Mitochondrial Oxidative Stress Enhances Vasoconstriction by Altering Calcium Homeostasis in Cerebrovascular Smooth Muscle Cells under Simulated Microgravity

Objective Exposure to microgravity results in postflight cardiovascular deconditioning in astronauts.Vascular oxidative stress injury and mitochondrial dysfunction have been reported during this process.To elucidate the mechanism for this condition,we investigated whether mitochondrial oxidative stress regulates calcium homeostasis and vasoconstriction in hindlimb unweighted(HU)rat cerebral arteries.Methods Three-week HU was used to simulate microgravity in rats.The contractile responses to vasoconstrictors,mitochondrial fission/fusion,Ca^(2+) distribution,inositol 1,4,5-trisphosphate receptor(IP3 R)abundance,and the activities of voltage-gated K+channels(KV)and Ca^(2+)-activated K+channels(BKCa)were examined in rat cerebral vascular smooth muscle cells(VSMCs).Results An increase of cytoplasmic Ca^(2+) and a decrease of mitochondrial/sarcoplasmic reticulum(SR)Ca^(2+) were observed in HU rat cerebral VSMCs.The abundance of fusion proteins(mitofusin 1/2[MFN1/2])and fission proteins(dynamin-related protein 1[DRP1]and fission-mitochondrial 1[FIS1])was significantly downregulated and upregulated,respectively in HU rat cerebral VSMCs.The cerebrovascular contractile responses to vasoconstrictors were enhanced in HU rats compared to control rats,and IP3 R protein/mRNA levels were significantly upregulated.The current densities and open probabilities of KV and BKCa decreased and increased,respectively.Treatment with the mitochondrial-targeted antioxidant mitoTEMPO attenuated mitochondrial fission by upregulating MFN1/2 and downregulating DRP1/FIS1.It also decreased IP3 R expression levels and restored the activities of the KV and BKCa channels.MitoTEMPO restored the Ca^(2+) distribution in VSMCs and attenuated the enhanced vasoconstriction in HU rat cerebral arteries.Conclusion The present results suggest that mitochondrial oxidative stress enhances cerebral vasoconstriction by regulating calcium homeostasis during simulated microgravity.

Pinocembrin inhibits angiotensinⅡ-induced vasoconstriction in a Ca^(2+)-dependent and Ca^(2+)-independent manner through blocking AT_1R in the rat aorta

OBJECTIVE To investigate the vasorelaxant effect of pinocembrin(5,7-dihydroxyflavanone),one of the main flavonoids in propolis,on angiotensinⅡ(AngⅡ)induced vasoconstriction and the molecular mechanism of action.METHODS The isometric vascular tone was measured in thoracic aortic rings from SD rat,and the effects of pinocembrin on the single dose and concentration cumulative response curves of AngⅡ were recorded.The binding of pinocembrin to the angiotensin type 1 receptor(AT1R)was studied by using molecule docking analysis.Intracellular[Ca2+]([Ca2+]i)was measured with Fura2/AM in VSMCs.The phosphorylation levels of myosin light chain 2(MLC2)and myosin phosphatase target unit 1(MYPT1),and protein level of Rho kinase 1(ROCK1)in the rat aortic rings were detected by Western blotting.RESULTS Pinocembrin was observed to inhibit AngⅡ-induced vasoconstriction in rat aortic rings with either intact or denuded endothelium.In endothelium-denuded tissues,pinocembrin(pD′2 4.28±0.15)counteracted the contractions evoked by cumulative concentrations of AngⅡ.In a docking model,pinocembrin showed effective binding at the active site of AT1R.Pinocembrin was shown to inhibit both AngⅡ-induced Ca2+ release from internal stores and Ca2+ influx.Moreover,the increase in the phosphorylation of MLC2 and MYPT1,and the increased protein level of ROCK1 induced by AngⅡ was blocked by pinocembrin.CONCLUSION Pinocembrin inhibits AngⅡ-induced rat aortic ring contraction in a Ca2+-dependent and Ca2+-independent manner via blocking AT1R.

Tacrolimus Inhibits Vasoconstriction by Increasing Ca^(2+) Sparks in Rat Aorta

The present study attempted to test a novel hypothesis that Ca^2＋ sparks play an important role in arterial relaxation induced by tacrolimus. Recorded with confocal laser scanning microscopy, tacrolimus（10 μmol/L） increased the frequency of Ca^2＋ sparks, which could be reversed by ryanodine（10 μmol/L）. Electrophysiological experiments revealed that tacrolimus（10 μmol/L） increased the large-conductance Ca^2＋-activated K＋ currents（BKCa） in rat aortic vascular smooth muscle cells（AVSMCs）, which could be blocked by ryanodine（10 μmol/L）. Furthermore, tacrolimus（10 and 50 μmol/L） reduced the contractile force induced by norepinephrine（NE） or KCl in aortic vascular smooth muscle in a concentration-dependent manner, which could be also significantly attenuated by iberiotoxin（100 nmol/L） and ryanodine（10 μmol/L） respectively. In conclusion, tacrolimus could indirectly activate BKCa currents by increasing Ca^2＋ sparks released from ryanodine receptors, which inhibited the NE- or KCl-induced contraction in rat aorta.

Reduction of photodynamic damage of blood vessels in the protected region by(–)-epigallocatechin gallate

Photodynamic therapy(PDT)has been increasingly used in the clinical treatment of neoplastic,inflammatory and infectious skin diseases.However,the generation of reactive oxygen species(ROS)may induce undesired side effects in normal tissue surrounding the treatment lesion,which is a big challenge for the clinical application of PDT.To date,(–)-Epigallocatechin gallate(EGCG)has been widely proposed as an antiangiogenic and antitumor agent for the protection of normal tissue from ROS-mediated oxidative damage.This study evaluates the regulation ability of EGCG for photodynamic damage of blood vessels during hematoporphyrin monomethyl ether(Hemoporfin)-mediated PDT.The quenching rate constants of EGCG for the triplet-state Hemoporfin and photosensitized 1O2 generation are determined to be 6.8×10^(8)M^(−1)S^(−1),respectively.The vasoconstriction of blood vessels in the protected region treated with EGCG hydrogel after PDT is lower than that of the control region treated with pure hydrogel,suggesting an efficiently reduced photodamage of Hemoporfin for blood vessels treated with EGCG.This study indicates that EGCG is an efficient quencher for triplet-state Hemoporfin and 1O2,and EGCG could be potentially used to reduce the undesired photodamage of normal tissue in clinical PDT.

Hypoxia in the pulmonary vein increases pulmonary vascular resistance independently of oxygen in the pulmonary artery

Introduction:Hypoxic pulmonary vasoconstriction(HPV)can be a challenging clinical problem.It is not fully elucidated where in the circulation the regulation of resistance takes place.It is often referred to as if it is in the arteries,but we hypothesized that it is in the venous side of the pulmonary circulation.Methods:In an open thorax model,pigs were treated with a veno-venous extra corporeal membrane oxygenator to either oxygenate or deoxygenate blood passing through the pulmonary vessels.At the same time the lungs were ventilated with extreme variations of inspired air from 5%to 100%oxygen,making it possible to make combinations of high and low oxygen content through the pulmonary circulation.A flow probe was inserted around the main pulmonary artery and catheters in the pulmonary artery and in the left atrium were used for pressure monitoring and blood tests.Under different combinations of oxygenation,pulmonary vascular resistance(PVR)was calculated.Results:With unchanged level of oxygen in the pulmonary artery and reduced inspired oxygen fraction lowering oxygen tension from 29 to 6.7 kPa in the pulmonary vein,PVR was doubled.With more extreme hypoxia PVR suddenly decreased.Combinations with low oxygenation in the pulmonary artery did not systematic influence PVR if there was enough oxygen in the inspired air and in the pulmonary veins.Discussion:The impact of hypoxia occurs from the alveolar level and forward with the blood flow.The experiments indicated that the regulation of PVR is mediated from the venous side.

Reversible cerebral vasoconstriction syndrome presenting as an isolated primary intraventricular hemorrhage

Background: Primary intraventricular hemorrhage is an uncommon cause of stroke and is often associated with longstanding, uncontrolled hypertension. Reversible cerebral vasoconstriction is also an uncommon condition characterized by reversible constriction of intracerebral vessels, which can lead to ischemic or hemorrhagic strokes. Case presentation: We describe a case of isolated primary intraventricular hemorrhage secondary to reversible cerebral vasoconstriction syndrome triggered by pseudoephedrine. Conclusions: Reversible cerebral vasoconstriction syndrome is a rare cause of primary intraventricular hemorrhage and should be considered in the differential in angiography-negative IVH when there is a history of vasoactive substance use.

Regulatory mechanisms of retinal ganglion cell death in normal tension glaucoma and potential therapies

Normal tension glaucoma(NTG)is a multifactorial optic neuropathy characterized by normal intraocular pressure,progressive retinal ganglion cell(RGC)death,and glaucomatous visual field loss.Recent studies have described the mechanisms underlying the pathogenesis of NTG.In addition to controlling intraocular pressure,neuroprotection and reduction of RGC degeneration may be beneficial therapies for NTG.In this review,we summarized the main regulatory mechanisms of RGC death in NTG,including autophagy,glutamate neurotoxicity,oxidative stress,neuroinflammation,immunity,and vasoconstriction.Autophagy can be induced by retinal hypoxia and axonal damage.In this process,ischemia can cause mutations of optineurin and activate the nuclear factor-kappa B pathway.Glutamate neurotoxicity is induced by the over-stimulation of N-methyl-D-aspartate membrane receptors by glutamate,which occurs in RGCs and induces progressive glaucomatous optic neuropathy.Oxidative stress also participates in NTG-related glaucomatous optic neuropathy.It impairs the mitochondrial and DNA function of RGCs through the apoptosis signal-regulating kinase-JUN N-terminal kinase pathway.Moreover,it increases inflammation and the immune response of RGCs.Endothelin 1 causes endothelial dysfunction and impairment of ocular blood flow,promoting vasospasm and glaucomatous optic neuropathy,as a result of NTG.In conclusion,we discussed research progress on potential options for the protection of RGCs,including TANK binding kinase 1 inhibitors regulating autophagy,N-methyl-D-aspartate receptor antagonists inhibiting glutamate toxicity,ASK1 inhibitors regulating mitochondrial function,and antioxidants inhibiting oxidative stress.In NTG,RGC death is regulated by a network of mechanisms,while various potential targets protect RGCs.Collectively,these findings provide insight into the pathogenesis of NTG and potential therapeutic strategies.

Acute renal failure with severe loin pain and patchy renal ischemia after anaerobic

BACKGROUND There are two known types of exercise-induced acute renal failure.One is the long-known myoglobinuria-induced acute renal failure due to severe rhabdomyolysis,and the other is the recently recognized non-myoglobinuria-induced acute renal failure with mild rhabdomyolysis.Exercise-induced acute renal failure was first reported in 1982.Non-myoglobinuria-induced acute renal failure is associated with severe low back pain and patchy renal vasoconstriction,and it is termed post-exercise acute renal failure because it usually occurs hours after exercise.It is also called acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise(ALPE).AIM To makes a significant contribution to medical literature as it presents a study that investigated a not-widely-known type of exercise-induced acute renal failure known as ALPE.METHODS We performed a database search selecting papers published in the English or Japanese language.A database search was lastly accessed on September 1,2022.The results of this study were compared with those reported in other case series.RESULTS The study evaluated renal hypouricemia as a key risk factor of ALPE.The development of ALPE is due to the sum of risk factors such as exercise,hypouricemia,nonsteroidal anti-inflammatory drugs,vasopressors,and dehydration.CONCLUSION In conclusion,hypouricemia plays a key role in the development of ALPE and is often associated with anaerobic exercise.The development of ALPE is a result of the cumulative effects of risk factors such as exercise,hypouricemia,NSAIDs,vasopressors,and dehydration.

Role of ROS/Kv/HIF Axis in the Development of Hypoxia-Induced Pulmonary Hypertension

Hypoxic pulmonary hypertension (HPH) is a common complication in patients with chronic obstructive pulmonary disease (COPD), sleep-disordered breathing, or dwellers in high altitude. The exact mechanisms underlying the development of HPH still remain unclear. Reactive oxygen species (ROS),hypoxia inducible factors (HIF), and potassium channels (KV) are believed as the main factors during the development of HPH. We propose that the “ROS/Kv/HIF axis” may play an important initiating role in the development of HPH. Being formed under a hypoxic condition, ROS affects the expression and function of HIFs or KV, and consequently triggers multiple downstream signaling pathways and genes expression that participate in promoting pulmonary vasoconstriction and arterial remodeling. Thus, further study determining the initiating role of “ROS/Kv/HIF axis” in the development of HPH could provide theoretic evidences to better understand the underlying mechanisms of HPH, and help identify new potential targets in the treatment of HPH.

In vivo observation of cerebral microcirculation after experimental subarachnoid hemorrhage in mice

Acute brain injury caused by subarachnoid hemorrhage is the major cause of poor prognosis. The pathology of subarachnoid hemorrhage likely involves major morphological changes in the microcirculation. However, previous studies primarily used fixed tissue or delayed injury models. Therefore, in the present study, we used in vivo imaging to observe the dynamic changes in cerebral microcirculation after subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by perforation of the bifurcation of the middle cerebral and anterior cerebral arteries in male C57/BL6 mice. The diameter of pial arterioles and venules was measured by in vivo fluorescence microscopy at different time points within 180 minutes after subarachnoid hemorrhage. Cerebral blood flow was examined and leukocyte adhesion/albumin extravasation was determined at different time points before and after subarachnoid hemorrhage. Cerebral pial microcirculation was abnormal and cerebral blood flow was reduced after subarachnoid hemorrhage. Acute vasoconstriction occurred predominantly in the arterioles instead of the venules. A progressive increase in the number of adherent leukocytes in venules and substantial albumin extravasation were observed between 10 and 180 minutes after subarachnoid hemorrhage. These results show that major changes in microcirculation occur in the early stage of subarachnoid hemorrhage. Our findings may promote the development of novel therapeutic strategies for the early treatment of subarachnoid hemorrhage.

Role of Voltage-gated Potassium Channels in Pathogenesis of Chronic Pulmonary Heart Disease

The influence of hypoxia on the activity of voltage-gated potassium channel in pulmonary artery smooth muscle cells （PASMCs） of rats and its roles in the pathogenesis of chronic pulmonary heart disease were investigated. Eighty male Sprague-Dawley rats were randomly allocated into control group （n=10）, acute hypoxic group （n=10）, and chronic hypoxic groups （n=60）. The chronic hypoxic groups were randomly divided into 6 subgroups （n=10 each） according to the chronic hypoxic periods. The rats in the control group were kept in room air and those in acute hypoxic group in hypoxia envi- ronmental chamber for 8 h. The rats in chronic hypoxic subgroups were kept in hypoxia environmental chamber for 8 h per day for 5, 10, 15, 20, 25, and 30 days, respectively. The mean pulmonary arterial pressure （mPAP）, right ventricular hypertrophy index （RVHI）, and the current of voltage-gated potas- sium channel （IK） in PASMCs were measured. Results showed that both acute and chronic hypoxia could decrease the IK in PASMCs of rats and the I-V relationship downward shifted to the right. And the peak Ir density at ＋60mV decreased with prolongation of hypoxia exposure. No significant difference was noted in the density oflK （at ＋60 mV） and I-V relationship between control group and chronic hy- poxic subgroup exposed to hypoxia for 5 days （P〉0.05）, but there was a significant difference between control group and chronic hypoxic subgroup exposed to hypoxia for 10 days （P〈0.05）. Significant dif- ferences were noted in the IK density （at ＋60 mV） and I-V relationships between control group and chronic hypoxic subgroups exposed to hypoxia for 20 days and 30 days （P〈0.01）. Compared with con- trol rats, the mPAP and RVHI were significantly increased after chronic exposure to hypoxia for 10 days （P〈0.05）, which were further increased with prolongation of hypoxia exposure, and there were signifi- cant differences between control group and chronic hypoxic subgroups exposed to hypoxia for 20 days and 30 days （P〈0.01）. Both the mPAP and the RVHI were negatively correlated with the density OflK （r---0.89769 and -0.94476, respectively, both P〈0.01）. It is concluded that exposure to hypoxia may cause decreased activity of voltage-gated potassium channel, leading to hypoxia pulmonary vasocon- striction （HPV）. Sustained HPV may result in chronic pulmonary hypertension, even chronic pulmonary heart disease, contributing to the pathogenesis of chronic pulmonary heart disease.

Monitoring of time-resolved singlet oxygen luminescence at 1270 nm by an optical fiber detection system

Singlet oxygen(^(1)O_(2))is the main cytotoxic substance in Type II photodynamic therapy(PDT).The luminescence of ^(1)O_(2) at 1270nm is extremely weak with a low quantum yield,making the direct detection of'O2 at 1270 nm very challenging.In this study,a set of highly sensitive optical fiber detection system is built up to detect the luminescence of photosensitized ^(1)O_(2) We use this system to test the luminescence characteristics of ^(1)O_(2) in pig skin tissue ex vrivo and mouse auricle skin in vivo.The experimental results show that the designed system can quantitatively detect photosensitized ^(1)O_(2) luminescence.The ^(1)O_(2) luminescence signal at 1270 nm is successfully detected in pig skin exr vivo.Compared with RB in an aqueous solution,the lifetime of ^(1)O_(2) increases to 17.4±12pus in pig skin tissue ex vivo.Experiments on living mice suggest that an enhancement of ^(1)O_(2) intensity with the increase of the TMPyP concentration.When the dose is 25 mg/kg,the vasoconstriction can reach more than 80%。The results of this study hold the potential application for clinical PDT dose monitoring using an optical fiber detection system.

Amniotic fluid embolism:literature review and an integrated concept of pathomechanism

Literature concerning procoagulant activity of the amniotic fluid and pathomechanism of amniotic fluid embolism (AFE) was surveyed and a new concept of its pathogenesis, called the integrated concept of AFE, was presented. According to this concept, two components of the amniotic fluid are involved: (i) apoptosis-affected amniotic cells showing a special role in the initiation of disseminated intravascular coagulation (DIC) and (ii) leukotrienes (formerly called slow-reacting substances), inducing bronchial and pulmonary vascular smooth muscle contraction. Although each of these components initiates a different pathogenic pathway, they both lead to the formation of a mechanical barrier on blood flow through the lungs (amniotic debris + microemboli) and/or functional barrier (pulmonary vasoconstriction). An old dilemma, concerning indications for heparin therapy in AFE was recalled in the light of the new concept.

Laparoscopic-assisted instillation of epinephrine and levobupivacaine enables cornual excision and anatomical reconstruction in unruptured cornual pregnancy

The objective of this report is to describe the possible use of intramiometrial vasoconstrictive agents for laparoscopic management of interstitial pregnancy and the consequences in anatomical results and reproductive outcomes. Cornual resection can be performed by laparoscopy, but the high vascularization of this area may result in profuse bleeding and laparoscopic suturing under these conditions might be impossible for the majority of the surgeons. We present a case that describes the possible use of intramiometrial instillation of a solution of diluted epinephrine and levobupivacaine under laparoscopic guidance that permitted a bloodless cornual excision with complete reconstruction. Vasoactive agents might have potentially serious cardiovascular side effects and the correct election of the active principle and the dosage is essential to reduce the risk of the surgery and obtain good anatomical results and reproductive outcomes. In conclusion, unruptured interstitial pregnancies can be managed successfully with intramyometrial instillation of epinephrine and bupivacaine. This simple technique is particularly attractive as it facilitates anatomical reconstruction of the cornual area, gives enough time to perform a complete suture of the defect and reduces the risk of laparotomic conversion.

Mechanisms underlying the vascular relaxation activities of Zingiber officinale var. rubrum in thoracic aorta of spontaneously hypertensive rats

Objective: To evaluate vasorelaxant and vasoconstriction effects of Zingiber officinale var. rubrum(ZOVR)on live rats and isolated aortic rings of spontaneously hypertensive rats(SHRs).Methods: Extracts of ZOVR were subjected to in-vivo antihypertensive screening using noninvasive blood pressures in SHRs. The most potent extract, ZOVR petroleum ether extract(ZOP) was then fractionated using n-hexane, chloroform and water. Isolated thoracic aortic rings were harvested and subjected to vascular relaxation studies of n-hexane fraction of ZOP(HFZOP) with incubation of different antagonists such as Nω-nitro-L-arginine methyl ester(L-NAME, 10 μmol/L), indomethacin(10 μmol/L), methylene blue(10 μmol/L), atropine(1 μmol/L), glibenclamide(10 μmol/L), prazosin(0.01 μmol/L), and propranolol(1 μmol/L).Results: During the screening of various ZOVR extracts, ZOP produced the most reduction in blood pressures of SHRs and so did HFZOP. HFZOP significantly decreased phenylephrine-induced contraction and enhanced acetylcholine-induced relaxation. L-NAME, indomethacin, methylene blue, atropine, and glibenclamide significantly potentiated the vasorelaxant effects of HFZOP. Propranolol and prazosin did not alter the vasorelaxant effects of HFZOP. HFZOP significantly suppressed the Ca2+-dependent contraction and influenced the ratio of the responses to phenylephrine in Ca2+-free medium.Conclusion: This study demonstrates that ZOP may exert an antihypertensive effect in the SHR model. Its possible vascular relaxation mechanisms involve nitric oxide and prostacyclin release, activation of cGMP-KATP channels, stimulation of muscarinic receptors, and transmembrane calcium channel or Ca2+release from intracellular stores. Possible active compounds that contribute to the vasorelaxant effects are 6-gingerol, 8-gingerol and 6-shogaol.

ERK signaling mediates enhanced angiotensin II-induced rat aortic constriction following chronic intermittent hypoxia

Background Obstructive sleep apnea （OSA） has been recognized as an independent risk factor for systemic hypertension. The study investigated the functional consequences of chronic intermittent hypoxia （CIH） on aortic constriction induced by angiotensin II （Ang II） and the possible signaling involving ERK1/2 and contractile proteins such as myosin light chain kinase （MLCK）, myosin phosphatase targeting subunit （MYPT1） and myosin light chain （MLC）. Methods Male Wistar rats were randomly divided into CIH group and normoxia group and exposed to either CIH procedure or air-air cycles. Phosphorylation of ERK1/2, MYPT1 and MLC was assessed by Western blotting following constrictor studies in the presence or absence of PD98059 （10 μmol/L）. Results CIH-exposure resulted in more body weight gain and elevated blood pressure, which could be attenuated by pretreatment with PD98059. Endothelium-removed aortic rings from CIH rats exhibited higher constrictor sensitivity to Ang II （Emax： （138.56±5.78）% versus （98.45±5.31）% of KCI; pD2：7.98±0.14 versus 8.14±0.05, respectively）. CIH procedure exerted complex effects on ERK expressions （total ERK1/2 decreased whereas the ratio of phosphorylated to total ERK1/2 increased）. CIH aortas had higher MLCK mRNA and basal phosphorylation of MYPT1 and MLC. In parallel to greater increases in phosphorylation of ERK1/2, MYPT1 and MLC, Ang II-induced aortic constriction was significantly enhanced in CIH rats, which was largely reversed by PD98059. However vascular constriction of normoxia rats remained unchanged despite similar but smaller changing tendency of proteins phosphorylation. Conclusion These data suggest that CIH exposure results in aortic hyperresponsiveness to Ang II, presumably owing to more activated ERK1/2 signaling pathway.

Vasorelaxant effects of 50 commonly used traditional herbal prescriptions on isolated rat aortic rings

OBJECTIVE:To investigate the vasorelaxant activities of 50 common traditional herbal prescriptions(THPs)on isolated rat aortic rings.METHODS:An electric extractor was used to extract THPs.Rat aortic rings were precontracted using phenylephrine in organ chambers containing Krebs-Henseleit solution.Decoctions of THPs were added in increasing concentrations(10-1000μg/mL)to investigate vasorelaxant activities.The vasorelaxant effects of THPs were calculated as percentage of contraction in response to phenylephrine.RESULTS:Several THPs such as Tianwangbuxin Dan,Banxiaxiexin Tang,and Mahuang Tang,significantly relaxed precontracted aortic rings.In contrast,Xiaochaihu Tang,Shensuyin,and Guizhifuling Wan significantly contracted aortic rings.Furthermore,these THPs increasingly relaxed or contracted aortic rings relaxed by amlodipine.CONCLUSION:Our findings suggest that hypertension can be treated using THPs.However some THPs can counteract treatment of hypertension.Further studies should be developed on use of THPs for treatment of hypertension are critical,and guidelines for use of traditional herbal medicines to treat hypertension.

Contribution of L-type Ca^(2+) channel to the regulation of coronary arterial smooth muscle contraction is different in rats and mice

Background L-type calcium channel participates in the regulation of a variety of physical and pathological process. In vasculature, it mainly mediated agonist-induced vascular smooth muscle contraction. However, it is not clear whether there are differences in L-type calcium channel mediated vessel responses to certain vasoconstrictors among different species. Methods The coronary arteries were dissected from the heart of rats and mice respectively. The coronary arterial ring contraction was measured by Multi Myograph System. Results Endothelin-1, U46619 and 5-HT could produce concentration-dependent vasoconstriction of coronary arterial rings from rats and mice. Compared with rats, the vessel rings of mice were more sensitive to ET-1 and U46619, and less sensitive to 5-HT. The L-type Ca2~ channel blocker nifedipine could significantly inhibit the coronary artery contractions induced by ET-1, U46619 and 5-HT. The inhibitory effect of i ixM nifedipine on ET-1 and 5-HT-induced coronary artery contractions were stronger in mice than in rats, but its effect on U46619 induced-vessel contractions was much weaker in mice than in rats. Conclusions L-type Ca2＋ channel plays an important role in the coronary arterial contraction, but the responses to vasoconstrictor and L-type Ca2＋ channel blocker are different between rats and mice, thus suggesting that the coronary arteries of rats and mice have different biological characteristics.