Engineering of fibrin-based functional and implantable small-diameter blood vessels

2005 ◽  
Vol 288 (3) ◽  
pp. H1451-H1460 ◽  
Author(s):  
Daniel D. Swartz ◽  
James A. Russell ◽  
Stelios T. Andreadis
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Mechanical Strength ◽  
Blood Vessels ◽  
Vascular Reactivity ◽  
Small Diameter ◽  
Matrix Remodeling ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Jugular Veins

We engineered implantable small-diameter blood vessels based on ovine smooth muscle and endothelial cells embedded in fibrin gels. Cylindrical tissue constructs remodeled the fibrin matrix and exhibited considerable reactivity in response to receptor- and nonreceptor-mediated vasoconstrictors and dilators. Aprotinin, a protease inhibitor of fibrinolysis, was added at varying concentrations and affected the development and functionality of tissue-engineered blood vessels (TEVs) in a concentration-dependent manner. Interestingly, at moderate concentrations, aprotinin increased mechanical strength but decreased vascular reactivity, indicating a possible relationship between matrix degradation/remodeling, vasoreactivity, and mechanical properties. TEVs developed considerable mechanical strength to withstand interpositional implantation in jugular veins of lambs. Implanted TEVs integrated well with the native vessel and demonstrated patency and similar blood flow rates as the native vessels. At 15 wk postimplantation, TEVs exhibited remarkable matrix remodeling with production of collagen and elastin fibers and orientation of smooth muscle cells perpendicular to the direction of blood flow. Implanted vessels gained significant mechanical strength and reactivity that were comparable to those of native veins. Our work demonstrates that fibrin-based TEVs hold significant promise for treatment of vascular disease and as a biological model for studying vascular development and pathophysiology.

scholarly journals Aristoteline, an Indole-Alkaloid, Induces Relaxation by Activating Potassium Channels and Blocking Calcium Channels in Isolated Rat Aorta

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2748 ◽  
Author(s):  
Fernando Romero ◽  
Javier Palacios ◽  
Ignacio Jofré ◽  
Cristian Paz ◽  
Chukwuemeka R. Nwokocha ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Vascular Reactivity ◽  
Soluble Guanylate Cyclase ◽  
Indole Alkaloid ◽  
Soluble Guanylyl Cyclase ◽  
Rat Aorta ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cav1.2 Channels ◽  
Aristotelia Chilensis

Alkaloids derived from plants have shown great medicinal benefits, and are often reported for their use in cardiovascular disease management. Aristotelia chilensis (Molina) Stuntz (Maqui) has shown important medicinal properties in traditional useage. In this study, we evaluated the effect of the indole-alkaloid aristoteline (ARI), isolated from leaves of Maqui, on vascular reactivity of isolated aortic rings from normotensive rats. ARI induced relaxation (100%) in a concentration-dependent manner in intact or denuded-endothelium aortic rings pre-contracted with phenylephrine (PE; 1 μM). However, a specific soluble guanylyl cyclase inhibitor (ODQ; 1 μM) significantly reduced the relaxation to ARI in aortic rings pre-contracted with PE. In the presence of ARI, the contraction induced by KCl or PE was significantly (p < 0.05) decreased. Interestingly, the potassium channel blockade with 10 μM BaCl2 (Kir), 10 μM glibenclamide (KATP), 1 mM tetraethylammonium (TEA; KCa1.1), or 1 mM 4-aminopyridine (4-AP; Kv) significantly (p < 0.05) reduced the ARI-induced relaxation. ARI significantly (p < 0.05) reduced the contractile response to agonist of CaV1.2 channels (Bay K8644; 10 nM), likely reducing the influx of extracellular calcium through plasma membrane. The mechanisms associated with this process suggest an activation of the potassium channels, a calcium-induced antagonism and endothelium independent vasodilation that possibly involves the nitric oxide-independent soluble guanylate cyclase pathway.

Sevoflurane Inhibits Guanosine 5′-[γ-thio]triphosphate–stimulated, Rho/Rho-kinase–mediated Contraction of Isolated Rat Aortic Smooth Muscle

2003 ◽  
Vol 99 (3) ◽  
pp. 646-651 ◽  
Author(s):  
Jingui Yu ◽  
Koji Ogawa ◽  
Yasuyuki Tokinaga ◽  
Yoshio Hatano
Keyword(s):  
Smooth Muscle ◽  
Kinase Inhibitor ◽  
Isometric Force ◽  
Rho Kinase ◽  
Force Transducer ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Aortic Smooth Muscle ◽  
Gamma S ◽  
Kinase Pathway

Background The Rho/Rho-kinase signaling pathway plays an important role in mediating Ca2+ sensitization of vascular smooth muscle. The effect of anesthetics on Rho/Rho-kinase-mediated vasoconstriction has not been determined to date. This study is designed to examine the possible inhibitory effects of sevoflurane on the Rho/Rho-kinase pathway by measuring guanosine 5'-[gamma-thio]triphosphate (GTP gamma S)-stimulated contraction and translocation of RhoA (one of the three Rho subtypes) and Rock-2 (one of the two Rho-kinase subtypes) from the cytosol to the membrane in rat aortic smooth muscle. Methods GTP gamma S-induced contraction of rat aortic endothelium-denuded rings was measured using an isometric force transducer, and GTP gamma S-stimulated membrane translocation of RhoA and Rock-2 in smooth muscle cells was detected with Western blotting in the presence and absence of sevoflurane. Results GTP gamma S (10(-4) m) induced a sustained contraction, which was significantly inhibited by the Rho-kinase inhibitor, Y27632 (3 x 10(-6) m). Before treatment with GTP gamma S, RhoA and Rock-2 were detected primarily in the cytosolic fraction. GTP gamma S (10(-4) m) stimulated the translocation of RhoA and Rock-2 from the cytosol to the membrane, which was sustained for more than 60 min. Sevoflurane (1.7, 3.4, and 5.1%) concentration dependently inhibited the GTP gamma S-induced constriction of rat aortic smooth muscle with a reduction of constriction of 52-75% (P &lt; 0.01, n = 8), and attenuated the translocation of RhoA and Rock-2 by 31-66% and 34-78%, respectively (P &lt; 0.05-0.01, respectively; n = 4). Conclusion The current findings show that sevoflurane depresses the GTP gamma S-stimulated contraction and translocation of both Rho and Rho-kinase from the cytosol in a concentration-dependent manner, indicating that sevoflurane is able to inhibit vasoconstriction mediated by the Rho/Rho-kinase pathway in rat aortic smooth muscle.

Vasodilator drugs and peripheral vascular disorders

1964 ◽  
Vol 2 (6) ◽  
pp. 22-24
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Nicotinic Acid ◽  
Cerebrovascular Disease ◽  
Blood Vessels ◽  
Ethyl Alcohol ◽  
Peripheral Vascular ◽  
Future Issue ◽  
Vascular Disorders ◽  
Improve Blood Flow

Many drugs are claimed to be effective vasodilators which can improve blood flow in peripheral vascular disorders. Among them are noradrenaline antagonists such as tolazoline (Priscol - Ciba), azapetine (Ilidar - Roche) and phenoxybenzamine (Dibenyline - SKF), and drugs which act directly on the smooth muscle of blood vessels, such as isoxsuprine (Duvadilan - Crookes; Dilavase - Organon), nicotinyl alcohol (Ronicol - Roche), and cyclandelate (Cyclospasmol - Camden). Nicotinic acid, papaverine and ethyl alcohol are also used as vasodilators. Claims that cyclandelate and certain other drugs are indicated in the treatment of cerebrovascular disease will be discussed in a future issue.

Differential blockade of agonist- and depolarization-induced 45Ca2+ influx in smooth muscle cells

1989 ◽  
Vol 257 (4) ◽  
pp. C607-C611 ◽  
Author(s):  
A. Wallnofer ◽  
C. Cauvin ◽  
T. W. Lategan ◽  
U. T. Ruegg
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Gamma S ◽  
Ca2 Channels ◽  
Stimulation Of

ATP stimulated 45Ca2+ influx in rat aortic smooth muscle cells in a concentration-dependent manner (EC50 = 3.6 +/- 0.5 X 10(-7) M). ADP and GTP were less effective than ATP in stimulating 45Ca2+ influx; AMP was weakly active and the adenosine agonist 5'-(N-ethyl-carboxamido)-adenosine (NECA) had no effect. ATP gamma S was about equieffective with ATP, whereas alpha,beta-methylene-ATP (APCPP) did not induce 45Ca2+ influx. Stimulation of 45Ca2+ influx by ATP was not abolished by the dihydropyridine Ca2+ channel antagonist darodipine (PY 108-068), which completely blocked depolarization-induced 45Ca2+ influx. Inorganic cations (La3+, Cd2+, Co2+, Ni2+, Mn2+, and Mg2+) were able to inhibit both agonist- and depolarization-induced 45Ca2+ influx. Cd2+, however, was approximately 20 times more selective in blocking K+-stimulated than agonist-stimulated 45Ca2+ influx. These data indicate that ATP-stimulated Ca2+ influx in rat aortic smooth muscle cells is resistant to darodipine but is reduced by La3+, Cd2+, and other inorganic blockers of Ca2+ channels.

Control of neurotransmission by prostaglandins in canine trachealis smooth muscle

1984 ◽  
Vol 57 (1) ◽  
pp. 129-134 ◽  
Author(s):  
E. H. Walters ◽  
P. M. O'Byrne ◽  
L. M. Fabbri ◽  
P. D. Graf ◽  
M. J. Holtzman ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Prostaglandin E2 ◽  
Electrical Field Stimulation ◽  
Tracheal Smooth Muscle ◽  
Dependent Manner ◽  
Field Stimulation ◽  
Electrical Field ◽  
Similar Time ◽  
Concentration Dependent Manner ◽  
Contractile Responses

Contractile responses of canine tracheal smooth muscle to electrical field stimulation diminished over a 2-h period of incubation. However, addition of indomethacin (10(-5) M) for a similar time not only prevented this inhibition of contractile response, but actually markedly increased the response to electrical field stimulation, suggesting that prostaglandins were responsible for the time-dependent inhibition. Measured prostaglandin E2 increased in the tissue bath over 2 h in control tissues. Addition of prostaglandin E2 to the tissue produced similar inhibition of contractile responses to electrical field stimulation in a concentration-dependent manner. In contrast, incubation alone, treatment with indomethacin, or addition of prostaglandin E2 had little, if any, effect on contractions induced by acetylcholine. We conclude that the release of prostaglandins from canine tracheal smooth muscle that occurs with time has a predominantly inhibitory effect on cholinergic neurotransmission at a prejunctional site.

Neural and myogenic effects of cyclooxygenase products on canine bronchial smooth muscle

1995 ◽  
Vol 268 (1) ◽  
pp. L47-L55 ◽  
Author(s):  
A. P. Abela ◽  
E. E. Daniel
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Electrical Field Stimulation ◽  
Resting Membrane Potential ◽  
Dependent Manner ◽  
Ach Release ◽  
Concentration Dependent Manner ◽  
Excitatory Junction Potentials ◽  
Pg E2 ◽  
Large Contraction

In canine bronchi bathed in 10(-6) M indomethacin (IDM), prostaglandin (PG) E2 inhibited electrical field stimulation (EFS)- and acetylcholine (ACh)-mediated contractions and excitatory junction potentials (EJP) in a concentration-dependent manner without altering the resting membrane potential. EFS-induced EJPs were abolished at 10(-7) M PGE2, which shifted responses to ACh 10-fold rightward. Thus PGE2 predominantly inhibited the release of ACh and secondarily decreased smooth muscle response to ACh. U-46619, an analogue of thromboxane A2 (TxA2), initiated tetrodotoxin- and atropine-insensitive contractions in a concentration-dependent manner. U-46619 (10(-9) M) did not alter significantly EFS- or ACh-stimulated contractions and potentiated EFS amplitude of EJPs without depolarizing muscle cells. Either prejunctional activation of ACh release by TxA2 or postjunctional potentiation of the response to ACh can explain these findings. U-46619 (<or = 10(-8) M) depolarized the membrane potential, initiating oscillations accompanied by a large contraction. Addition of 10(-8) M nitrendipine, but not tetraethylammonium (25 mM), blocked the oscillations selectively. Other prostanoids (PGD2, PGI2, and PGF2 alpha) had no significant effects on canine bronchi. In the absence of IDM, PGE2 accumulated, EFS contractions decreased with time, and EJPs disappeared. We conclude that in canine bronchi PGE2 predominantly inhibits ACh release and endogenous PGE2 acts similarly, whereas TxA2 excites, probably at postjunctional sites.

GPR43 REGULATES SODIUM BUTYRATE-INDUCED ANGIOGENESIS AND MATRIX REMODELING

2020 ◽  
Author(s):  
Pollyana Ribeiro Castro ◽  
Lucas Felipe Fernandes Bittencourt ◽  
Sébastien Larochelle ◽  
Silvia Passos Andrade ◽  
Charles Reay Mackay ◽  
...  
Keyword(s):  
Sodium Butyrate ◽  
Granulation Tissue ◽  
Local Treatment ◽  
Dermal Fibroblasts ◽  
Matrix Remodeling ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Fibrovascular Tissue

Butyrate is a short-chain fatty acid (SCFA) derived from microbiota and is involved in a range of cell processes in a concentration-dependent manner. Low concentrations of sodium butyrate (NaBu) was shown to be proangiogenic. However, the mechanisms associated with these effects are not yet fully known. Here, we investigated the contribution of the SCFA receptor GPR43 in the proangiogenic effects of local treatment with NaBu and its effects on matrix remodeling using the sponge-induced fibrovascular tissue model in mice lacking the GPR43 gene (GPR43-KO) and the wild-type (WT). We demonstrated that NaBu (0.2 mM intraimplant) treatment enhanced the neovascularization process, blood flow, and VEGF levels in a GPR43-dependent manner in the implants. Moreover, NaBu was able to modulate matrix remodeling aspects of the granulation tissue such as proteoglycans production, collagen deposition and α-SMA expression in vivo, besides to increase TGF-b1 levels in the fibrovascular tissue, in a GPR43-dependent manner. Interestingly, NaBu directly stimulated L929 murine fibroblasts migration, and TGF-β1 and collagen production in vitro. GPR43 was found to be expressed in human dermal fibroblasts, myofibroblasts and endothelial cells. Overall, our findings evidence that the metabolite-sensing receptor GPR43 contributes to the effects of low dose of NaBu in inducing angiogenesis and matrix remodeling during granulation tissue formation. These data provide important insights for the proposition of new therapeutic approaches based on NaBu, beyond the highly explored intestinal, anti-inflammatory, and anti-cancer purposes, as a local treatment to improve tissue repair, particularly, by modulating granulation tissue components.

Effects of estrogen on cerebral blood flow and pial microvasculature in rabbits

2000 ◽  
Vol 279 (3) ◽  
pp. H1208-H1214 ◽  
Author(s):  
M. T. Littleton-Kearney ◽  
D. M. Agnew ◽  
R. J. Traystman ◽  
P. D. Hurn
Keyword(s):  
Blood Flow ◽  
Estrogen Receptor ◽  
Cerebral Blood Flow ◽  
Receptor Activation ◽  
Receptor Subtypes ◽  
Dependent Manner ◽  
Pial Arteries ◽  
Concentration Dependent Manner ◽  
Cranial Window ◽  
Pial Arterioles

We tested the hypothesis that intracarotid estrogen infusion increases cerebral blood flow (CBF) in a concentration-dependent manner and direct application of estrogen on pial arterioles yields estrogen receptor-mediated vasodilation. Rabbits of both genders were infused with estrogen via a branch of the carotid artery. Estrogen doses of 20 or 0.05 μg · ml−1 · min−1 were used to achieve supraphysiological or physiological plasma estrogen levels, respectively. CBF and cerebral vascular resistance were determined at baseline, during the infusion, and 60-min postinfusion, and effects on pial diameter were assessed via a cranial window. Pial arteriolar response to estrogen alone and to estrogen after administration of tamoxifen (10−7), an antiestrogen drug that binds to both known estrogen receptor subtypes, was tested. No gender differences were observed; therefore, data were combined for both males and females. Systemic estrogen infusion did not increase regional CBF. Estradiol dilated pial arteries only at concentrations ranging from 10−4–10−7 M ( P ≤ 0.05). Pretreatment with tamoxifen alone had no effect on arteriolar diameter but inhibited estrogen-induced vasodilation ( P < 0.001). Our data suggest that estrogen does not increase CBF under steady-state conditions in rabbits. In the pial circulation, topically applied estradiol at micromolar concentrations dilates vessels. The onset is rapid and dependent on estrogen receptor activation.

Regulation of KCa-channel activity by cyclic ADP-ribose and ADP-ribose in coronary arterial smooth muscle

1998 ◽  
Vol 275 (3) ◽  
pp. H1002-H1010 ◽  
Author(s):  
Pin-Lan Li ◽  
Ai-Ping Zou ◽  
William B. Campbell
Keyword(s):  
Smooth Muscle ◽  
Time Course ◽  
Control Level ◽  
Internal Surface ◽  
Threshold Concentration ◽  
Dependent Manner ◽  
Channel Activity ◽  
Arterial Smooth Muscle ◽  
Concentration Dependent Manner ◽  
Cyclic Adp Ribose

The enzymatic pathway responsible for the production and metabolism of cyclic ADP-ribose (cADP-R) in small bovine coronary arteries was characterized, and the role of cADP-R and ADP-ribose (ADP-R) in the regulation of the activity of large-conductance Ca2+-activated K+(KCa) channels was determined in vascular smooth muscle cells (SMC) prepared from these vessels. We found that cADP-R and ADP-R were produced when the coronary arterial homogenates were incubated with 1 mM β-NAD. The time course of the enzyme reactions showed that the maximal conversion rate (1.37 ± 0.03 nmol ⋅ min−1 ⋅ mg protein−1) of β-NAD to cADP-R was reached after 3 min of incubation. As incubation time was prolonged, the production of ADP-R was increased to a maximal rate of 3.66 ± 0.03 nmol ⋅ min−1 ⋅ mg protein−1, whereas cADP-R production decreased. Incubation of the homogenate with cADP-R produced a time-dependent increase in the synthesis of ADP-R. Comparison of coronary arterial microsomes with cytosols shows that the production of both cADP-R and ADP-R in microsomes was significantly greater. In excised inside-out membrane patches of single coronary SMC, the KCa channels were activated when β-NAD, the precursor for both cADP-R and ADP-R, was applied to the internal surface. This effect of β-NAD may be associated with the production of ADP-R, because the KCa-channel activity was increased by ADP-R in a concentration-dependent manner. The open-state probability of the KCa channels increased from a control level of 0.08 ± 0.03 to 0.17 ± 0.05 even at the lowest ADP-R concentration (0.1 μM) studied. However, cADP-R reduced the KCa-channel activity, and the threshold concentration of cADP-R that decreased the average channel activity of the KCa channels was 1 μM. These results provide evidence that cADP-R is produced and metabolized in the coronary arterial smooth muscle and that a cADP-R/ADP-R pathway participates in the control of the KCa-channel activity in vascular SMC.

Role of IL-4, IL-13, and STAT6 in inflammation-induced hypercontractility of murine smooth muscle cells

2002 ◽  
Vol 282 (2) ◽  
pp. G226-G232 ◽  
Author(s):  
Hirotada Akiho ◽  
Patricia Blennerhassett ◽  
Yikang Deng ◽  
Stephen M. Collins
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Trichinella Spiralis ◽  
Muscle Cells ◽  
Dependent Manner ◽  
T Helper ◽  
Concentration Dependent Manner ◽  
T Helper 2 ◽  
Muscularis Externa

T helper 2 (Th2) cytokines interleukin (IL)-4 and IL-13, which activate signal transducer and activator of transcription 6 (STAT6) are expressed in the muscularis externa during nematode infection and are candidate mediators of the associated hypercontractility. To determine the locus of action of these cytokines, we examined the IL-4- and IL-13-induced hypercontractility of the isolated muscle cells from STAT6 +/+ and STAT6 −/− mice. We compared the results with cells isolated from Trichinella spiralis-infected STAT6 +/+ and STAT6 −/− mice. Carbamylcholine chloride (Carbachol) induced the contraction of jejunal muscle cells in a concentration-dependent manner maximal contraction (Rmax26.7 ± 1.9%). Cells from T. spiralis-infected STAT6 −/− mice showed the hypertrophy (cell lengths 41.4 ± 0.8 to 89.0 ± 8.7 μm) and hypercontractility (Rmax37.5 ± 1.3%) induced by infection. IL-4Rα mRNA was detected in dispersed smooth muscle cells. Incubation of longitudinal muscle-myenteric plexus (LMMP) with IL-4 and IL-13 enhanced Carbachol-induced muscle contraction (Rmax35.5 ± 1.9 and 32.4 ± 2.9%, respectively). Incubation of LMMP from STAT6 −/− mice with IL-4 did not enhance the contraction. The hypercontractility in T. spiralis-infected mice was attenuated in STAT6 −/− mice ( P < 0.02). These results indicate both IL-4 and IL-13 induce hypercontractility of muscle cells via the STAT6 pathway, and this is the basis for hypercontractility observed in T. spiralis-infected mice.

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