

BACKGROUND: Type 2 diabetes is associated with abnormal electrical conduction and sudden cardiac death, but the pathogenic mechanism remains unknown. This study describes electrophysiological alterations in a diet-induced pre-diabetic rat model and examines the underlying mechanism. METHODS: Sprague-Dawley rats were fed either high-fat diet and fructose water or normal chow and water for 6 weeks. The electrophysiological properties of the whole heart was analyzed by in vivo surface ECG recordings, as wells as ex vivo in Langendorff perfused hearts during baseline, ischemia and reperfussion. Conduction velocity was examined in isolated tissue strips. Ion channel and gap junction conductances were analyzed by patch-clamp studies in isolated cardiomyocytes. Fibrosis was examined by Masson's Trichrome staining and thin-layer chromatography was used to analyze cardiac lipid content. Connexin43 (Cx43) expression and distribution was examined by western blotting and immunofluorescence respectively. RESULTS: Following 6 weeks of feeding, fructose-fat fed rats (FFFRs) showed QRS prolongation compared to controls (16.1 ± 0.51 (n = 6) vs. 14.7 ± 0.32 ms (n = 4), p < 0.05). Conduction velocity was slowed in FFFRs vs. controls (0.62 ± 0.02 (n = 13) vs. 0.79 ± 0.06 m/s (n = 11), p < 0.05) and Langendorff perfused FFFR hearts were more prone to ventricular fibrillation during reperfusion following ischemia (p < 0.05). The patch-clamp studies revealed no changes in Na(+) or K(+) currents, cell capacitance or gap junctional coupling. Cx43 expression was also unaltered in FFFRs, but immunofluorescence demonstrated an increased fraction of Cx43 localized at the intercalated discs in FFFRs compared to controls (78 ± 3.3 (n = 5) vs. 60 ± 4.2 % (n = 6), p < 0.01). No fibrosis was detected but FFFRs showed a significant increase in cardiac triglyceride content (1.93 ± 0.19 (n = 12) vs. 0.77 ± 0.13 nmol/mg (n = 12), p < 0.0001). CONCLUSION: Six weeks on a high fructose-fat diet cause electrophysiological changes, which leads to QRS prolongation, decreased conduction velocity and increased arrhythmogenesis during reperfusion. These alterations are not explained by altered gap junctional coupling, Na(+), or K(+) currents, differences in cell size or fibrosis.


Assuntos
Arritmias Cardíacas/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Estado Pré-Diabético/fisiopatologia , Animais , Conexina 43/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Eletrocardiografia , Frutose , Junções Comunicantes/metabolismo , Masculino , Contração Miocárdica , Reperfusão Miocárdica , Técnicas de Patch-Clamp , Canais de Potássio/metabolismo , Ratos , Ratos Sprague-Dawley , Canais de Sódio/metabolismo , Triglicerídeos/metabolismo
19.
Clin Exp Pharmacol Physiol ; 42(7): 740-6, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25966743

RESUMO

Vasopressor support is used widely for maintaining vital organ perfusion pressure in septic shock, with implications for dynamic cerebral autoregulation (dCA). This study investigated whether a noradrenaline-induced steady state increase in mean arterial blood pressure (MAP) would enhance dCA following lipopolysaccharide (LPS) infusion, a human-experimental model of the systemic inflammatory response during early sepsis. The dCA in eight healthy males was examined prior to and during an intended noradrenaline-induced MAP increase of approximately 30 mmHg. This was performed at baseline and repeated after a 4-h intravenous LPS infusion. The assessments of dCA were based on transfer function analysis of spontaneous oscillations between MAP and middle cerebral artery blood flow velocity measured by transcranial Doppler ultrasound in the low frequency range (0.07-0.20 Hz). Prior to LPS, noradrenaline administration was associated with a decrease in gain (1.18 (1.12-1.35) vs 0.93 (0.87-0.97) cm/mmHg per s; P < 0.05) with no effect on phase (0.71 (0.93-0.66) vs 0.94 (0.81-1.10) radians; P = 0.58). After LPS, noradrenaline administration changed neither gain (0.91 (0.85-1.01) vs 0.87 (0.81-0.97) cm/mmHg per s; P = 0.46) nor phase (1.10 (1.04-1.30) vs 1.37 (1.23-1.51) radians; P = 0.64). The improvement of dCA to a steady state increase in MAP is attenuated during an LPS-induced systemic inflammatory response. This may suggest that vasopressor treatment with noradrenaline offers no additional neuroprotective effect by enhancing dCA in patients with early sepsis.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Homeostase/efeitos dos fármacos , Norepinefrina/farmacologia , Sepse/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Lipopolissacarídeos/farmacologia , Masculino , Norepinefrina/administração & dosagem , Sepse/induzido quimicamente , Adulto Jovem
20.
Am J Physiol Renal Physiol ; 308(8): F867-77, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25656368

RESUMO

Glucagon-like peptide (GLP)-1 has a range of extrapancreatic effects, including renal effects. The mechanisms are poorly understood, but GLP-1 receptors have been identified in the kidney. However, the exact cellular localization of the renal receptors is poorly described. The aim of the present study was to localize renal GLP-1 receptors and describe GLP-1-mediated effects on the renal vasculature. We hypothesized that renal GLP-1 receptors are located in the renal microcirculation and that activation of these affects renal autoregulation and increases renal blood flow. In vivo autoradiography using (125)I-labeled GLP-1, (125)I-labeled exendin-4 (GLP-1 analog), and (125)I-labeled exendin 9-39 (GLP-1 receptor antagonist) was performed in rodents to localize specific GLP-1 receptor binding. GLP-1-mediated effects on blood pressure, renal blood flow (RBF), heart rate, renin secretion, urinary flow rate, and Na(+) and K(+) excretion were investigated in anesthetized rats. Effects of GLP-1 on afferent arterioles were investigated in isolated mouse kidneys. Specific binding of (125)I-labeled GLP-1, (125)I-labeled exendin-4, and (125)I-labeled exendin 9-39 was observed in the renal vasculature, including afferent arterioles. Infusion of GLP-1 increased blood pressure, RBF, and urinary flow rate significantly in rats. Heart rate and plasma renin concentrations were unchanged. Exendin 9-39 inhibited the increase in RBF. In isolated murine kidneys, GLP-1 and exendin-4 significantly reduced the autoregulatory response of afferent arterioles in response to stepwise increases in pressure. We conclude that GLP-1 receptors are located in the renal vasculature, including afferent arterioles. Activation of these receptors reduces the autoregulatory response of afferent arterioles to acute pressure increases and increases RBF in normotensive rats.


Assuntos
Peptídeo 1 Semelhante ao Glucagon/metabolismo , Rim/irrigação sanguínea , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Receptores de Glucagon/metabolismo , Circulação Renal , Animais , Arteríolas/metabolismo , Autorradiografia , Pressão Sanguínea , Exenatida , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1 , Frequência Cardíaca , Homeostase , Imuno-Histoquímica , Camundongos Endogâmicos C57BL , Microcirculação , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Peptídeos/farmacologia , Potássio/sangue , Potássio/urina , Ratos Sprague-Dawley , Ratos Wistar , Receptores de Glucagon/agonistas , Circulação Renal/efeitos dos fármacos , Eliminação Renal , Renina/sangue , Transdução de Sinais , Sódio/sangue , Sódio/urina , Fatores de Tempo , Urodinâmica , Peçonhas/farmacologia
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