Vascular Reactivity In Response Research Articles

Pulse transit time as an index of vascular reactivity

Pulse transit time (PTT) is a non-invasive method for measuring arterial compliance and stiffness, which are excellent predictors of cardiovascular disease. This study aims to determine whether PTT can be used to precisely monitor vascular reactivity in response to changes in hand posture and whether the digital pulse wave index of time-to-maximum slope (TMS) is a suitable alternative to PTT. Fifteen healthy, 22-year-old males participated in the study. The PTT was monitored from electrocardiogram (ECG) to digital pulse wave (DPW), and the morphological variable TMS of the DPW wave was estimated in beat-tobeat intervals for the individuals while their arms were raised and dropped. The results demonstrated that the PTT increased significantly with elevating the hand, and the correlation probability of the second polynomial fitness equation neared infinite. In addition, the PTT significantly correlated (P<0.007) with the TMS of the DPW throughout the hand motions. The data indicate that PTT can represent local vascular responses during changes in hand position. In this study, we developed a new DPW index and suggest a TMS index as a viablesubstitute for PTT.Keywords: Cardiovascular, Electrocardiography, Pulse

Prevention of vasoplegia with CytoSorb in heart failure patients undergoing cardiac surgery (CytoSorb-HF trial): protocol for a randomised controlled trial

IntroductionVasoplegia is a common complication after cardiac surgery and is associated with poor prognosis. It is characterised by refractory hypotension despite normal or even increased cardiac output. The pathophysiology is...

Measurement of Endothelium-dependent Vasorelaxation in the Mouse Thoracic Aorta using Tensometric Small Volume Chamber Myography.

Small volume chamber tensometric myography is a commonly used technique to evaluate the vascular contractility of small and large blood vessels in laboratory animals and small arteries isolated from human tissue. The technique allows researchers to maintain isolated blood vessels in a tightly controlled and standardized (near-physiological) setting, with the option of adjusting to various environmental factors, while challenging the isolated vessels with different pharmacological agents that can induce vasoconstriction or vasodilation. The myograph chamber also provides a platform to measure vascular reactivity in response to various hormones, inhibitors, and agonists that may impact the function of smooth muscle and endothelial layers separately or simultaneously. The blood vessel wall is a complex structure consisting of three different layers: the intima (endothelial layer), media (smooth muscle and elastin fibers), and adventitia (collagen and other connective tissue). To gain a clear understanding of the functional properties of each layer, it is critical to have access to an experimental platform and system that would allow for a combinational approach to study all three layers simultaneously. Such an approach demands access to a semi-physiological condition that would mimic the in vivo environment in an ex vivo setting. Small volume chamber tensometric myography has provided an ideal environment to evaluate the impact of environmental cues, experimental variables, or pharmacological agonists and antagonists on vascular properties. For many years, scientists have used the tensometric myograph technique to measure endothelial function and smooth muscle contractility in response to different agents. In this report, a small volume chamber tensometric myograph system is used to measure endothelial function in the isolated mouse aorta. This report focuses on how small volume chamber tensometric myography can be used to evaluate the functional integrity of the endothelium in small segments of a large artery such as the thoracic aorta.

Spironolactone prevents L‐type CaV1.2 potentiation and chronic vasoconstriction during diabetic hyperglycemia

Vascular complications are major causes of morbidity and mortality in diabetic patients. Recently, our group identified a novel purinergic signaling pathway involving the P2Y11/AKAP5/AC5/PKA/CaV1.2 protein network in arterial myocytes. This purinergic complex is activated by the release of nucleotides (e.g. ATP) to the extracellular space in response to hyperglycemic conditions, which promotes L‐type CaV1.2 potentiation and vasoconstriction. Pannexin 1 (Panx1) is a channel that mediates ATP efflux, thus inducing purinergic signaling activation. However, whether Panx1 forms part of the novel purinergic signaling complex that regulates L‐type CaV1.2 activity and vascular reactivity during diabetic hyperglycemia is unknown. Here, we find that Panx1 is in complex with P2Y11, AKAP5, AC5, PKA and CaV1.2 in arterial myocytes. This protein complex is strengthened upon elevated glucose (HG) treatment. However, the Panx1 inhibitor spironolactone prevented the HG‐induced strengthening of the complex. Spironolactone also blocked cAMP production, L‐type CaV1.2 potentiation and sustained vasoconstriction in response to elevated glucose. Consistent with a role for Panx1 upstream of P2Y11, spironolactone failed to prevent HG‐induced vasoconstriction upon addition of the specific P2Y11 agonist NF546. Altogether, these data suggest that Panx1 is part of the P2Y11/AKAP5/AC5/PKA/CaV1.2 signaling module in arterial myocytes. This Panx1‐led complex modulates L‐type CaV1.2 activity and vascular reactivity in response to diabetic hyperglycemic conditions. Thus, Panx1 could be a new therapeutic target to treat vascular complications during diabetes.

Evaluation of the effects of mild aerobic exercise and Losartan treatment on aortic endothelial function in a mouse model of Marfan syndrome

Marfan Syndrome (MFS) is an autosomal dominant disorder in a family of connective tissue disorders. It is well established that vascular complications in MFS is associated with endothelial dysfunction, leading to a whole host of phenotypic abnormalities. A predominant clinical concern is the development of aortic aneurysm with possible subsequent dissection and rupture.In the present study, we have utilized the ex‐vivo isometric myograph technique to examine the reactivity of isolated aortic segments from control and MFS mice in the presence or absence of different in‐vivo treatments and pharmacological agents. More specifically, we assessed the impact of mild aerobic exercise on endothelial function, aortic root growth, and aortic wall elasticity in a well‐established mouse model of MFS‐associated aortic aneurysm with special focus on nitric oxide production. Nitric oxide, as frequently demonstrated in the literature, plays a crucial role in maintaining normal vascular structure and function. In the current study, we examine the potential effects of mild aerobic exercise in the absence or presence of a potent general inhibitor of nitric oxide synthase (NOS), N5‐[imino(nitroamino)methyl]‐L‐ornithine, methyl ester, monohydrochloride (L‐NAME) on aortic contraction and endothelium‐mediated vasorelaxation in 6‐month‐old MFS mice carrying Fbn1 mutation and age‐ and sex‐matched C57BL/6J wildtype (WT) controls (male and females).At 4‐6 weeks of age, MFS mice were subjected to daily treadmill exercise (at 55% of VO2max, 8m/min, 30min/day, 5days/week) and/or drug treatment for a duration of 5 months. At 6 months of age, 2mm descending aortic rings were collected and mounted onto a small chamber myograph in order to measure the vascular reactivity in response to different vasoconstricting and vasodilating agents.Our study shows marked reduction in the phenylephrine (PE)‐induced contraction [50 µmol] and aortic wall rupture point in MFS mice aorta as compared to healthy controls. Treatment with either aerobic exercise or Losartan, an angiotensin II type 1 receptor blocker (ARB), rescued rupture point closer to WT control, but led to further decrease in PE contraction compared to MFS sedentary mice, mainly due to further increase in NO production within the aortic wall. In addition, direct inhibition of NO production via L‐Name, a nitric oxide synthase (NOS) inhibitor, effectively reduced PE‐induced contraction in MFS mice aorta that were subjected to exercise or Losartan treatment, further confirming that both exercise and Losartan treatment cause an increase in NO production.This study highlights the importance of endothelial function in improving the function and structure of aortic wall during the progression of aortic aneurysm in MFS mice and establish the notion that the protective effects of aerobic exercise and Losartan treatments are potentially through improving endothelium‐mediated nitric oxide production.

TRPV4-dependent signaling mechanisms in systemic and pulmonary vasculature.

The delicate balance between constrictor and dilator mechanisms is a vital determinant of blood pressure and blood flow. The maintenance of this balance requires constant communication between different cell-types in the vascular wall. In this regard, the transient receptor potential vanilloid type 4 (TRPV4) ion channel, a Ca2+-permeable non-selective cation channel, has emerged as a crucial regulator of Ca2+-mediated changes in vascular reactivity. Recent studies suggest that TRPV4 channels regulate vasoconstriction and arterial pressure in the systemic and pulmonary vasculature. New emerging data support a dilatory role of endothelial TRPV4 channels, and both constrictor and dilator roles of smooth muscle TRPV4 channels. Moreover, TRPV4 channel activity has been implicated in physiological functions of vascular support cells, such as fibroblasts and pericytes, to assist the sustenance of vascular reactivity in response to changes in intravascular pressure or external stimulation. Importantly, a growing body of evidence connects abnormal TRPV4 channel activity to multiple vascular disorders. This chapter will review the current literature on the cell-type specific roles of vascular TRPV4 channels in regulating physiological function. Additionally, we summarize our understanding of the contribution of abnormal TRPV4 channel activity to various vascular disorders.

Early passive mobilization increases vascular reactivity response in critical patients with sepsis: a quasi-experimental study

Early passive mobilization increases vascular reactivity response in critical patients with sepsis: a quasi-experimental study

Medullary vein architecture modulates the white matter BOLD cerebrovascular reactivity signal response to CO2: Observations from high-resolution T2* weighted imaging at 7T

Brain stress testing using blood oxygenation level-dependent (BOLD) MRI to evaluate changes in cerebrovascular reactivity (CVR) is of growing interest for evaluating white matter integrity. However, even under healthy conditions, the white matter BOLD-CVR response differs notably from that observed in the gray matter. In addition to actual arterial vascular control, the venous draining topology may influence the WM-CVR response leading to signal delays and dispersions. These types of alterations in hemodynamic parameters are sometimes linked with pathology, but may also arise from differences in normal venous architecture. In this work, high-resolution T2*weighted anatomical images combined with BOLD imaging during a hypercapnic breathing protocol were acquired using a 7 tesla MRI system. Hemodynamic parameters including base CVR, hemodynamic lag, lag-corrected CVR, response onset and signal dispersion, and finally ΔCVR (corrected CVR minus base CVR) were calculated in 8 subjects. Parameter maps were spatially normalized and correlated against an MNI-registered white matter medullary vein atlas. Moderate correlations (Pearson's rho) were observed between medullary vessel frequency (MVF) and ΔCVR (0.52; 0.58 for total WM), MVF and hemodynamic lag (0.42; 0.54 for total WM), MVF and signal dispersion (0.44; 0.53 for total WM), and finally MVF and signal onset (0.43; 0.52 for total WM). Results indicate that, when assessed in the context of the WM venous architecture, changes in the response shape may only be partially reflective of the actual vascular reactivity response occurring further upstream by control vessels. This finding may have implications when attributing diseases mechanisms and/or progression to presumed impaired WM BOLD-CVR.

Glu298Asp (rs1799983) Polymorphism Influences Postprandial Vascular Reactivity and the Insulin Response to Meals of Varying Fat Composition in Postmenopausal Women: Findings from the Randomized, Controlled Dietary Intervention and VAScular function (DIVAS)-2 Study

Previous acute studies suggest the Glu298Asp polymorphism (rs1799983) may influence vascular reactivity in response to long-chain n-3 PUFA intake. However, the effects of this genotype on postprandial vascular function after meals rich in SFAs, n-6 PUFAs, and MUFAs are unclear. This study determined the impact of the Glu298Asp polymorphism on changes in vascular function and cardiometabolic risk biomarkers in response to sequential meals of varying fat composition. In a randomized, double-blind, crossover, acute study, 32 postmenopausal women (mean±SD age: 58±5y; BMI: 25.9±4.1kg/m2) consumed mixed meals (breakfast: 0min, 50g fat; lunch: 330min, 30g fat) containing SFAs, n-6 PUFAs, or MUFAs on 3 occasions. Blood samples for cardiometabolic disease risk markers and real-time measures of vascular reactivity [including flow-mediated dilatation (FMD; primary outcome)] were collected/performed before and regularly for 480min after breakfast. Participants were retrospectively genotyped for the Glu298Asp (rs1799983) polymorphism. Data were analyzed using linear mixed models. For the postprandial %FMD response, a test fat × genotype interaction was observed for the AUC (P=0.019) but not incremental AUC (IAUC), with the AUC being ∼24% greater after MUFA- than after SFA- and n-6 PUFA-rich meals in the Glu298 homozygotes (P≤0.026). Test fat × genotype interactions were also evident for postprandial insulin (P≤0.005), with the MUFA-rich meals demonstrating significantly higher AUC (12.8%/14.9%), IAUC (14.6%/20.0%), and maximum concentration (20.0%/34.5%) than the SFA- and n-6 PUFA-rich meals, respectively, in Asp298 carriers (P<0.05). Genotype did not influence other study outcome measures in response to the test fats. Our findings suggest the Glu298Asp polymorphism may represent a potential determinant of the inter-individual variability in postprandial responsiveness of %FMD and insulin to acute meal fat composition in postmenopausal women. Further studies are required to confirm these observations.This trial was registered at clinicaltrials.gov as NCT02144454.

Differential Mesenteric Venous and Arterial Vascular Reactivity to Adenosine between Rats, Dogs, Mini‐pigs, and Human

It is well established that adenosine induces arterial vasodilation in various vascular beds. However, its effect on the venous circulation is still largely unknown. The splanchnic system receives approximately 25% of cardiac output (CO) and contains approximately 20% of total blood volume. Mesenteric (part of splanchnic system, o. d. 150–250 μm) arteries (MA) and their adjacent veins (MV) from rats, dogs, mini‐pigs and humans were isolated and mounted on a myograph (DMT Technology, USA). Vessels were preconstricted with 1 μM phenylephrine (PE) for arteries and prostaglandin F2α (PGF2α) for veins. Cumulative concentrations of 5’‐N‐Ethylcarboxamidoadenosine (NECA, 10−11 – 10−5 M), a non‐specific adenosine agonist, were applied and evaluated. Tension development was normalized to the tension induced by PE/PGF2α as %. NECA induced a concentration dependent arterial vasodilation in all 3 animals and human MA (Fig. 1). The effects were very similar in all 3 animals (maximum of 91.09±10.94% to 93.88±1.93%), however human responses were less pronounced (maximum of 59.14±4.61%). Interestingly, veins from all species responded to NECA very differently (Fig. 2). MVs from rats were the only vessels that constricted strongly in response to NECA (182.94±17.52% of pre‐constriction), which has not been previously reported (Figs. 2– 3). NECA induced vasodilation in MV from the other species varied. NECA induced vasodilation in MV from dogs were similar to MA at high concentrations (Fig. 6, 10−8 M and above). However, MV from mini‐pig (Fig. 5) and human (Fig. 6) responses were minimal (Fig. 2, maximum of 24.56±14.67% in mini‐pig and 33.54±9.61% relaxation in human) compared to 92.93±2.26% relaxation in dogs. In conclusion, although mesenteric arterial vascular reactivity responds similarly to adenosine among species, mesenteric venous vascular reactivity responses varied greatly to adenosine among species. MVs from rats were the only vessel constricted strongly in response to NECA. Caution is advised when choosing animal models for studying vascular reactivity.Figure 1Figure 2Figure 3Figure 4Figure 5Figure 6

Autonomically-mediated decrease in microvascular blood flow due to mental stress and pain in sickle cell disease: A target for neuromodulatory interventions

Pain and vaso-occlusive crises (VOC) are hallmark complications of sickle cell disease (SCD) and result in significant physical and psychosocial impairment. The variability in SCD pain frequency and triggers for the transition from steady state to VOC are not well understood. This paper summarizes the harmful physiological effects of pain and emotional stressors on autonomically-mediated vascular function in individuals with SCD and the effects of a cognitive, neuromodulatory intervention (i.e. hypnosis) on microvascular blood flow. We reviewed recent studies from the authors’ vascular physiology laboratory that assessed microvascular responses to laboratory stressors in individuals with SCD. Results indicate that participants with SCD exhibit marked neurally mediated vascular reactivity in response to pain, pain-related fear, and mental stress. Further, pilot study results show that engagement in hypnosis may attenuate harmful microvascular responses to pain. The collective results demonstrate that autonomically-mediated vascular responses to pain and mental stress represent an important SCD intervention target. This ongoing work provides physiological justification for the inclusion of cognitive, neuromodulatory and complementary treatments in SCD disease management and may inform the development of targeted, integrative interventions that prevent the enhancement of autonomic vascular dysfunction in SCD.

Assessment of health status during exposure to cigarette smoke using blood chemistry, lung tissue histology and myocardial metabolism

Background and Objectives: Cardiorespiratory function is critical to well-being. The effect of cigarette smoke exposure (CSE) as a pollutant on human health is of great interest and requires an adequate investigation in order to reduce the burden of its complications. This study was designed to investigate the effect of cigarette smoke on cardiovascular function and airway muscle functional anatomy using an experimental setup. Materials and Methods: Twenty adult male guinea pigs were grouped into four different groups and exposed to different concentrations of cigarette smoke. On the 12th week of exposure, blood pressure parameters were determined with the aid of a pressure transducer connected to a PowerLab data acquisition syste m. Vascular reactivity was also measured in relation to norepinephrine (NE), acetylcholine (ACh), and sodium nitroprusside (SNP). Myocardial oxygen demand (MOD) and baroreceptor reflex sensitivity were equally evaluated. Animals were sacrificed through cervical dislocation, and the lung and trachea were har vested for histological studies. Results: Cigarette smoke significantly decreased blood pressure and heart rate (HR), baroreceptor sensitivity, and MOD (P 0.05). Red blood cell and platelet concentration as well as sodium and calcium level in the blood were all increased at high dose of exposure. Conclusion: CSE resulted in alteration in histological architecture of the lungs and trachea. CSE decreased blood pressure, baroreflex sensitivity, MOD, and vascular reactivity response of MABP to ACh and SNP and increased HR and vascular reactivity response to NE. Furthermore, it also negatively altered the normal architecture of the lung and trachea.

Kallikrein-kinin system and oxidative stress in cisplatin-induced ovarian toxicity

Kallikrein-kinin system (KKS) is involved in vascular reactivity and inflammatory response to cytotoxic drugs. Since cisplatin is a widely used chemotherapy and its cytotoxic mechanism can trigger inflammation and oxidative damage, in this work we evaluated the role of KKS in an animal model of cisplatin-induced ovarian toxicity. Biomarkers of ovarian stem cells, activity of KKS, inflammation and oxidative damage were measured in ovarian tissue of C57BL/6 female mice treated with vehicle or cisplatin (2.5 mg/kg). Cisplatin group presented greater number of atretic follicles, and lower numbers of antral and total viable follicles. Ki67, DDX4 and OCT-4 markers were similar between groups. Cisplatin triggered plasma and ovarian tissue kallikrein generation; and increased expression of bradykinin receptors B1 and B2. Neutrophil and macrophage infiltration markers increased. Superoxide anion generation also increased, while reduced glutathione levels decreased. These results suggest that KKS is activated and contributes to ovarian injury during cisplatin treatment.

Vasoresponsiveness in patients with heart failure (VASOR): protocol for a prospective observational study

BackgroundVasoplegia is a severe complication which may occur after cardiac surgery, particularly in patients with heart failure. It is a result of activation of vasodilator pathways, inactivation of vasoconstrictor pathways and the resistance to vasopressors. However, the precise etiology remains unclear. The aim of the Vasoresponsiveness in patients with heart failure (VASOR) study is to objectify and characterize the altered vasoresponsiveness in patients with heart failure, before, during and after heart failure surgery and to identify the etiological factors involved.MethodsThis is a prospective, observational study conducted at Leiden University Medical Center. Patients with and patients without heart failure undergoing cardiac surgery on cardiopulmonary bypass are enrolled. The study is divided in two inclusion phases. During phase 1, 18 patients with and 18 patients without heart failure are enrolled. The vascular reactivity in response to a vasoconstrictor (phenylephrine) and a vasodilator (nitroglycerin) is assessed in vivo on different timepoints. The response to phenylephrine is assessed on t1 (before induction), t2 (before induction, after start of cardiotropic drugs and/or vasopressors), t3 (after induction), t4 (15 min after cessation of cardiopulmonary bypass) and t5 (1 day post-operatively). The response to nitroglycerin is assessed on t1 and t5. Furthermore, a sample of pre-pericardial fat tissue, containing resistance arteries, is collected intraoperatively. The ex vivo vascular reactivity is assessed by constructing concentrations response curves to various vasoactive substances using isolated resistance arteries. Next, expression of signaling proteins and receptors is assessed using immunohistochemistry and mRNA analysis. Furthermore, the groups are compared with respect to levels of organic compounds that can influence the cardiovascular system (e.g. copeptin, (nor)epinephrine, ANP, BNP, NTproBNP, angiotensin II, cortisol, aldosterone, renin and VMA levels). During inclusion phase 2, only the ex vivo vascular reactivity test is performed in patients with (N = 12) and without heart failure (N = 12).DiscussionUnderstanding the difference in vascular responsiveness between patients with and without heart failure in detail, might yield therapeutic options or development of preventive strategies for vasoplegia, leading to safer surgical interventions and improvement in outcome.Trial registrationThe Netherlands Trial Register (NTR), NTR5647. Registered 26 January 2016.

A Pilot Study of Changes in Medial Temporal Lobe Fractional Amplitude of Low Frequency Fluctuations after Sildenafil Administration in Patients with Alzheimer's Disease.

Alzheimer's disease (AD) is the most common cause of neurodegenerative cognitive impairment, defined by abnormal accumulations of amyloid-β and tau. Approaches directly targeting these proteins have not resulted in a disease modifying therapy. Neurovascular unit dysfunction is a feature of AD offering an alternative target for intervention. Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, improves cognitive functioning in mouse models of AD. Recent work in AD patients has demonstrated increased cerebral blood flow, as well as brain oxygen utilization after a single dose of sildenafil. Its effect on nitric oxide-cGMP signaling may have downstream effects on neuroplasticity, amyloid-β processing, and improved neurovascular unit function. Fractional amplitude of low frequency fluctuations (fALFF) assesses spontaneous neural activity via resting state fMRI BOLD signal (0.01-0.08 or 0.10 Hz). In AD, other assessments have revealed increased fALFF in hippocampi and parahippocampal gyri. Here, we examined the effects of a single dose of sildenafil on fALFF in a cohort of 10 AD patients. We found a decrease (p < 0.03, α= 0.05) in fALFF an hour after sildenafil administration in the right hippocampus. Additionally, cerebral vascular reactivity in response to carbon dioxide inhalation, a measure of neural vascular reserve previously collected on most of these participants, was not significantly correlated with this decrease, implying that change in fALFF may not have been solely due to altered vascular reactivity to CO2. We demonstrate that in patients with AD, hippocampal fALFF decreases in response to sildenafil, suggesting a normalization. These findings support further investigation into the effects of sildenafil in AD.

AUDA as a modulator of lipid profile and endothelial function in diet induced hypercholesterolemia in rats

Background: Epoxyeicosatrienoic acids (EETs) are cytochrome P450 metabolites of arachidonic acid produced by the vascular endothelium and act as important regulators of vascular tone. Objectives: to study the effect of soluble epoxide hydrolase inhibition AUDA on endothelial function in hypercholesterolemic rats. Methods: Hypercholesterolemia was induced by using Matos diet for 8 weeks and it significantly increased TC, TG, and LDL-C and decreased HDL-C. AUDA, was used with a dose of 0.35 mg/ kg for 10 weeks via gastric gavage every other day. Results: AUDA treated group has significantly lower total-C, TG, LDL-C and higher HDL-C as compared to untreated group. AUDA also improved vascular reactivity and vasodilatory response to different doses of Acetyl choline. Histopathological examination of aortic rings showed reduced development of atherosclerotic changes in the vascular wall with no effect on e-NOS expression in vascular endothelial cells. Conclusions: We can conclude that AUDA treatment has improved lipid profile and protect against development of atherosclerotic histopathological changes.

Multi‐therapeutic action of chronic treatment with tadalafil in cardiovascular alterations and erectile function of rats with heart failure

IntroductionHeart failure (HF) is the common endpoint of several cardiovascular diseases. HF and ED share similar pathophysiological mechanisms that contribute to the progression of both disorders, with emphasis on endothelial dysfunction and reduced nitric oxide (NO) bioavailability. Drugs mimic the effect exerted by NO, such as tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor used in the ED treatment. Therefore, tadalafil may be a multi‐therapeutic agent in the treatment of cardiovascular alterations and erectile dysfunction associated with impaired of NO‐sGC‐cGMP signaling pathway? Thus, using the aortocaval fistula model (FAC) we investigated the contribution of tadalafil chronic treatment in the cardiac, vascular and erectile dysfunction of HF rats.MethodsHF was surgically induced through the FAC model, and after 8 weeks, these animals were submitted to cardiac function evaluation (echocardiogram) and subdivided into 3 groups: Sham, HF and HF/Tadalafil (5mg/day IP for more 4 weeks). Intracavernous pressure measurement (ICP) was used to evaluate erectile function in vivo. Response concentration curves were constructed to assess both vascular reactivity in response to phenylephrine (PE), acetylcholine and sodium nitroprusside (SNP), as well as the cavernosal muscle (CC) reactivity in response to PE and SNP. Electrical stimulation (EFS) were obtained to evaluate neurogenic contraction and nitrergic relaxation in CC rat.ResultsAfter 12 weeks, HF group presented both reduced of ejection and shortening fraction (p&lt;0.05), as well present cardiac hypertrophy (P &lt;0.05) when compared to the Sham group. Treatment with tadaladil restored the ejection and shortening fraction in the HF/Tadalafil (p&lt;0.05), and reduced cardiac hypertrophy induced by HF. Moreover, HF animals presented an increase in the contractile vascular response mediated by PE when compared to Sham group (p&lt;0.05), being this vascular hypercontractility restored by the tadalafil treatment (p&lt;0.05). In addition, aorta of HF rats showed reduction of the ACh‐mediated relaxation (p&lt;0.05) compared to the control, and this effect was restored by tadalafil treatment (p&lt;0.05). Regarding erectile function, the data show that HF animals present a reduction of intracavernous pressure (p&lt;0.05) compared to the Sham group, that was restored by tadalafil treatment (p&lt;0.05). The contractile mechanism of CC, in response to PE and neurogenic electrical stimulation (p&lt;0.05) were increased in HF rats, on the other side, the treatment with tadalafil improve the CC hypercontractility in these animals (p&lt;0.05). In addition, tadalafil treatment also restored both SNP (p&lt;0.05) and nitrergic (p&lt;0.05) mediated relaxation in the CC of HF rats.ConclusionOur data show that the chronic treatment with tadalafil improved both vascular‐ and no‐vascular smooth muscle reactivity since exerting beneficial effects in the cardiovascular and erectile function in HF rats. Data suggesting that tadalafil acts is a multi‐therapeutic agent in HF rats.Support or Funding InformationFinancial suport: FAPESP: 2011/21095‐4 / CNPq: 423987/2016‐0This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Organ-specific changes in vascular reactivity and roles of inducible nitric oxide synthase and endothelin-1 in a rabbit endotoxic shock model.

Hemorrhagic shock-induced changes in vascular reactivity appear organ-specific. In the present study, we examined the hypothesis that vascular reactivity induced by septic shock similarly displays organ-specific differences and is regulated by inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1). Endotoxic shock was induced in rabbits by administration of lipopolysaccharide (LPS) (1 mg/kg), and organ specificity of vascular reactivity of superior mesenteric artery (SMA), celiac artery (CA), and left renal artery (LRA) as well as the potential involvement of iNOS and ET-1 examined. Vascular reactivity of SMA, CA, and LRA was increased at the early stages and decreased at the late stages after LPS administration. Superior mesenteric artery showed the greatest decrease in vascular reactivity in response to norepinephrine (NE) (34.9%) and acetylcholine (Ach; 32.3%), followed by LRA (NE, 33.7%; Ach, 30.5%) and CA (NE, 16.2%), whereas the relaxation reactivity of CA in response to Ach was increased to 159%. The mRNA and protein levels of iNOS and ET-1 in SMA, CA, and LRA were not affected at the early stages of endotoxic shock after LPS administration but significantly increased at the late stages. Expression levels were higher in SMA than CA and LRA and negatively correlated with the decrease in vascular reactivity. The iNOS and ET-1 inhibitors, aminoguanidine (20 mg/kg) and PD-142893 (0.02 mg/kg), respectively, induced significant improvements in vascular reactivity and organ perfusion and stabilized the hemodynamic parameters in rabbits subjected to endotoxic shock. Changes in vascular reactivity during endotoxic shock are organ-specific. Differential expression patterns of iNOS and ET-1 in different blood vessels contribute to the organ specificity of vascular reactivity. Therapeutic study, level II.

Efeito da atividade física sobre a reatividade vascular em idosas hipertensas

Introdução: O crescimento da população idosa aumentou a incidência de doenças crônicas não transmissíveis, como por exemplo, a hipertensão arterial. Objetivo: Verificar o efeito da atividade física sobre a reatividade vascular em idosas hipertensas. Métodos: A coleta de dados foi realizada de outubro a novembro de 2016. Foi efetuado um programa de exercícios de treino de força e aeróbico realizados durante 4 semanas, com duração de 40 minutos. Após os exercícios realizou-se o Cold Pressor Test (CPT), em seguida foi aferida a pressão arterial e a frequência cardíaca imediatamente após o estímulo e aos 5, 10, 15 e 20 minutos subsequentes. Resultados: Mostraram que ambas as intervenções são efetivas para uma menor resposta de reatividade vascular das idosas, quando submetidas ao estresse. Conclusão: Conclui-se que as intervenções são efetivas como um tratamento não farmacológico para a hipertensão arterial, além de promover uma diminuição significativa da pressão arterial pós CPT.

Influence of fitness and age on the endothelial response to acute inflammation.

What is the central question of the study? What are the effects of age and fitness on the vascular response to acute inflammation in younger and older adults? What is the main finding and its importance? In older adults, cardiorespiratory fitness level has a differential impact on endothelial function after acute inflammation. Compared with older adults with low fitness, older, moderately fit adults have a greater decrease in endothelial function, similar to that of younger adults. These findings have important implications in support of the beneficial effects of higher cardiorespiratory fitness in maintaining vascular reactivity and the ability to respond to stressors. Inflammation is associated with greater risk of cardiovascular events and reduced vascular function with ageing. Higher cardiorespiratory fitness is associated with lower risk of cardiovascular events and better vascular function. We evaluated the role of fitness in the vascular response to acute inflammation in 26 younger adults (YA) and 62 older adults (OA). We used an influenza vaccine to induce acute inflammation. Blood pressure, flow-mediated dilatation (FMD), augmentation index, carotid elastic modulus and inflammatory markers were measured before and 24h after vaccination. Peak oxygen uptake was measured via a treadmill test. 'Fit' was defined as a peak oxygen uptake greater than the age- and sex-determined 50th percentile according to the American College of Sports Medicine. An interaction effect existed for the FMD response during acute inflammation (P<0.05). The YA (low fit, from 11.5±1.8 to 9.2±1.3%; moderately fit, from 11.9±0.8 to 9.0±0.8%) and moderately fit OA (from 7.5±1.0 to 3.9±0.8%) had similar reductions in FMD at 24h (P<0.05). Low-fit OA did not reduce FMD at 24h (from 5.5±0.4 to 5.2±0.5%, P>0.05). The reduction in FMD in YA was similar between fitness groups (P>0.05). All groups had similar reductions in mean arterial pressure and increases in inflammatory markers. The augmentation index and carotid elastic modulus did not change during acute inflammation. In conclusion, in OA, higher fitness is associated with a greater decrease in endothelial function during acute inflammation, and this response is similar to that of young adults. This suggests that moderately fit OA may maintain vascular reactivity in response to stress, indicating preserved vascular function in moderately fit versus low-fit OA.