Buxu Tongyu Granule Alleviates Myocardial Ischemia by Activating Vascular Smooth Muscle Cell Soluble Guanylate Cyclase to Inhibit Abnormal Vasomotion

Myocardial ischemia is a serious threat to human health,and vascular dysfunction is its main cause.Buxu Tongyu(BXTY)Granule is an effective traditional Chinese medicine(TCM)for treating myocardial ischemia.However,the underlying mechanism of BXTY is still unclear.In this study,we demonstrate that BXTY ameliorates myocardial ischemia by activating the soluble guanylate cyclase(sGC)-30,50-cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG)signaling pathway in vascular smooth muscle cells(VSMCs)to dilate the arteries.BXTY was given by gavage for ten consecutive days before establishing an animal model of acute myocardial ischemia in mice via the intraperitoneal injection of pituitrin.The results showed that BXTY alleviated the symptoms of myocardial ischemia induced by pituitrin in mice,including electrocardiogram abnormalities and changes in plasma enzymes.In addition,BXTY dilated pre-constricted blood vessels and inhibited the vasoconstriction of the superior mesenteric artery in a dose-dependent but endothelial-independent manner.These effects were eliminated by preincubating vascular rings with the sGC inhibitors NS 2028 or ODQ,or with the PKG inhibitor KT 5823.Moreover,BXTY increased the protein expression of sGC-b1 and the intracellular second messenger cGMP level in mouse aortic vascular smooth muscle cells(MOVAs).NS 2028 or ODQ reversed these effects of BXTY.The expression level of the cGMP downstream effector protein PKG-1 increased after treating MOVAs with BXTY.NS 2028,ODQ,or KT 5823 also reversed this effect of BXTY.In conclusion,BXTY can improve the symptoms of acute myocardial ischemia in mice,and activating the sGC-cGMP-PKG pathway in VSMCs to induce vasodilation is its key pharmacodynamic mechanism.

Testicular vasomotion in different mammals

Vasomotion is a rhythmical variation in arterial blood flow present in many different organs among them the mttestis. Vasomofion is suggested to play an important role for the transvascular fluid exchange and the exchange of nutri-ents over the capillary wall as well as the formation of interstitial fluid. The present study was undertaken to elucidatewhether vasomotion is present in the testes of different species independent of their anatomical vascular topography.Blood flow in the testes of mouse, brush-tailed possum, tammar wallaby, ram and human was investigated by using alaser Doppler fiowmeter. Vasomotion was found in all the species investigated. (Asian J Androl 2000 Dec; 2: 297-30O)

Differential Effect of Calcium-Activated Potassium and Chloride Channels on Rat Basilar Artery Vasomotion

Spontaneous, rhythmical contractions, or vasomotion, can be recorded from cerebral vessels under both normal physiological and pathophysiological conditions. We investigated the cellular mechanisms underlying vasomotion in the cerebral basilar artery （BA） of Wistar rats. Pressure myograph video microscopy was used to study the changes in cerebral artery vessel diameter. The main results of this study were as follows： （1） The diameters of BA and middle cerebral artery （MCA） were 314.5±15.7 μm （n=15） and 233.3±10.1 μm （n=12） at 10 mmHg working pressure （P〈0.05）, respectively. Pressure-induced vasomotion occurred in BA （22/28, 78.6%）, but not in MCA （4/31, 12.9%） from 0 to 70 mmHg working pressure. As is typical for vasomotion, the contractile phase of the response was more rapid than the relaxation phase; （2） The frequency of vasomotion response and the diameter were gradually increased in BA from 0 to 70 mmHg working pressure. The amplitude of the rhythmic con- tractions was relatively constant once stable conditions were achieved. The frequency of contractions was variable and the highest value was 16.7±4.7 （n=13） per 10 min at 60 mmHg working pressure; （3） The pressure-induced vasomotion of the isolated BA was attenuated by nifedipine, NFA, 181]-GA, TEA or in Ca2＋-free medium. Nifedipine, NFA, 18^-GA or Ca2＋-free medium not only dampened vasomotion, but also kept BA in relaxation state. In contrasts, TEA kept BA in contraction state. These results sug- gest that the pressure-induced vasomotion of the isolated BA results from an interaction between Ca2＋-activated C1- channels （CaCCs） currents and Kca currents. We hypothesize that vasomotion of BA depends on the depolarizing of the vascular smooth muscle cells （VSMCs） to activate CaCCs. Depolarization in turn activates voltage-dependent Ca2＋ channels, synchronizing contractions of adjacent cells through influx of extracellular calcium and the flow of calcium through gap junctions. Subsequent calcium-induced calcium release from ryanodine-sensitive stores activates Kca channels and hyperpo- larizes VSMCs, which provides a negative feedback loop for regenerating the contractile cycle.

Effects of Ginsenoside Rb1 Babu Agent on the Amplitude of Microvascular Vasomotion

[Objectives] To study the effects of ginsenoside Rbl Babu agent on the amplitude of microvascular vasomotion. [Methods]The in vitro transdermal permeation of ginsenoside Rbl Babu agent was performed by using intelligent transdermal apparatus,and the percutaneous fluid was collected and analyzed by using high performance liquid chromatography( HPLC). The Babu agent was stuck on the skin of acupoint area,determined by Laser Doppler Flowmeter,and amplitude of microvascular vasomotion of acupoint area was recorded. [Results] With the extension of transdermal time,the cumulative permeation rate of ginsenoside Rbl increased. The amplitude of microvascular vasomotion could be significantly increased with the application of ginsenoside Rbl Babu agent( P < 0. 01). [Conclusions]The drug delivery system of ginsenoside Rbl Babu agent can release the drug into the acupoint,increase the amplitude of microvascular vasomotion,and achieve the effect of acupuncture. Therefore,ginsenoside Rbl Babu agent can replace the acupuncture clinically to treat diseases.

Impairment of the Endothelium and Disorder of Microcirculation in Humans and Animals Exposed to Infrasound due to Irregular Mechano-Transduction

The microcirculation of mammals is an autoregulated and complex synchronised system according to the current demand for nutrients and oxygen. The undisturbed course of vital functions such as of growth, blood pressure regulation, inflammatory sequence and embryogenesis is bound to endothelial integrity. The sensible vasomotion is particularly dependent on it. Mechano-transduction signalling networks play a critical role in vital cellular processes and are the decisive physiological mechanism for an adequate NO-release, main responsible for the autoregulation of vessels. Disturbed endothelial integrity, originating, e.g., from chronic oxidative stress and/or mechanic (oscillatory) stress, leads to disturbance of vasomotion as well as a disequilibrium of redox systems, recognized as main cause for the development of chronic inflammation diseases such as atherosclerosis and corresponding secondary illnesses, possibly cancer. The endothelial cytoskeleton, which corresponds to a viscoelastic “tensegrity model”, offers the possibility for mechano-transduction via its special construction. The rapidly growing knowledge about mechanical forces in cellular sensing and regulation of the last years (that culminated in the Nobel Prize award for the decoding of pressure/vibration sensing ion channels), led us to the following hypothesis: The extern stressor “Noise” produces under certain conditions an oscillatory stress field in the physiologically laminar flow bed of capillaries, which is able to lead to irregular mechano-transductions. Findings provide a strict dependence on frequency in mechano-transduction with determination of thresholds for a 1:1 transmission. The knowledge, recently gained on endothelial mechano-transduction, sheds a new light on the importance of low frequencies. This could indicate the long-sought pathophysiological way in which infrasound can exert a stressor effect at the cellular level. Noise-exposed citizens, who live near infrastructures such as a biogas installation, heat pumps, block-type thermal power stations and bigger industrial wind turbines (IWT’s), show worldwide mainly a symptomatology associated with microcirculatory disorder. Conceivable are also effects on insects or fishes, since the piezo-channels are recognised as conserved structures of all multicellular organism. An experimental design is proposed to demonstrate the direct pathological influence of infrasound of defined strength, frequency, effect/time profile and duration on the sensitive vasomotion.

Actively Circulating Volume as a Consequence of Stochasticity within Microcirculation

It is well established that in the pathology of the cardio-vascular system (CVS) only a portion of the blood volume (BV) can be in active circulation. This portion of BV is named the actively circulating volume (ACV) and is evaluated from a monotone decrease of dilution curve produced by an intravascular tracer. In given paper is presented Markov chain as a math model of the flow of a tracer throughout CVS. The consideration of CVS as a set of segments with respect to an anatomical structure and assuming the existence for CVS steady-state condition;leads to the Markov chain of the finite order with constant coefficients. The conclusions of the article are 1) there are open and closed microvessels, such that the switching from open to closed and back is a stochastic process, 2) if the switching is slow then the ACV, as the volume of heart chambers and only open for circulation vessels, can be detected.

Arsenic exposure decreases rhythmic contractions of vascular tone through sodium transporters and K^+ channels

Arsenic-contaminated drinking water is a public health problem in countries such as Taiwan, Bangladesh, United States, Mexico, Argentina, and Chile. The chronic ingestion of arsenic-contaminated drinking water increases the risk for ischemic heart disease, cerebrovascular disease, and prevalence of hypertension. Although toxic arsenic effects are controversial, there is evidence that a high concentration of arsenic may induce hypertension through increase in vascular tone and resistance. Vascular tone is regulated by the rhythmic contractions of the blood vessels, generated by calcium oscillations in the cytosol of vascular smooth muscle cells. To regulate the cytosolic calcium oscillations, the membrane oscillator model involves the participation of Ca2+ channels, calcium-activated K+ channels, Na+/Ca2+exchange, plasma membrane Ca2+-ATPase, and the Na+/K+-ATPase. However, little is known about the role of K+ uptake by sodium transporters [Na+/K+-ATPase or Na+-K+-2Cl-(NKCC1)] on the rhythmic contractions.Vascular rhythmic contractions, or vasomotion are a local mechanism to regulate vascular resistance andblood flow. Since vascular rhythmic contractions of blood vessels are involved in modulating the vascular resistance, the blood flow, and the systemic pressure,we suggest a model explaining the participation of the sodium pump and NKCC1 co-transporter in low dose arsenic exposure effects on vasomotion and vascular dysfunction.

Effect of Electro-acupuncture on Vasomotor Symptoms in Rats with Acute Cerebral Infarction Based on Phosphatidylinositol System

Objective:To investigate the effect of electro-acupuncture(EA)on vasomotor symptoms in rats with acute cerebral infarction,by observing the changes in the expression of factors related to the phosphatidylinositol(PI)system.Methods:Forty-two Wistar rats were randomly divided into 3 groups by a random number table:the control group(n=6),the model group(n=18)and the EA group(n=18).The EA group was given EA treatment at Shuigou(GV 26)instantly after modeling with middle cerebral artery occlusion(MCAO)method,while the model and control groups were not given any treatment.The degrees of neurological deficiency were evaluated using neurological severity scores(NSS)and the brain blood flow was evaluated by a laser scanning confocal microscope.Western blot analysis was conducted to detect the expression levels of G-protein subtype(Gq)and calmodulin(CaM).Competition for protein binding was conducted to detect the expression level of inositol triphosphate(IP3).Thin layer quantitative analysis was conducted to detect the expression level of diacylglycerol(DAG).The expression level of intracellular concentration of free calcium ion([Ca^(2+)]i)was detected by flow cytometry.Results:The NSS of the model group was significantly higher than the control group at 3 and 6 h after MCAO(P<0.01),while the EA group was significantly lower than the model group at 6 h(P<0.01).The cerebral blood flow in the model group was significantly lower than the control group at 1,3 and 6 h after MCAO(P<0.01),while for the EA group it was remarkably higher than the model group at the same time points(P<0.01).The expressions of Gq,CaM,IP3,DAG and[Ca^(2+)]i in the model group were significantly higher than the control group(P<0.05 or P<0.01),and those in the EA group were significantly lower than the model group at the same time points(P<0.05 or P<0.01).Conclusion:EA treatment at GV 26 can effectively decrease the over-expression of related factors of PI system in rats with acute cerebral infarction,improve cerebral autonomy movement,and alleviate cerebral vascular spasm.