Pressure and Flow Relations in the Systemic Arterial Tree Throughout Development From Newborn to Adult.
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ABSTRACT:
SUBMITTER: Westerhof BE
PROVIDER: S-EPMC7248228 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveArterial hemodynamics and vascular calcification are associated with increased risk for cardiovascular disease, but their inter-relations remain unclear. We sought to examine the associations of arterial stiffness, pressure pulsatility, and wave reflection with arterial calcification in individuals free of prevalent cardiovascular disease.Approach and resultsFramingham Heart Study Third Generation and Offspring Cohort participants free of cardiovascular disease underwent applanation tonometry to measure arterial stiffness, pressure pulsatility, and wave reflection, including carotid-femoral pulse wave velocity, central pulse pressure, forward wave amplitude, and augmentation index. Participants in each cohort (n=1905, 45±6 years and n=1015, 65±9 years, respectively) underwent multidetector computed tomography to assess the presence and quantity of thoracic aortic calcification, abdominal aortic calcification, and coronary artery calcification. In multivariable-adjusted models, both higher carotid-femoral pulse wave velocity and central pulse pressure were associated with greater thoracic aortic calcification and abdominal aortic calcification, whereas higher augmentation index was associated with abdominal aortic calcification. Among the tonometry measures, carotid-femoral pulse wave velocity was the strongest correlate of all calcification measures in multivariable-adjusted models (odds ratio per SD for thoracic aortic calcification, 2.69 [95% confidence interval, 2.17-3.35]; abdominal aortic calcification, 1.47 [95% confidence interval, 1.26-1.73]; and coronary artery calcification, 1.48 [95% confidence interval, 1.28-1.72]; all P<0.001, respectively). We observed stronger relations of carotid-femoral pulse wave velocity, central pulse pressure, and forward wave amplitude with nearly all continuous calcification measures in the younger Third Generation Cohort as compared with the Offspring Cohort.ConclusionsIn community-dwelling individuals without prevalent cardiovascular disease, abnormal central arterial hemodynamics were positively associated with vascular calcification and were observed at younger ages than previously recognized. The mechanisms of these associations may be bidirectional and deserve further study.
| S-EPMC4199901 | biostudies-literature
Project description:We used next-generation RNA sequencing (RNA-Seq) technology on the whole transcriptome to identify genes whose expression is consistently affected by obesity across multiple arteries. Specifically, we examined transcriptional profiles of the iliac artery as well as the feed artery, first, second, and third branch order arterioles in the soleus, gastrocnemius, and diaphragm muscles from obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long-Evans Tokushima Otsuka (LETO) rats. Within the gastrocnemius and soleus muscles, the number of genes differentially expressed with obesity tended to increase with increasing branch order arteriole number (i.e., decreasing size of the artery). This trend was opposite in the diaphragm. We found a total of 15 genes that were consistently upregulated with obesity (MIS18A, CTRB1, FAM151B, FOLR2, PXMP4, OAS1B, SREBF2, KLRA17, SLC25A44, SNX10, SLFN3, MEF2BNB, IRF7, RAD23A, LGALS3BP) and five genes that were consistently downregulated with obesity (C2, GOLGA7, RIN3, PCP4, CYP2E1). A small fraction (∼9%) of the genes affected by obesity was modulated across all arteries examined. In conclusion, the present study identifies a select number of genes (i.e., 20 genes) whose expression is consistently altered throughout the arterial network in response to obesity and provides further insight into the heterogeneous vascular effects of obesity. Although there is no known direct function of the majority of 20 genes related to vascular health, the obesity-associated upregulation of SREBF2, LGALS3BP, IRF7, and FOLR2 across all arteries is suggestive of an unfavorable vascular phenotypic alteration with obesity. These data may serve as an important resource for identifying novel therapeutic targets against obesity-related vascular complications.
| S-EPMC4233283 | biostudies-literature
Project description:Key pointsThe functional roles of the capsaicin receptor, TRPV1, outside of sensory nerves are unclear. We mapped TRPV1 in the mouse circulation, revealing extensive expression in the smooth muscle of resistance arterioles supplying skeletal muscle, heart and adipose tissue. Activation of TRPV1 in vascular myocytes constricted arteries, reduced coronary flow in isolated hearts and increased systemic blood pressure. These functional effects were retained after sensory nerve ablation, indicating specific signalling by arterial TRPV1. TRPV1 mediated the vasoconstrictive and blood pressure responses to the endogenous inflammatory lipid lysophosphatidic acid. These results show that TRPV1 in arteriolar myocytes modulates regional blood flow and systemic blood pressure, and suggest that TRPV1 may be a target of vasoactive inflammatory mediators.AbstractThe capsaicin receptor, TRPV1, is a key ion channel involved in inflammatory pain signalling. Although mainly studied in sensory nerves, there are reports of TRPV1 expression in isolated segments of the vasculature, but whether the channel localizes to vascular endothelium or smooth muscle is controversial and the distribution and functional roles of TRPV1 in arteries remain unknown. We mapped functional TRPV1 expression throughout the mouse arterial circulation. Analysis of reporter mouse lines TRPV1PLAP-nlacZ and TRPV1-Cre:tdTomato combined with Ca2+ imaging revealed specific localization of TRPV1 to smooth muscle of terminal arterioles in the heart, adipose tissue and skeletal muscle. Capsaicin evoked inward currents (current density ∼10% of sensory neurons) and raised intracellular Ca2+ levels in arterial smooth muscle cells, constricted arterioles ex vivo and in vivo and increased systemic blood pressure in mice and rats. Further, capsaicin markedly and dose-dependently reduced coronary flow. Pharmacological and/or genetic disruption of TRPV1 abolished all these effects of capsaicin as well as vasoconstriction triggered by lysophosphatidic acid, a bioactive lipid generated by platelets and atherogenic plaques. Notably, ablation of sensory nerves did not affect the responses to capsaicin revealing a vascular smooth muscle-restricted signalling mechanism. Moreover, unlike in sensory nerves, TRPV1 function in arteries was resistant to activity-induced desensitization. Thus, TRPV1 activation in vascular myocytes enables a persistent depolarizing current, leading to constriction of coronary, skeletal muscle and adipose arterioles and a sustained increase in systemic blood pressure.
| S-EPMC8565923 | biostudies-literature
Project description:We developed a method for measuring in vivo venular volumes and the mean systemic filling pressure in the limbs using near-infrared spectroscopy (NIRS). We aimed to validate the NIRS methodology by comparing two independent methods of calculation based on different physiological approaches. Pressure-volumes (P-V) curves were recorded following graded venous occlusion on the forearm. Values from a P-V curves analysis model (method 1) were compared with data derived from a resistor-capacitance calculation model (method 2) based on arterial pressure and venous compliance. We tested these methods on 10 healthy participants at rest and during exercise and on 6 severely ill patients. Results from method 1 were comparable with those calculated by method 2. Venular volumes calculated using method 1 correlated linearly with those calculated using method 2 both in participants (R2 = 0.98) and in patients (R2 = 0.94). A good agreement between methods was shown with few values out of the range of ± 1.96 standard deviation. Our findings added mathematical consistency for the NIRS methodology validation in the venular P-V assessment with no flow interruption. Further research will be required to confirm the relevance of the methodology in the clinical setting.
| S-EPMC8338930 | biostudies-literature
Project description:Modifiable risk factors, such as diet, are becomingly increasingly important in the management of cardiovascular disease, one of the greatest major causes of death and disease burden. Few studies have examined the role of diet as a possible means of reducing arterial stiffness, as measured by pulse wave velocity, an independent predictor of cardiovascular events and all-cause mortality. The aim of this study was to investigate whether dairy food intake is associated with measures of arterial stiffness, including carotid-femoral pulse wave velocity and pulse pressure. A cross-sectional analysis of a subset of the Maine-Syracuse Longitudinal Study sample was performed. A linear decrease in pulse wave velocity was observed across increasing intakes of dairy food consumption (ranging from never/rarely to daily dairy food intake). The negative linear relationship between pulse wave velocity and intake of dairy food was independent of demographic variables, other cardiovascular disease risk factors, and nutrition variables. The pattern of results was very similar for pulse pressure, whereas no association between dairy food intake and lipid levels was found. Further intervention studies are needed to ascertain whether dairy food intake may be an appropriate dietary intervention for the attenuation of age-related arterial stiffening and reduction of cardiovascular disease risk.
| S-EPMC3341626 | biostudies-literature
Project description:Impaired regulation of blood pressure on standing can lead to adverse outcomes, including falls, syncope, and disorientation. Mean arterial pressure (MAP) typically increases on standing; however, an insufficient increase or a decline in MAP on standing may result in decreased cerebral perfusion. Orthostatic hypotension has been reported in older people with increased arterial stiffness, whereas the association between orthostatic change in MAP and arterial stiffness in young- to middle-aged individuals has not been examined. We analyzed orthostatic blood pressure response and comprehensive hemodynamic data in 3205 participants (1693 [53%] women) in the Framingham Heart Study Third Generation cohort. Participants were predominantly middle aged (mean age: 46±9 years). Arterial stiffness was assessed using carotid-femoral pulse wave velocity, forward pressure wave amplitude, and characteristic impedance of the aorta. Adjusting for standard cardiovascular disease risk factors, orthostatic change in MAP (6.9±7.7 mm Hg) was inversely associated with carotid-femoral pulse wave velocity (partial correlation, rp=-0.084; P<0.0001), forward wave amplitude (rp=-0.129; P<0.0001), and characteristic impedance (rp=-0.094; P<0.0001). The negative relation between forward wave amplitude and change in MAP on standing was accentuated in women (P=0.002 for sex interaction). Thus, higher aortic stiffness was associated with a blunted orthostatic increase in MAP, even in middle age. The clinical implications of these findings warrant further study.
| S-EPMC5382873 | biostudies-literature
Project description:Vascular flow through tissues is regulated via a number of homeostatic mechanisms. Localized control of tissue blood flow, or autoregulation, is a key factor in regulating tissue perfusion and oxygenation. We show here that the net balance between two hypoxia-inducible factor (HIF) transcription factor isoforms, HIF-1? and HIF-2?, is an essential mechanism regulating both local and systemic blood flow in the skin of mice. We also show that balance of HIF isoforms in keratinocyte-specific mutant mice affects thermal adaptation, exercise capacity, and systemic arterial pressure. The two primary HIF isoforms achieve these effects in opposing ways that are associated with HIF isoform regulation of nitric oxide production. We also show that a correlation exists between altered levels of HIF isoforms in the skin and the degree of idiopathic hypertension in human subjects. Thus, the balance between HIF-1? and HIF-2? expression in keratinocytes is a control element of both tissue perfusion and systemic arterial pressure, with potential implications in human hypertension.
| S-EPMC3808605 | biostudies-literature
Project description:The spatial organization of chromosomes is critical in establishing gene expression programs. We generated in situ Hi-C maps throughout zebrafish development to gain insight into higher-order chromatin organization and dynamics. Zebrafish chromosomes segregate in active and inactive chromatin (A/B compartments), which are further organized into topologically associating domains (TADs). Zebrafish A/B compartments and TADs have genomic features similar to those of their mammalian counterparts, including evolutionary conservation and enrichment of CTCF binding sites at TAD borders. At the earliest time point, when there is no zygotic transcription, the genome is highly structured. After zygotic genome activation (ZGA), the genome loses structural features, which are re-established throughout early development. Despite the absence of structural features, we see clustering of super-enhancers in the 3D genome. Our results provide insight into vertebrate genome organization and demonstrate that the developing zebrafish embryo is a powerful model system to study the dynamics of nuclear organization.
| S-EPMC6047509 | biostudies-literature
Project description:BackgroundGlomerular hyperfiltration resulting from an elevated intraglomerular pressure (Pglom) is an important cause of CKD, but there is no feasible method to directly assess Pglom in humans. We developed a model to estimate Pglom in patients from combined renal arterial pressure and flow measurements.MethodsWe performed hemodynamic measurements in 34 patients undergoing renal or cardiac angiography under baseline conditions and during hyperemia induced by intrarenal dopamine infusion (30 μg/kg). For each participant during baseline and hyperemia, we fitted an adapted three-element Windkessel model that consisted of characteristic impedance, compliance, afferent resistance, and Pglom.ResultsWe successfully analyzed data from 28 (82%) patients. Median age was 58 years (IQR, 52-65), median eGFR was 95 ml/min per 1.73 m2 (IQR, 74-100) using the CKD-EPI formula, 30% had microalbuminuria, and 32% had diabetes. The model showed a mean Pglom of 48.0 mm Hg (SD=10.1) at baseline. Under hyperemia, flow increased by 88% (95% CI, 68% to 111%). This resulted in a 165% (95% CI, 79% to 294%) increase in afferent compliance and a 13.1-mm Hg (95% CI, 10.0 to 16.3) decrease in Pglom. In multiple linear regression analysis, diabetes (coefficient, 10.1; 95% CI, 5.1 to 15.1), BMI (0.99 per kg/m2; 95% CI, 0.38 to 1.59), and renal perfusion pressure (0.42 per mm Hg; 95% CI, 0.25 to 0.59) were significantly positively associated with baseline Pglom.ConclusionsWe constructed a model on the basis of proximal renal arterial pressure and flow velocity measurements that provides an overall estimate of glomerular pressure and afferent and efferent resistance in humans. The model provides a novel research technique to evaluate the hemodynamics of CKD on the basis of direct pressure and flow measurements.Clinical trial registry name and registration numberFunctional HEmodynamics in patients with and without Renal Artery stenosis (HERA), NL40795.018.12 at the Dutch national trial registry (toetsingonline.nl).
| S-EPMC7460915 | biostudies-literature
Project description:Systemic blood pressure is determined, in part, by arterial smooth muscle cells (myocytes). Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and contribute to hypertension in vivo. We generated the first inducible, smooth muscle-specific knockout mice for a TRP channel, namely for PKD2 (TRPP1), to investigate arterial myocyte and blood pressure regulation by this protein. Using this model, we show that intravascular pressure and ?1-adrenoceptors activate PKD2 channels in arterial myocytes of different systemic organs. PKD2 channel activation in arterial myocytes leads to an inward Na+ current, membrane depolarization and vasoconstriction. Inducible, smooth muscle cell-specific PKD2 knockout lowers both physiological blood pressure and hypertension and prevents pathological arterial remodeling during hypertension. Thus, arterial myocyte PKD2 controls systemic blood pressure and targeting this TRP channel reduces high blood pressure.
| S-EPMC6281320 | biostudies-literature