Artery Vasomotor Research Articles

Effects of radial artery spasm prophylaxis on intracoronary vasomotor responses during acetylcholine spasm provocation testing

BackgroundInvasive coronary angiography via the radial approach is commonly performed following radial artery spasm prophylaxis (RASP). It is however unknown, whether RASP influences the results of coronary spasm provocation testing performed after diagnostic angiography. We aimed to investigate the effects of RASP on vasomotor responses during intracoronary acetylcholine (ACh) testing. MethodsWe retrospectively screened 372 consecutive patients (51 % female, mean age 61 ± 11 years) with angina and non-obstructive coronary arteries, who underwent intracoronary provocation with ACh according to a standardized protocol. During testing, dose-dependent clinical discomfort and concomitant ischemic electrocardiographic changes were recorded in addition to visual reductions of epicardial lumen diameters. Of these patients, 156 (42 %) received RASP (i.e. 200 μg nitroglycerin and 2.5 mg verapamil), while no RASP was administered in 216 (58 %) patients. Both groups were compared regarding age, sex, cardiovascular risk factors and ACh-test results. ResultsACh provocation testing revealed a pathological test result in 71 patients (46 %) with RASP and 103 patients (48 %) without (p = 0.752) [epicardial spasm: in 20 patients (28 %) with RASP and 42 patients (41 %) without (p = 0.120); microvascular spasm: in 51 patients (72 %) with RASP and 61 patients (59 %) without (p = 0.362)]. Overall, RASP did not significantly alter coronary artery vasomotor responses, neither regarding the frequency (p = 0.752) or type of coronary spasm (microvascular vs. epicardial; p = 0.108) nor regarding the ACh dose leading to spasm (p = 0.151). ConclusionsRASP does not significantly affect coronary vasomotor responses to ACh, suggesting that radial artery spasm prophylaxis can be routinely administered even in patients in whom intracoronary spasm testing is performed.

Cardiovascular and vasomotor pulsations in the brain and periphery during awake and NREM sleep in a multimodal fMRI study.

The cerebrospinal fluid dynamics in the human brain are driven by physiological pulsations, including cardiovascular pulses and very low-frequency (< 0.1 Hz) vasomotor waves. Ultrafast functional magnetic resonance imaging (fMRI) facilitates the simultaneous measurement of these signals from venous and arterial compartments independently with both classical venous blood oxygenation level dependent (BOLD) and faster arterial spin-phase contrast. In this study, we compared the interaction of these two pulsations in awake and sleep using fMRI and peripheral fingertip photoplethysmography in both arterial and venous signals in 10 healthy subjects (5 female). Sleep increased the power of brain cardiovascular pulsations, decreased peripheral pulsation, and desynchronized them. However, vasomotor waves increase power and synchronicity in both brain and peripheral signals during sleep. Peculiarly, lag between brain and peripheral vasomotor signals reversed in sleep within the default mode network. Finally, sleep synchronized cerebral arterial vasomotor waves with venous BOLD waves within distinct parasagittal brain tissue. These changes in power and pulsation synchrony may reflect systemic sleep-related changes in vascular control between the periphery and brain vasculature, while the increased synchrony of arterial and venous compartments may reflect increased convection of regional neurofluids in parasagittal areas in sleep.

Fabrication and characterization of PLLA/PCL/Mg‐Zn‐Y alloy composite stent

AbstractBioresorbable polymeric stents (BPS) can become a promising alternative over permanent stents, as it reduce in‐stent thrombosis, endothelial dysfunction, and thrombogenicity. Although, a few limitations like uncontrolled degradation, inadequate strength, and lack of radiopacity restrict its application. Thus, a novel bioresorbable radiopaque Mg‐Zn‐Y Alloy (BRM) of high effective atomic number (Zeff) was developed to reinforce and attenuate X‐rays in the polymers. After that, the optimized BRM microparticles were blended with radiolucent poly (L‐lactide)/poly (ε‐caprolactone) (PLLA/PCL) polymer and extruded into biaxially expanded (BAE) tubes. Further, in this work, BAE tubes of PLLA/PCL/BRM and PLLA/PCL were cut using the optimized Femtosecond laser machine (FSLM) parameters for fabricating cardiovascular stents. These stent materials were assessed to sustain the angioplasty procedure, such as radial strength, crimping, recoil, expansion process, and performance under cycling loading.Highlights A novel biodegradable radiopaque Mg‐Zn‐Y alloy was developed. Adding Mg alloy (5% wt.) in PLLA/PCL imparts X‐ray visibility. Composite stents show better compressive radial strength and flexibility. It also reveals low crimping recoil, expansion recoil, and foreshortening. Composite stents can withstand arterial vasomotion better than PLLA/PCL.

Bioresorbable Vascular Scaffolds: Should We use Them Again?

Context: An important development in the percutaneous management of coronary artery disease was the creation of the drug-eluting stent (DES). The DES reduces the high incidence of target lesion revascularization associated with balloon angioplasty and bare metal stents by overcoming vessel recoil and restenosis. Despite these advantages, DES carries a persistent risk of stent-related problems due to the permanent implantation of a foreign body and the limitation of arterial vasomotion. Similar to DES, bioresorbable vascular scaffolds (BRS) are intended to distribute drugs and offer mechanical support before completely degrading over the years. Evidence Acquisition: This study was a review article. The data were acquired from PubMed and Google Scholar. Medical Subject Headings (MeSH) terms were used when available, and only English articles were included in the review. Results: Recent studies have shown that the BRS is not inferior to modern DES clinically, although some clinical results are worrying, particularly the greater rates of scaffold thrombosis. Early studies showed that BRS was superior to DES; nevertheless, larger-scale applications and longer observations revealed serious problems with their use, such as reduced radial strength and a higher risk of thrombosis, which led to a higher rate of serious adverse cardiac events. Conclusions: The position of DES was not directly challenged by additional attention to procedural details and research on the second generation of BRS with innovative features. Bioresorbable vascular scaffolds still have an opportunity to demonstrate their supremacy in standout indicators.

Genetic background influences arterial vasomotor function in male and female mice.

The purpose of this study was to assess the influence of genetic background and sex on nitric oxide (NO)-mediated vasomotor function in arteries from different vascular territories. Vasomotor function was assessed in thoracic aorta, abdominal aorta, carotid arteries, and femoral arteries from the following mouse strains: SJL/J, DBA/2J, NZW/LacJ, and C57BL/6J. Contractile responses were assessed using the α1-adrenergic receptor agonist phenylephrine (PE, 10-9 -10-5 M). Vasorelaxation responses were assessed by examining relaxation to an endothelium-dependent vasodilator acetylcholine (ACh, 10-9 -10-5 M) and an endothelium-independent vasodilator sodium nitroprusside (SNP, 10-9 -10-5 M). To evaluate the role of NO, relaxation responses to ACh and SNP were assessed in the absence or presence of a nitric oxide synthase inhibitor (N omega-nitro-l-arginine methyl ester hydrochloride: 10-4 M). Vasomotor responses to ACh and PE varied across strains and among the arteries tested with some strains exhibiting artery-specific impairment. Results indicated some concentration-response heterogeneity in response to ACh and SNP between vessels from females and males, but no significant differences in responses to PE. Collectively, these findings indicate that vasomotor responses vary by genetic background, sex, and artery type.

Vasomotion in human arteries and their regulations based on ion channel regulations: 10 years study.

Vasomotion is the oscillation of vascular tone which gives rise to flow motion of blood into an organ. As is well known, spontaneous contractile organs such as heart, GI, and genitourinary tract produce rhythmic contraction. It imposes or removes pressure on their vessels alternatively for exchange of many substances. It was first described over 150 years ago, however the physiological mechanism and pathophysiological implications are not well understood. This study aimed to elucidate underlying mechanisms and physiological function of vasomotion in human arteries. Conventional contractile force measurement, immunohistochemistry, and Western blot analysis were employed to study human left gastric artery (HLGA) and uterine arteries (HUA). RESULTS: Circular muscle of HLGA and/or HUA produced sustained tonic contraction by high K+ (50 mM) which was blocked by 2 µM nifedipine. Stepwise stretch and high K+ produced nerve-independent spontaneous contraction (vasomotion) (around 45% of tested tissues). Vasomotion was also produced by application of BayK8644, 5-HT, prostagrandins, oxytocin. It was blocked by nifedipine (2 µM) and blockers of intracellular Ca2+ stores. Inhibitors of Ca2+ -activated Cl- channels (DIDS and/or niflumic acid) and ATP-sensitive K+ (KATP ) channels inhibited vasomotion reversibly. Metabolic inhibition by sodium cyanide (NaCN) and several neuropeptides also regulated vasomotion in KATP channel-sensitive and -insensitive manner. Finally, we identified TMEM16A Ca2+ -activated Cl- channels and subunits of KATP channels (Kir 6.1/6.2 and sulfonylurea receptor 2B [SUR2B]), and c-Kit positivity by Western blot analysis. We conclude that vasomotion is sensitive to TMEM16A Ca2+ -activated Cl- channels and metabolic changes in human gastric and uterine arteries. Vasomotion might play an important role in the regulation of microcirculation dynamics even in pacemaker-related autonomic contractile organs in humans.

Kv2.1 Channels Prevent Vasomotion and Safeguard Myogenic Reactivity in Rat Small Superior Cerebellar Arteries.

Vascular smooth muscle voltage-gated potassium (Kv) channels have been proposed to contribute to myogenic autoregulation. Surprisingly, in initial experiments, we observed that the Kv2 channel inhibitor stromatoxin induced vasomotion without affecting myogenic tone. Thus, we tested the hypothesis that Kv2 channels contribute to myogenic autoregulation by fine-tuning the myogenic response. Expression of Kv2 channel mRNA was determined using real-time PCR and 'multiplex' single-cell RT-PCR. Potassium currents were measured using the patch-clamp technique. Contractile responses of intact arteries were studied using isobaric myography. Expression of Kv2.1 but not Kv2.2 channels was detected in intact rat superior cerebellar arteries and in single smooth muscle cells. Stromatoxin, a high-affinity inhibitor of Kv2 channels, reduced smooth muscle Kv currents by 61% at saturating concentrations (EC50 36 nmol/L). Further, stromatoxin (10-100 nmol/L) induced pronounced vasomotion in 48% of the vessels studied. In vessels not exhibiting vasomotion, stromatoxin did not affect myogenic reactivity. Notably, in vessels exhibiting stromatoxin-induced vasomotion, pressure increases evoked two effects: First, they facilitated the occurrence of random vasodilations and/or vasoconstrictions, disturbing the myogenic response (24% of the vessels). Second, they modified the vasomotion by decreasing its amplitude and increasing its frequency, thereby destabilizing myogenic tone (76% of the vessels). Our study demonstrates that (i) Kv2.1 channels are the predominantly expressed Kv channels in smooth muscle cells of rat superior cerebellar arteries, and (ii) Kv2.1 channels provide a novel type of negative feedback mechanism in myogenic autoregulation by preventing vasomotion and thereby safeguarding the myogenic response.

Vitamin C Deficiency Exacerbates Dysfunction of Atherosclerotic Coronary Arteries in Guinea Pigs Fed a High-Fat Diet.

Vitamin C (vitC) deficiency has been associated with an increased risk of cardiovascular disease; while several putative mechanistic links have been proposed, functional evidence supporting a causal relationship is scarce. In this study, we investigated how vitC deficiency affects coronary artery vasomotor function and the development of coronary atherosclerotic plaques in guinea pigs subjected to chronic dyslipidemia by a high-fat diet regime. Female Hartley guinea pigs were fed either a control (low-fat diet and sufficient vitC) (N = 8) or a high-fat diet with either sufficient (N = 8) or deficient (N = 10) vitC for 32 weeks. Guinea pigs subjected to the high-fat diet developed significant atherosclerotic plaques in their coronary arteries, with no quantitative effect of vitC deficiency. In isolated coronary arteries, vasomotor responses to potassium, carbachol, nitric oxide, or bradykinin were studied in a wire myograph. Carbachol, bradykinin, and nitric oxide mediated relaxation in the coronary arteries of the control group. While vasorelaxation to carbachol and nitric oxide was preserved in the two high-fat diet groups, bradykinin-induced vasorelaxation was abolished. Interestingly, bradykinin induced a significant contraction in coronary arteries from vitC-deficient guinea pigs (p &lt; 0.05). The bradykinin-induced contraction was unaffected by L-NAME but significantly inhibited by both indomethacin and vitC, suggesting that, during vitC deficiency, increased release of arachidonic acid metabolites and vascular oxidative stress are involved in the constrictor effects mediated by bradykinin. In conclusion, the present study shows supporting evidence that poor vitC status negatively affects coronary artery function.

Altered retinal cerebral vessel oscillation frequencies in Alzheimer's disease compatible with impaired amyloid clearance

Retinal vessels are similar to cerebral vessels in their structure and function. Moderately low oscillation frequencies of around 0.1 Hz have been reported as the driving force for paravascular drainage in gray matter in mice and are known as the frequencies of lymphatic vessels in humans. We aimed to elucidate whether retinal vessel oscillations are altered in Alzheimer's disease (AD) at the stage of dementia or mild cognitive impairment (MCI). Seventeen patients with mild-to-moderate dementia due to AD (ADD); 23 patients with MCI due to AD, and 18 cognitively healthy controls (HC) were examined using Dynamic Retinal Vessel Analyzer. Oscillatory temporal changes of retinal vessel diameters were evaluated using mathematical signal analysis. Especially at moderately low frequencies around 0.1 Hz, arterial oscillations in ADD and MCI significantly prevailed over HC oscillations and correlated with disease severity. The pronounced retinal arterial vasomotion at moderately low frequencies in the ADD and MCI groups would be compatible with the view of a compensatory upregulation of paravascular drainage in AD and strengthen the amyloid clearance hypothesis.

Inhibition of sphingomyelinase attenuates diet – Induced increases in aortic stiffness

Sphingomyelinases ensure ceramide production and play an integral role in cell turnover, inward budding of vesicles and outward release of exosomes. Recent data indicate a unique role for neutral sphingomyelinase (nSMase) in the control of ceramide-dependent exosome release and inflammatory pathways. Further, while inhibition of nSMase in vascular tissue attenuates the progression of atherosclerosis, little is known regarding its role on metabolic signaling and arterial vasomotor function. Accordingly, we hypothesized that nSMase inhibition with GW4869, would attenuate Western diet (WD) - induced increases in aortic stiffness through alterations in pathways which lead to oxidative stress, inflammation and vascular remodeling. Six week-old female C57BL/6L mice were fed either a WD containing excess fat (46%) and fructose (17.5%) for 16 weeks or a standard chow diet (CD). Mice were variably treated with GW4869 (2.0 μg/g body weight, intraperitoneal injection every 48 h for 12 weeks). WD feeding increased nSMase2 expression and activation while causing aortic stiffening and impaired vasorelaxation as determined by pulse wave velocity (PWV) and wire myography, respectively. Moreover, these functional abnormalities were associated with aortic remodeling and attenuated AMP-activated protein kinase, Sirtuin 1, and endothelial nitric oxide synthase activation. GW4869 treatment prevented the WD-induced increases in nSMase activation, PWV, and impaired endothelium dependent/independent vascular relaxation. GW4869 also inhibited WD–induced aortic CD36 expression, lipid accumulation, oxidative stress, inflammatory responses, as well as aortic remodeling. These findings indicate that targeting nSMase prevents diet – induced aortic stiffening and impaired vascular relaxation by attenuating oxidative stress, inflammation and adverse vascular remodeling.

Protective Effects of Allicin on Acute Myocardial Infarction in Rats via Hydrogen Sulfide-mediated Regulation of Coronary Arterial Vasomotor Function and Myocardial Calcium Transport.

Acute myocardial infarction (AMI) is a condition with high morbidity and mortality, for which effective treatments are lacking. Allicin has been reported to exert therapeutic effects on AMI, but the underlying mechanisms of its action have not been fully elucidated. To investigate this, a rat model of AMI was generated by ligating the left anterior descending branch of the coronary artery. DL-propargylglycine (PAG), a specific hydrogen sulfide (H2S) synthetase inhibitor, was used to examine the effects of allicin on H2S production. Isolated coronary arteries and cardiomyocytes were assessed for vascular reactivity and cellular Ca2+ transport using a multiwire myography system and a cell-contraction-ion detection system, respectively. Allicin administration improved cardiac function and myocardial pathology, reduced myocardial enzyme levels, and increased H2S and H2S synthetase levels. Allicin administration resulted in concentration-dependent effects on coronary artery dilation, which were mediated by receptor-dependent Ca2+ channels, ATP-sensitive K+ channels, and sarcoplasmic reticulum (SR) Ca2+ release induced by the ryanodine receptor. Allicin administration improved Ca2+ homeostasis in cardiomyocytes by increasing cardiomyocyte contraction, Ca2+ transient amplitude, myofilament sensitivity, and SR Ca2+ content. Allicin also enhanced Ca2+ uptake via SR Ca2+-ATPase and Ca2+ removal via the Na+/Ca2+ exchanger, and it reduced SR Ca2+ leakage. Notably, the protective effects of allicin were partially attenuated by blockade of H2S production with PAG. Our findings provide novel evidence that allicin-induced production of H2S mediates coronary artery dilation and regulation of Ca2+ homeostasis in AMI. Our study presents a novel mechanistic insight into the anti-AMI effects of allicin and highlights the therapeutic potential of this compound.

Noradrenaline-induced basilar artery vasomotor response also varies in avian species (chickens and ducks)

Noradrenaline-induced basilar artery vasomotor response also varies in avian species (chickens and ducks)

Procedures to Evaluate the Role of Heparan Sulfate on the Reactivity of Resistance and Conductance Arteries Ex Vivo.

Evidence is emerging that disruption of the endothelial glycocalyx might contribute importantly to arterial dysfunction in the context of diabetes. One approach to assess the integrity of the endothelium and the vascular smooth muscle cell layer, in the absence of neural, humoral, and mechanical influences, is by measuring arterial vasomotion ex vivo. Here we describe a procedure to assess non-receptor-mediated vasoconstriction, receptor-mediated vasoconstriction, and endothelium-dependent and -independent vasodilation, in resistance and conductance arteries pressurized to 60mmHg. In addition to evaluating vasoreactivity using isobaric approaches, the same experimental set-up can be used to initiate a pressure gradient across the artery such that intraluminal, flow-mediated vasodilation can be measured. After recording endothelium-dependent vasodilation using isobaric or flow-mediated approaches, identical interventions can be completed in the presence of enzymes that cleave biologically active heparan sulfates into inactive disaccharide and oligosaccharide fragments to assess the contribution from: (a) endothelial-derived substances (e.g., nitric oxide via nitric oxide synthase inhibition); or (b) important components of the glycocalyx (e.g., removal of heparan sulfate via heparitinase III treatment). Here, we show that acute disruption of a predominant glycosaminoglycan i.e., heparan sulfate impairs intraluminal flow-mediated vasodilation in murine resistance arteries.

Geometric Features of the Pial Arteriolar Networks in Spontaneous Hypertensive Rats: A Crucial Aspect Underlying the Blood Flow Regulation.

BackgroundSeveral studies indicate that hypertension causes major changes in the structure of the vessel wall by affecting the regulation of blood supply to the tissues. Recently, it has been observed that capillary blood flow is also considerably influenced by the structural arrangement of the microvascular networks that undergo rarefaction (reduction of the perfused vessel number). Therefore, this study aimed to assess the geometric arrangements of the pial arteriolar networks and the arteriolar rhythmic diameter changes in spontaneously hypertensive rats (SHRs).MethodsFluorescence microscopy was utilized to observe in vivo the pial microcirculation through a closed cranial window. Pial arterioles were classified according to Strahler’s method. The arteriolar rhythmic diameter changes were evaluated by a generalization short-time Fourier transform.ResultYoung SHRs showed four orders of vessels while the adult ones only three orders. The diameter, length, and branching number obeyed Horton’s law; therefore, the vessels were distributed in a fractal manner. Larger arterioles showed more asymmetrical branches than did the smaller ones in young SHRs, while in adult SHRs smaller vessels presented asymmetrical branchings. In adult SHRs, there was a significant reduction in the cross-sectional area compared with the young SHRs: this implies an increase in peripheral resistance. Young and adult age-matched normotensive rats did not show significant alterations in the geometric arteriolar arrangement with advancing age, both had four orders of arteriolar vessels, and the peripheral resistance did not change significantly. Conversely, the frequency components evaluated in arteriolar rhythmic diameter changes of young and adult SHRs showed significant differences because of a reduction in the frequency components related to endothelial activity detected in adult SHRs.ConclusionIn conclusion, hypertension progressively causes changes in the microarchitecture of the arteriolar networks with a smaller number of vessels and consequent reduced conductivity, characteristic of rarefaction. This was accompanied by a reduction in the formation and release of independent and dependent – endothelial nitric oxide components regulating arterial vasomotion.

Hypoxic Conditions Promote Rhythmic Contractile Oscillations Mediated by Voltage-Gated Sodium Channels Activation in Human Arteries.

Arterial smooth muscle exhibits rhythmic oscillatory contractions called vasomotion and believed to be a protective mechanism against tissue hypoperfusion or hypoxia. Oscillations of vascular tone depend on voltage and follow oscillations of the membrane potential. Voltage-gated sodium channels (Nav), responsible for the initiation and propagation of action potentials in excitable cells, have also been evidenced both in animal and human vascular smooth muscle cells (SMCs). For example, they contribute to arterial contraction in rats, but their physiopathological relevance has not been established in human vessels. In the present study, we investigated the functional role of Nav in the human artery. Experiments were performed on human uterine arteries obtained after hysterectomy and on SMCs dissociated from these arteries. In SMCs, we recorded a tetrodotoxin (TTX)-sensitive and fast inactivating voltage-dependent INa current. Various Nav genes, encoding α-subunit isoforms sensitive (Nav 1.2; 1.3; 1.7) and resistant (Nav 1.5) to TTX, were detected both in arterial tissue and in SMCs. Nav channels immunostaining showed uniform distribution in SMCs and endothelial cells. On arterial tissue, we recorded variations of isometric tension, ex vivo, in response to various agonists and antagonists. In arterial rings placed under hypoxic conditions, the depolarizing agent KCl and veratridine, a specific Nav channels agonist, both induced a sustained contraction overlaid with rhythmic oscillations of tension. After suppression of sympathetic control either by blocking the release of catecholamine or by antagonizing the target adrenergic response, rhythmic activity persisted while the sustained contraction was abolished. This rhythmic activity of the arteries was suppressed by TTX but, in contrast, only attenuated by antagonists of calcium channels, Na+/Ca2+ exchanger, Na+/K+-ATPase and the cardiac Nav channel. These results highlight the role of Nav as a novel key element in the vasomotion of human arteries. Hypoxia promotes activation of Nav channels involved in the initiation of rhythmic oscillatory contractile activity.

Dipyridamole Potentiates the Endothelium-Dependent and -Independent Vasomotion in Isolated Human Small Arteries.

BACKGROUND: To investigate the effects of dipyridamole, a drug with phosphodiesterase-, adenosine reuptake-inhibiting, and prostacyclin-stimulating activity on the biological actions of nitric oxide, 30 norepinephrine-precontracted subcutaneous arterioles were prepared from specimens removed during surgery. METHODS AND RESULTS: Specimens were mounted on a myograph and relaxes through either acetylcholine, a muscarinic agonist that stimulates endothelial nitric oxide production, or sodium nitroprusside, an endothelium-independent vasodilator. Studies were performed under control conditions and after dipyridamole which potentiated in a concentration-dependent manner the vasorelaxation induced both by acetylcholine and sodium nitroprusside, indicating an endothelium-independent mechanism of action. The contribution of nitric oxide to the relaxation produced by acetylcholine was confirmed by N-monomethyl-L-arginine, a nitric oxide synthase inhibitor. In contrast, indomethacin, a cyclo-oxygenase inhibitor, was ineffective, indicating that prostacyclin stimulation could not explain the effect of dipyridamole. CGS 21680 C, an A(2)-selective adenosine receptor agonist insensitive to tissue deaminase, did not influence the relaxations induced by acetylcholine, suggesting that interference with adenosine metabolism was not implicated in the potentiating action of dipyridamole. CONCLUSIONS: Dipyridamole potentiated the vasorelaxing effect of acetylcholine and sodium nitroprusside in human subcutaneous arterioles; neither prostacyclin stimulation nor A(2) adenosine receptor stimulation could explain this effect. The data are consistent with an increase in intracellular cyclic 3' 5'-guanosine monophosphate levels secondary to the phosphodiesterase-inhibiting properties of the drug.

Hesperetin improves diabetic coronary arterial vasomotor responsiveness by upregulating myocyte voltage-gated K+ channels.

Hesperetin (HSP) is a naturally occurring flavonoid. The present study aimed to investigate the potential vasomotor effects and mechanisms of HSP action on rat coronary arteries (RCAs) injured by diabetes or high glucose concentrations. HSP (100 mg/kg/day) was intragastrically administered to the rats for 8 weeks, which were rendered diabetic with a single intraperitoneal injection of 60 mg/kg streptozotocin (STZ). The vascular tone of RCAs was recorded using a wire myograph. The voltage-dependent K+ (Kv) currents were examined using patch clamping. The expression of Kv channels (Kv1.2 and Kv1.5) was examined by western blot analysis and reverse transcription-quantitative PCR (RT-qPCR). Diabetes induced contractile hypersensitivity and vasodilator hyposensitivity in RCAs, both of which were attenuated by the chronic administration of HSP. Patch clamp data revealed that chronic HSP treatment reduced diabetes-induced suppression of Kv currents in the myocytes. Western blot and RT-qPCR analyses revealed that chronic HSP administration increased the expression of Kv1.2, but not Kv1.5, in the RCAs of diabetic rats compared with those from non-diabetic rats. In vitro analysis showed that co-incubation with HSP ameliorated high-glucose-induced suppression of Kv currents and Kv 1.2 protein expression in the myocytes. Taken together, the present study demonstrated that HSP alleviated RCA vasomotor dysfunction as a result of diabetes in rats by upregulating the expression of myocyte Kv channels.

Low Birth Weight Pigs Exhibit Altered Cerebral Hemodynamics and Vasomotor Control

Low birth weight (LBW) offspring have a higher prevalence of long‐term cognitive impairments, possibly the result of altered blood flow control in the brain. Using a pig model, we tested the hypothesis that LBW progeny exhibit abnormal cerebral hemodynamics and vasomotor control during early developmental stages of growth. At birth, littermate pigs were identified as normal (NBW=1.7±0.1 kg) or low birth weight (LBW=1.2±0.2 kg). Measurements were obtained at 28 d (weaning) and 56 d of age (n=8/group, 4M/4F per group) : i) 28‐d old NBW (28‐NBW; body mass=10.0±0.4 kg); ii) 28‐d old LBW (28‐LBW; body mass=8.0±0.4 kg); iii) 56‐d old NBW (56‐NBW; body mass=23.0±1.0 kg); and iv) 56‐d old LBW (56‐LBW; body mass=17.0±0.8 kg). Cerebral blood flow velocity was measured using Transcranial Doppler ultrasound. Thereafter, pigs were euthanatized, their brains were harvested, weighed and their pial arteries were dissected for pressure myography experiments. Briefly, pial artery vasomotor control was studied in response to a Ca2+‐activated potassium (BK) channel α‐subunit agonist NS1619 (elicits vasodilation; 1e‐10‐1e‐4 M) and sympathetic co‐transmitter neuropeptide Y (NPY; potent vasoconstrictor; 1e‐10‐1e‐4 M). Brain mass and body mass were significantly lower in LBW vs. NBW pigs (p&lt;0.01). Mean cerebral blood flow velocities were similar between LBW and NBW pigs (p≥0.20). Peak systolic velocities were greater (main effect of BW, p&lt;0.01) and reductions in end diastolic velocities approached significance in LBW vs. NBW pigs (main effect of BW, p=0.08). Accordingly, the resistive index was greater in LBW vs. NBW pigs (main effect of BW, p&lt;0.01). The maximum vasodilator response to NS1619 was not significantly different between LBW and NBW pigs (p=0.12). However, the overall magnitude of dilation (area under the curve) was lower in LBW vs. NBW pigs (main effect of BW, p&lt;0.05). The maximum vasoconstrictor response to NPY was greater in LBW vs. NBW groups (main effect of BW, p&lt;0.05). Similarly, the overall magnitude of constriction was greater in LBW vs. NBW pigs (main effect of BW, p&lt;0.01). With respect to cerebral hemodynamics and vasomotor control, no main effects of age were observed (p≥0.50). Results from this study show that LBW pigs display alterations in cerebral hemodynamics as well as cerebral vasomotor control that persist for at least 56 days. Impaired BK channel function and enhanced vasoreactivity to sympathetic co‐transmitter NPY may underlie altered cerebrovascular hemodynamics in LBW pigs.Support or Funding InformationSHRF Establishment grant (#4522) and NSERC

Implementation of home-based health promotion program to improve flow-mediated dilation among patients with subacute stroke.

INTRODUCTION:Stroke causes physiologic functional changes such as vascular resistance and arterial remodeling. This study aimed to explore the effects of 3-month regular home-based exercise rehabilitation on brachial flow-mediated dilation (FMD), daily physical activity, and upper and lower extremity sensorimotor of the acute ischemic stroke patients.MATERIALS AND METHODS:This randomized control trial was done from August 2017 to September 2018. Patients with unilateral ischemic stroke were recruited from inpatient wards at an educational hospital. Patients were randomly assigned to the home-based rehabilitation program (intervention group) or usual care (control group). Fugl-Meyer upper and lower extremity sensorimotor score and Barthel score were evaluated in both the groups before and 3 months after baseline assessment. Furthermore, brachial artery vasomotor reactivity (FMD) hemiparetic arm assessed vascular health. The intervention group received home-based rehabilitation exercise program for 3 months. The control group did not receive home-based rehabilitation program and incentive telephone call. All data were collected and analyzed by SPSS software (version 20) and appropriate statistical tests.RESULTS:Forty ischemic stroke patients (twenty in the intervention group and twenty in the control group) were examined. Results showed that Barthel score and Fugl-Meyer upper and lower extremity score and FMD in the intervention group were significantly higher than the control group after 3-month home-based exercise rehabilitation (P < 0/001).CONCLUSION:Twelve-week regular home-based exercise training was well tolerated by the intervention group. After this period, improvements were reported in brachial FMD as well as daily physical activity and upper and lower extremity functional capacity.

Role of Blood Pressure in Mediating Carotid Artery Dilation in Response to Sympathetic Stimulation in Healthy, Middle-Aged Individuals.

Carotid artery diameter responses to sympathetic stimulation, i.e., carotid artery reactivity (CAR), represent a novel test of vascular health and relates to cardiovascular disease (CVD)/risk. This study aims to understand the relationship between the increase in blood pressure and carotid artery diameter response during the CAR-test in healthy, middle-aged men. Sample consisted of 40 normotensive men (aged 31-59 years) with no history of CVD of currently taking medication. Noninvasive ultrasound was used to measure carotid artery diameter during the cold pressor test (CPT), with CAR% being calculated as the relative change from baseline (%). Mean arterial pressure (MAP) was measured with beat-to-beat blood pressure recording. CAR% was 4.4 ± 5.4%, peaking at 92 ± 43 seconds. MAP increased from 88 ± 9 mmHg to 110 ± 15 mmHg, peaked at 112 ± 38 seconds, which was significantly later than the diameter peak (P = 0.04). The correlation between resting MAP and CAR% was weak (r = 0.209 P = 0.197). Tertiles based on resting MAP or MAP-increase revealed no significant differences between groups in subject characteristics including age, body mass index, or CAR% (all P > 0.05). Subgroup analysis of individuals with carotid constriction (n = 6) vs. dilation (n = 34), revealed no significant difference in resting MAP or increase in MAP (P = 0.209 and 0.272, respectively). Our data suggest that the characteristic increase in MAP during the CPT does not mediate carotid artery vasomotion.