scholarly journals sGC Activity and Regulation of Blood Flow in a Zebrafish Model System

2021 ◽  
Vol 12 ◽  
Author(s):  
Krishan K. Vishnolia ◽  
Aleksandar Rakovic ◽  
Celine Hoene ◽  
Karim Tarhbalouti ◽  
Zouhair Aherrahrou ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Model System ◽  
Linear Velocity ◽  
Chromosomal Locus ◽  
Zebrafish Model ◽  
Flow Parameters ◽  
Screening Experiments ◽  
Significant Difference ◽  
Underlying Mechanisms

Soluble guanylyl cyclase (sGC) protein is a heterodimer formed by two subunits encoded by GUCY1A1 and GUCY1B1 genes. The chromosomal locus 4q32.1 harbors both of these genes, which has been previously significantly associated with coronary artery disease, myocardial infarction, and high blood pressure. Blood pressure is influenced by both the environment and genetics and is complemented by several biological pathways. The underlying mechanisms associated with this locus and its genes still need to be investigated. In the current study, we aimed to establish the zebrafish as a model organism to investigate the mechanisms surrounding sGC activity and blood pressure. A zebrafish mutant gucy1a1 line was generated using the CRISPR-Cas9 system by inducing a 4-bp deletion frameshift mutation. This mutation resulted in a reduction of gucy1a1 expression in both heterozygote and homozygote zebrafish. Blood flow parameters (blood flow, arterial pulse, linear velocity, and vessel diameter) investigated in the gucy1a1 mutants showed a significant increase in blood flow and linear velocity, which was augmented in the homozygotes. No significant differences were observed for the blood flow parameters measured from larvae with individual morpholino downregulation of gucy1a1 and gucy1b1, but an increase in blood flow and linear velocity was observed after co-morpholino downregulation of both genes. In addition, the pharmacological sGC stimulator BAY41-2272 rescued the impaired cGMP production in the zebrafish gucy1a1± mutant larvae. Downregulation of cct7 gene did not show any significant difference on the blood flow parameters in both wild-type and gucy1a1± background larvae. In summary, we successfully established a zebrafish platform for investigating sGC-associated pathways and underlying mechanisms in depth. This model system will have further applications, including for potential drug screening experiments.

The Haemodynamic Effects of Metabolic Acidosis in the Rat

1976 ◽  
Vol 50 (3) ◽  
pp. 177-184 ◽  
Author(s):  
J. Yudkin ◽  
R. D. Cohen ◽  
Barbara Slack
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Cardiac Output ◽  
Metabolic Acidosis ◽  
Renal Blood Flow ◽  
Hepatic Blood Flow ◽  
Conscious Rats ◽  
Blood Ph ◽  
Significant Difference

1. The effect of metabolic acidosis of 4–6 h duration on cardiac output, blood pressure, heart rate, and hepatic and renal blood flow has been studied in the rat. 2. In anaesthetized rats, blood pressure and heart rate fell linearly with blood pH in both sham-operated and nephrectomized rats. There was no significant difference between the two groups in the effect of acidosis on either variable. 3. Cardiac output showed a significant fall with increasing acidosis in the conscious rat. 4. Estimated hepatic blood flow in conscious rats showed a significant positive correlation with blood pH in both sham-operated and nephrectomized animals. There was no significant difference in estimated hepatic blood flow between the two groups of animals at any blood pH. 5. In conscious rats, increasing acidosis caused a progressive decrease in estimated renal blood flow. 6. It is concluded that the increase in the previously described apparent renal contribution to lactate removal in the acidotic rat cannot be explained by any circulatory effect mediated by the kidney. The possible relevance of the findings to lactate homeostasis is discussed.

Role of the hypothalamic PVN in the reflex reduction in mesenteric blood flow elicited by hyperthermia

2008 ◽  
Vol 295 (6) ◽  
pp. R1874-R1881 ◽  
Author(s):  
Feng Chen ◽  
Melissa Dworak ◽  
Yuliang Wang ◽  
Joo Lee Cham ◽  
Emilio Badoer
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Body Temperature ◽  
Core Body Temperature ◽  
Separate Group ◽  
Control Group ◽  
Mesenteric Blood Flow ◽  
Significant Difference ◽  
Core Body

The hypothalamic paraventricular nucleus (PVN) is an important integrative center in the brain. In the present study, we investigated whether the PVN is a key region in the mesenteric vasoconstriction that normally accompanies an increase in core body temperature. Anesthetized rats were monitored for blood pressure, heart rate, mesenteric blood flow, and vascular conductance. In control rats, elevation of core body temperature to 41°C had no significant effect on blood pressure, increased heart rate, and reduced mesenteric blood flow by 21%. In a separate group of rats, muscimol was microinjected bilaterally (1 nmol/side) into the PVN. Compared with the control group, there was no significant difference in the blood pressure and heart rate responses elicited by the increase in core body temperature. In contrast to control animals, however, mesenteric blood flow did not fall in the muscimol-treated rats in response to the elevation in core body temperature. In a separate group, in which muscimol was microinjected into regions outside the PVN, elevating core body temperature elicited the normal reduction in mesenteric blood flow. The results suggest that the PVN may play a key role in the reflex decrease in mesenteric blood flow elicited by hyperthermia.

scholarly journals Retinal Nerve Fibre Layer and Ophthalmic Artery Blood Parameters in Pseudoexfoliation Syndrome and Pseudoexfoliative Glaucoma

2021 ◽  
Author(s):  
Hacı Koç ◽  
Faruk Kaya ◽  
Ümit İpeksoy
Keyword(s):  
Blood Flow ◽  
Negative Correlation ◽  
Ophthalmic Artery ◽  
Significant Negative Correlation ◽  
Doppler Imaging ◽  
Control Group ◽  
Artery Blood Flow ◽  
Pseudoexfoliative Glaucoma ◽  
Flow Parameters ◽  
Significant Difference

Abstract PurposeThis study investigates the relationship between ophthalmic artery blood flow parameters and retinal nerve fiber layer (RNFL) thickness in eyes with pseudoexfoliation. MethodsThree comparisons were made in this study. In the first, eyes without glaucoma with pseudoexfoliation in any of the eyes were compared with the control group. In the second, eyes with pseudoexfoliation and without glaucoma were compared with those with pseudoexfoliation and glaucoma. In the third, cases with glaucoma and pseudoexfoliation were compared with the control group. Ophthalmic artery colour Doppler imaging measurements were performed in all patients. Also, peripapillary RNFL analysis was performed. ResultsA statistically significant difference was found between the total RNFL measurements according to group (p = 0.012; p < 0.05). From the paired comparisons, the total RNFL measurements from the control group were higher than the group without glaucoma (p = 0.010). No statistically significant difference was found between the total RNFL measurements of the other groups (p > 0.05). In the pseudoexfoliative glaucoma (PXG) group, there was a statistically significant negative correlation between total RNLF and Peak systolic velocity (PSV) (r = -0.743; p < 0.01). There was also a statistically significant negative correlation between total RNLF and End diastolic velocity (EDV) (r = -0.691; p < 0.01). There was no significant relationship between total RNLF and resistive index (RI) measurements (p > 0.05). ConclusionPseudoexfoliation syndrome(PXS) caused a decrease in the PSV and EDV values of ophthalmic artery blood flow parameters. Again, PXS caused a decrease in total RNFL, RNFL S, RNFL I and RNFL T thickness values.

Flow-mediated dilation analysis coupled with nitric oxide transport to enhance the assessment of endothelial function

2021 ◽  
Author(s):  
Tianxiang Ma ◽  
Xiao Liu ◽  
Quan Ren ◽  
Zhexi Zhang ◽  
Xiaoning Sun ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Flow ◽  
Endothelial Function ◽  
Characteristic Parameter ◽  
Flow Mediated Dilation ◽  
Fractional Flow ◽  
Arterial Diameter ◽  
Brachial Artery Diameter ◽  
Significant Difference

Flow-mediated dilation (FMD), mainly mediated by nitric oxide (NO), aims to assess the shear-induced endothelial function, which is widely quantified by the relative change in arterial diameter after dilation (FMD%). However, FMD% is affected by individual differences in blood pressure, blood flow and arterial diameter. To reduce these differences and enhance the assessment of FMD to endothelial function, we continuously measured not only the brachial artery diameter and blood flow with ultrasound but also blood pressure with non-invasive monitor during standard FMD test. We further constructed an analytical model of FMD coupled with NO transport, blood flow, and arterial deformation. Combining the time-averaged and peak values of arterial diameter, blood flow and pressure, and the modeling, we assumed the artery was completely healthy and calculated an ideally expected FMD% (eFMD%). Then, we expressed the fractional flow-mediated dilation (FFMD%) for the ratio of measured FMD% (mFMD%) to eFMD%. Furthermore, using the continuous waveforms of arterial diameter, blood flow and pressure, the endothelial characteristic parameter (ϵ) was calculated, which describes the function of the endothelium to produce NO and ranges from 1 to 0 representing the endothelial function from healthiness to complete loss. We found that the mFMD% and eFMD% between the young age (n=5, 21.2±1.8yr) and middle age group (n=5, 34.0±2.1yr) have no significant difference (P=0.222, P=0.385). In contrast, the FFMD% (P=0.008) and ϵ (P=0.007) both show significant differences. Therefore, the fractional flow-mediated dilation (FFMD%) and the endothelial characteristic parameter (ϵ) may have the potential for specifically diagnosing the endothelial function.

scholarly journals Microcirculation Disorders in Patients with Severe COVID-19

2021 ◽  
Vol 18 (4) ◽  
pp. 7-19
Author(s):  
E. E. Ladozhskaya-Gapeenko ◽  
K. N. Khrapov ◽  
Yu. S. Polushin ◽  
I. V. Shlyk ◽  
N. N. Petrishchev ◽  
...  
Keyword(s):  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Capillary Blood ◽  
Linear Velocity ◽  
Capillary Blood Flow ◽  
Control Group ◽  
Doppler Flowmetry ◽  
Occlusion Test ◽  
Cuff Deflation ◽  
Significant Difference

Impaired microcirculation due  to endothelial dysfunction in COVID-19  is considered  to be  the most important link in the pathogenesis of this disease. However, due  to  the  complexity of its  instrumental  assessment  in critically ill patients,  the data available  in  the  literature on specific manifestations of endothelial dysfunction are very contradictory.The objective:  to determine  the most characteristic capillaroscopic signs of microvascular disorders and  to assess  the  state of microcirculation regulation in patients with severe COVID-19.Subjects  and Methods. When admitted  to  the  intensive  care unit,  60 patients with  COVID-19  and  12  patients with chronic cardiovascular pathology without COVID-19 (Comparison Group) were examined. All patients underwent microscopy of the microcirculatory bed of finger nail bed; the following parameters were assessed: diameters of the venous, arterial and transitional parts of capillaries, height of capillary loops, density of capillaries per  1 mm of the  length of the perivascular zone,  the average  linear velocity of capillary blood  flow (LVCBF), and  thickness of the perivascular zone. The presence of avascular zones,  the number of capillaries in the visualized field with circulating aggregates in the lumen, and the shape of capillaries were taken into account.  In addition, an occlusion test using laser Doppler flowmetry was performed  in 32 patients with COVID-19. The maximum post-occlusive increase in blood flow at the moment of cuff deflation was assessed, as well as changes in the mean value of post-occlusive blood flow relative to the baseline within 3 minutes after cuff deflation.Results.  In 53 (88.3%) patients with COVID-19, abnormalities corresponding to chronic microcirculatory changes in the form of predominance of pathological capillary forms were detected. Microaggregates in the lumen of capillaries and decreased linear velocity of blood flow were revealed in 100% of cases. When comparing groups of patients with different outcomes, statistically significant differences were revealed between the LVCBF parameters (in the survivors -  354.35 ± 44.78 pm/sec, in the deceased - 278.4 ± 26.59 pm/sec), as well as between the values of the perivascular zones thickness  (95.35  ±  15.96 microns versus  159.93 ±  19.90 microns). The results of the post-occlusion  test revealed  a significant difference between the groups in terms of the maximum post-occlusion gain (39.42 ± 3.85 BPU in the group with a favorable outcome, 27.69 ± 3.19 BPU in the group with an unfavorable outcome, 47.23 ±  1.78 BPU in the control group). In both groups, there was no increase in this parameter relative to the initial blood flow. At the same time, in the control group, the average index of post-occlusive blood flow was higher than the initial level.Conclusions. Acute microcirculation disorders with decreased linear velocity of capillary blood flow, circulation of aggregates, increased thickness of the perivascular zone were detected in all patients with severe COVID-19 but especially in those with unfavorable outcomes. Vascular tone regulation disorders were manifested by the absence of reactive hyperemia in response to acute ischemia, as well as a decrease in maximal flow-induced increase. These changes fit into the concept of endothelial dysfunction. Signs of chronic microcirculation disorders in most patients increase the risk of severe COVID-19.

scholarly journals Random squat/stand maneuvers: a novel approach for assessment of dynamic cerebral autoregulation?

2017 ◽  
Vol 123 (3) ◽  
pp. 558-566 ◽  
Author(s):  
Sam C. Barnes ◽  
Naomi Ball ◽  
Ronney B. Panerai ◽  
Thompson G. Robinson ◽  
Victoria J. Haunton
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Flow Velocity ◽  
Blood Flow Velocity ◽  
Cerebral Autoregulation ◽  
Arterial Blood ◽  
Transfer Function Analysis ◽  
Significant Difference ◽  
Random Frequency ◽  
Dynamic Cerebral Autoregulation

Squat/stand maneuvers (SSM) have been used to assess dynamic cerebral autoregulation (dCA), but always at a fixed frequency (FF). This study aimed to assess the use of random-frequency (RF) SSMs as a stimulus for measuring dCA and determine the reproducibility of FF and RFSSMs. Twenty-nine healthy volunteers [19 male, mean age 23.0 (4.9) yr] completed the study; 11 returned for a repeat visit (median 45 days). Heart rate, beat-to-beat blood pressure, middle cerebral artery (MCA) blood flow velocity, end-tidal CO2, and angle of the squat movement were measured. Subjects underwent four recordings: 5 min sitting, 5 min standing, FFSSMs (0.05Hz), and RFSSMs. Subjects were asked to rate the degree of exertion experienced while performing these maneuvers. Twenty-nine subjects completed the protocol; nine data sets were deemed unsuitable for further analysis. Mean ARI of 6.21 (1.04) while standing was significantly greater than during the SSMs ( P < 0.01), with mean (SD) ARI during the FF and RFSSMs being 5.16 (1.43) and 5.37 (1.21), respectively. However, no significant difference was found between the ARI estimates from the two SSMs ( P = 0.856) or for each of the four recordings between the two visits ( P = 0.645). RFSSMs were found to be significantly less tiring than FFSSMs ( P < 0.01). In conclusion, RFSSMs are an effective and noninvasive method of assessing dCA. There is no difference in the ARI estimates in comparison with FFSSMs. Although FFSSMs have been well tolerated previously, RFSSMs are preferred by healthy subjects and thus may be better tolerated by a patient population in a clinical setting. NEW & NOTEWORTHY RFSSMs provided comparable estimates of autoregulatory indices to FFSSMs. Instead of point estimates at the driven frequency, RFSSMs generate a broader power spectrum of changes in arterial blood pressure and cerebral blood flow velocity, allowing direct comparison with spontaneous fluctuations through transfer function analysis. Moreover, random-frequency SSMs are preferred by participants. They are a novel tool by which larger blood pressure oscillations can be elicited for the reliable measurement of dynamic cerebral autoregulation.

Abstract 631: Maternal Separation (msep) Alters Baroreflex Function And Renal Blood Flow Responsiveness

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Analia S Loria
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Renal Blood Flow ◽  
Maternal Separation ◽  
Male Rats ◽  
Compensatory Mechanism ◽  
Dependent Manner ◽  
Baroreflex Function ◽  
Significant Difference ◽  
Renal Vascular

An impairment of the baroreflex buffering has been shown to precede the development of hypertension. Formerly, we reported that MSep, a model of behavioral stress during early life, impairs chronic blood pressure control and renal filtration capacity. Thus, the aim of this study was to study the baroreflex function and renal blood flow regulation in MSep rats. We used 3 month-old MSep male rats, anesthetized with isoflurane. Femoral vein catheter was fitted to infuse saline (3 ml/hr, baseline), PE (phenylephrine, 1 ug/ml, 9 ml/hr) or SNP (sodium nitroprusside, 0.5 ug/ml, 9 ml/hr). Femoral artery catheter was fitted to collect blood pressure and HR data (ADInstruments). In addition, a flow probe was placed in the left renal artery for renal blood flow (RBF) assessment (Transonic). After 45 minutes of baseline, PE infusion (2 min) was performed. Following 30-minute recovery period, SNP infusion (2 min) was achieved. Delta heart rate (HR)/Delta mean arterial pressure (MAP) relationship shows a significant difference in the slopes between MSep vs. control rats (-0.5 ±0.07 vs. -1.08 ±0.08, p<0.05). PE-induced decrease in RBF was attenuated in a dose dependent manner in MSep rats (max. delta RBF -4.8±0.8 ml/min) compared to controls (max. delta RBF -7±1.5 ml/min, p<0.05, respectively). Yet, renal vascular resistance (MAP/RBF) was not different between MSep and control rats along the 2-min period (slope: 0.43±0.02 vs. 0.42±0.03 mmHg/ml/min, respectively). These data suggest that MSep rats fail to increase HR in response to a vasodilatory agent and lower HR in response to vasoactive stimulus. Furthermore, attenuated alpha-adrenergic-induced renal vascular responses support the existence of a compensatory mechanism in response to an increased sympathetic outflow to the kidney, as previously suggested. The contribution of the different components of the autonomic nervous system is the focus of ongoing studies.

27 Cerebral Autoregulation Associated with Falls in Older Persons with Orthostatic Hypotension?

2019 ◽  
Vol 48 (Supplement_4) ◽  
pp. iv6-iv8
Author(s):  
Nor Izzati Saedon ◽  
Goh Choon Hian ◽  
Frith James ◽  
Wan Azman Wan Adnan ◽  
Tan Maw Pin
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Orthostatic Hypotension ◽  
Flow Velocity ◽  
Cerebral Autoregulation ◽  
Community Dwelling ◽  
Brain Blood Flow ◽  
Older Individuals ◽  
Significant Difference ◽  
Continuous Blood Pressure

Abstract Background It is considered well-established that orthostatic hypotension (OH) is associated with falls, population-based studies have found that a large proportion of community-dwelling older adults fulfill the criteria for OH without experiencing falls. It is therefore postulated that older individuals with OH may only experience fall if cerebral autoregulation, which is the mechanism by which the brain blood flow is maintained constant through a autoregulatory range, is impaired. Objective To evaluate the relationship between cerebral autoregulation and OH in older individuals with and without a history of falls. Method Individuals aged 3 60 years were recruited from medical clinics, by word of mouth, and from existing research registries. Baseline sociodemographics, detailed medical history and medication history were obtained. Bilateral middle cerebral artery (MCA) blood flow were recorded using transcranial Doppler ultrasound (TCD) synchronized with non-invasive continuous blood pressure and ECG recordings. Synchronized brain blood flow signals, heart trace and blood pressure signals were first recorded during 10 minutes’ supine rest. Participants were then be asked to perform a standard set of mathematical calculations, a Valsalva maneuver and to stand up from a seated position. Results 36 participants have been evaluated to date (13 fallers, 23 non-Fallers). There is no statistically significant difference in gender, ethnicity or height and weight between groups. Fluctuations in MCA flow velocity were observed with spontaneous fluctuations in blood pressure at rest and with induced blood pressure changes during the challenge maneuvers. Visual inspection of the signals obtained suggested that changes in MCA flow velocity were more marked among fallers and non-fallers. Conclusion Synchronization of cerebral blood flow and continuous blood pressure signals opens up numerous new possibilities in research and clinical practice. Our preliminary findings suggest that cerebral autoregulation does play a role in determining the presence of symptomats in older individuals with OH.

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