The dog common carotid artery: a sensitive bioassay for studying vasodilator effects of substance P and of kinins

1980 ◽  
Vol 58 (10) ◽  
pp. 1234-1244 ◽  
Author(s):  
R. Couture ◽  
P. Gaudreau ◽  
S. St-Pierre ◽  
D. Regoli
Keyword(s):  
Substance P ◽  
Carotid Artery ◽  
Common Carotid Artery ◽  
Smooth Muscles ◽  
Vascular Smooth Muscles ◽  
Low Concentrations ◽  
Pharmacological Preparation ◽  
The Common ◽  
High Concentrations

In order to develop a sensitive pharmacological preparation which would allow the measurement of the inhibitory effects of kinins and substance P (SP) in vascular smooth muscles, several large arteries of the dog were studied in vitro. The common carotid artery was found to be one of the most sensitive preparations to SP and kinins. When contracted with low concentrations of noradrenaline (between 3.0 × 10−8 and 3.0 × 10−7 M), this artery responds to SP (6.5 × 10−11 − 6.5 × 10−9 M) and bradykinin (BK) (8.1 × 10−11 − 9.1 × 10−8 M) with relaxations that are proportional to the concentrations of the two peptides. SP and BK appear to exert their relaxant effects through the activation of specific receptors as the exposure of the common carotid artery to concentrations of [Leu8]-angiotensin II, propranolol, methysergide, cimetidine, or atropine sufficient to inhibit the effects of the corresponding agonists do not affect the relaxing effect of SP and BK. [Leu8]-des-Arg9-BK (1.0 × 10−s M), indomethacin (2.8 × 10−5 M), and lioresal (4.7 × 10−5 M) are also inactive. When the dog common carotid artery is desensitized with high concentrations of SP, BK, eledoisin, and physalaemin a cross-desensitization is observed only between SP and physalaemin. These results support the conclusion that SP and kinins act on different receptors. The order of potency of kinins is the following: BK = [Tyr(Me)8]-BK > des-Arg9-BK, suggesting that the receptor for kinins is of the B2 type. The order of potency of peptides related to SP is SP > C-terminal 4-11 > C-terminal hexapeptide 6-11, similar to that observed in other vascular preparations.The results summarized in this paper indicate that the dog common carotid artery is a preparation sensitive to SP and BK and useful for studying the relaxant effect of these two peptides on vascular smooth muscles.

Effects of kinins on isolated blood vessels. Role of endothelium

1982 ◽  
Vol 60 (12) ◽  
pp. 1580-1583 ◽  
Author(s):  
D. Regoli ◽  
J. Mizrahi ◽  
P. D'Orléans-Juste ◽  
S. Caranikas
Keyword(s):  
Arachidonic Acid ◽  
Carotid Artery ◽  
Common Carotid Artery ◽  
Smooth Muscles ◽  
Rabbit Aorta ◽  
Arachidonic Acid Metabolism ◽  
Arachidonic Acid Cascade ◽  
Vascular Smooth Muscles ◽  
Acid Metabolites

Bradykinin (BK) and des-Arg9-BK were used to determine whether the stimulatory and inhibitory actions of the kinins in various isolated vessels require the presence of endothelium and may be mediated by arachidonic acid metabolites. It was found that the presence of intact endothelium is required only for the relaxation of the dog common carotid artery in response to bradykinin. Stimulatory actions of both BK and des-Arg9-BK in arterial (rabbit aorta) and venous (rabbit jugular and mesenteric vein) smooth muscle do not require the presence of endothelium. Inhibition of the arachidonic acid cascade at various levels affects the relaxing action of acetylcholine (rabbit aorta and dog common carotid artery) while being inactive against both the relaxing (dog common carotid artery) and contractile actions (rabbit aorta, rabbit jugular and mesenteric veins) of bradykinin and des-Arg9-BK. Inhibitors of the arachidonic acid cascade also do not affect the inhibitory action of isopropylnoradrenaline on the rabbit aorta. The present results indicate that stimulant actions of kinins in isolated vascular smooth muscles do not require the presence of endothelium. Endothelium is required for the inhibitory actions of acetylcholine and bradykinin but not for that of isopropylnoradrenaline on the dog carotid artery. Moreover, the inhibition of arachidonic acid metabolism only affects the response of isolated vessels to acetylcholine. The present results suggest that several mechanisms may be involved in the inhibition of vascular tone by vasodilators.

Parathyroid hormone-related protein-(1-34) inhibits intrinsic pump activity of isolated murine lymph vessels

2001 ◽  
Vol 281 (1) ◽  
pp. H60-H66 ◽  
Author(s):  
Risuke Mizuno ◽  
Nobuyuki Ono ◽  
Toshio Ohhashi
Keyword(s):  
Parathyroid Hormone ◽  
Smooth Muscles ◽  
Related Protein ◽  
Vascular Smooth Muscles ◽  
Lymph Vessels ◽  
Parathyroid Hormone Related Protein ◽  
Low Concentrations ◽  
Pump Activity ◽  
Endogenous Nitric Oxide ◽  
High Concentrations

Parathyroid hormone-related protein (PTHrP) was originally found as a tumor-derived vasoactive factor and has also been known to produce significant relaxation of vascular smooth muscles. Thus effects of PTHrP-(1-34), a PTH receptor-binding domain, on spontaneous lymphatic pump activity was investigated in isolated pressurized lymph vessels of mice. Low concentrations (1 × 10−10 and 3 × 10−10 M) of PTHrP-(1-34) dilated lymph vessels and reduced the frequency of pump activity, whereas high concentrations (1 × 10−9 to 1 × 10−8 M) of PTHrP-(1-34) caused dilation with cessation of the lymphatic pump activity. N ω-nitro-l-arginine methyl ester (l-NAME; 3 × 10−5 M) but not indomethacin (1 × 10−5 M) significantly reduced the PTHrP-(1-34)-induced inhibitory responses of the lymphatic pump activity. In the presence of l-NAME (3 × 10−5 M) and l-arginine (1 × 10−3 M), the l-NAME-induced inhibition in the PTHrP-(1-34)-mediated responses was significantly reduced. Glibenclamide (1 × 10−6 M) significantly suppressed the inhibitory responses of the lymphatic pump activity induced by PTHrP-(1-34) and S-nitroso- N-acetyl-penicillamine. The PTHrP-(1-34)-mediated inhibitory responses were significantly reduced by treatment with PTHrP-(7-34) (1 × 10−7 M). These results suggest that PTHrP-(1-34) inhibits spontaneous pump activity of the isolated lymph vessels via PTH receptors and that production and release of endogenous nitric oxide and activation of ATP-sensitive K+ channels in the lymph vessels contribute to the PTHrP-(1-34)-mediated inhibitory responses of the lymphatic pump activity.

Mechanisms of endothelial cell activation by endocannabinoid 2-arachidonoylglycerol

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Jehle ◽  
L Eich ◽  
E Avraamidou ◽  
V Tiyerili ◽  
L Bindila ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Endothelial Cell ◽  
Coronary Artery ◽  
Carotid Artery ◽  
Adhesion Molecules ◽  
Common Carotid Artery ◽  
Endothelial Repair ◽  
The Common ◽  
Artery Disease

Abstract Background Endothelial dysfunction promotes atherogenesis, vascular inflammation, and thrombus formation. Reendothelialization after angioplasty is required in order to restore vascular function and to prevent stent thrombosis. The endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) is a known modulator of inflammation. Earlier studies have demonstrated the relevance of this endocannabinoid in human pathophysiology during coronary artery disease and in murine experimental atherogenesis. However, evidence on the impact of 2-AG on endothelial cell function remains scarce. Methods Endothelial repair was studied in two treatment groups of wildtype mice following electrical denudation of the common carotid artery. One group received the monoacylglycerol lipase (MAGL)-inhibitor JZL184, which impairs 2-AG degradation and thus causes elevated 2-AG levels, the other group received DMSO. The residual endothelial gap at five days was visualized by Evan's blue staining in either group. In vitro, the effect of 2-AG on human coronary artery endothelial cell (HCAEC) viability was assessed by an XTT-based assay. Endothelial activation was studied by an adhesion assay of THP-1 monocytes to 2-AG-preconditioned HCAEC. Activation of HCAEC adhesion molecules was characterized by flow cytometry. Results Elevated 2-AG levels significantly impaired reendothelialization in wildtype mice following electrical injury of the common carotid artery, resulting in a residual denudation at 5 days of 2291±286 μm vs. 1505±223 μm (n=18–19; p<0.05). In vitro, 2-AG significantly reduced viability of HCAEC at 24 hours (0.31±0.10 vs. 1.00±0.08; n=3; p<0.01). Finally, 2-AG promoted HCAEC activation resulting in a significant increase in THP-1 monocyte adhesion to HCAEC following pre-treatment of HCAEC with 2-AG (0.17±0.03 THP-1 cells per HCAEC vs. 0.07±0.01 THP-1 cells per HCAEC; n=3; p<0.05). Adhesion molecules E-selectin, ICAM-1 and VCAM-1, that are known to be regulated by 2-AG in the venous endothelium, remained unchanged in arterial endothelial cells. Besides, HCAEC migration, ROS-production, expression of NADPH oxidases and secretion of inflammatory cytokines were unaffected by 2-AG. Conclusion Elevated 2-AG levels hamper endothelial repair and impair HCAEC proliferation while facilitating adhesion of monocytes. Intriguingly, the underlying mechanisms in the arterial vascular bed appear distinct from venous endothelium. Given that 2-AG is elevated during coronary artery disease in humans, 2-AG might impair reendothelialization after angioplasty and thus impact on clinical outcomes. Funding Acknowledgement Type of funding source: None

P7142-AG impacts on endothelial cell activation and endothelial cell viability in vitro and impairs endothelial repair in vivo

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Jehle ◽  
M Danisch ◽  
S Bagheri ◽  
E Avraamidou ◽  
V Tiyerili ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Carotid Artery ◽  
Inflammatory Cytokines ◽  
Common Carotid Artery ◽  
Myeloid Cells ◽  
Ros Production ◽  
Nadph Oxidases ◽  
Endothelial Repair ◽  
The Common

Abstract Background The endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) is a known modulator of inflammation and few studies have addressed its influence on myeloid cells in the context of atherogenesis. However, the impact of 2-AG on endothelial cell function has not been studied before. Methods Endothelial repair was studied in two treatment groups of wildtype mice following electrical denudation of the common carotid artery at a length of 3000 μm. One group received the monoacylglycerol lipase (MAGL)-inhibitor JZL184 [5 mg/kg i.p.], which impairs 2-AG degradation and thus causes elevated 2-AG levels, the other group received vehicle. The residual endothelial gap at five days in either group was visualized by Evan's blue staining. In vitro, the effect of 2-AG on human coronary artery endothelial cell (HCAEC) viability was assessed by an XTT-based assay. Endothelial activation was studied by an adhesion assay of THP-1 monocytes to 2-AG-preconditioned HCAEC. HCAEC migration, ROS-production, expression of NADPH oxidases, and secretion of inflammatory cytokines were assessed by Boyden chamber, qPCR, and colorimetric assays. Results Treatment with JZL184 produced a significant increase in 2-AG levels and impaired reendothelialisation in wildtype mice following electrical injury of the common carotid artery. The residual denudation at 5 days yielded 2291±286 μm in JZL184-treated animals vs. 1505±223 μm in vehicle treated controls (n=18–19; p<0.05). In vitro, JZL184 significantly reduced viability of HCAEC at 24 hours (0.31±0.10 vs. 1.00±0.08; n=3; p<0.01). Finally, 2-AG promoted HCAEC activation resulting in a significant increase in THP-1 monocyte adhesion to HCAEC following pre-treatment of HCAEC with 2-AG (0.17±0.03 THP-1 cells per HCAEC vs. 0.07±0.01 THP-1 cells per HCAEC; n=3; p<0.05). Besides, HCAEC migration, ROS-production, expression of NADPH oxidases and secretion of inflammatory cytokines were unaffected by 2-AG. Conclusion Elevated 2-AG levels appear to hamper endothelial repair and to promote HCAEC activation and cell death. Our data suggest that besides its influence on myeloid cells, 2-AG is also adverse to endothelial integrity which might promote early atherosclerotic lesion formation. Thus, decreasing vascular 2-AG levels might represent a promising therapeutic strategy for the prevention of atherosclerosis and coronary heart disease.

Structure–activity study of kinins in vascular smooth muscles

1981 ◽  
Vol 59 (4) ◽  
pp. 380-389 ◽  
Author(s):  
P. Gaudreau ◽  
J. Barabé ◽  
S. St-Pierre ◽  
D. Regoli
Keyword(s):  
Carotid Artery ◽  
Terminal Ileum ◽  
Common Carotid Artery ◽  
Solid Phase ◽  
Biological Activities ◽  
Gel Filtration ◽  
Smooth Muscles ◽  
Exchange Chromatography ◽  
Phase Method ◽  
Vascular Smooth Muscles

To explore further the relations between the chemical structure and the biological activities of kinins, a series of bradykinin fragments and analogues was prepared by the solid-phase method. Bradykinin and kallidin were also extended at the C- or the N-terminai end by the addition of one or more residues in order to evaluate the importance of peptide chain length and of additional positive charges at the N-terminal end for the biological activity. After purification by cation-exchange chromatography and gel filtration, the compounds were characterized by thin-layer chromatography, paper electrophoresis, elemental analyses, and amino acid analyses. All compounds were tested on three vascular preparations (the dog common carotid artery, the rabbit jugular vein, and the guinea pig anterior mesenteric vein) in order to measure their relative potencies as relaxant (on the dog common carotid artery) or as stimulant (the two veins) of vascular smooth muscles. The compounds were also tested on the cat terminal ileum and the rabbit aorta for comparison.The results reported in this paper indicate that all the new analogues of bradykinin as well as some fragments and analogues described before by us and by other workers are full agonists in the three vascular preparations. No partial agonists or antagonists have been identified. The order of potency of the various kinin analogues is similar in the three vascular preparations and follows the same pattern as that found in the cat terminal ileum. It is therefore concluded that (a) the three vascular preparations utilized in the present experiment possess a B2 receptor type that appears to be similar to that of the cat terminal ileum and of the rat uterus described before and (b) receptors of the B2 type are able to mediate both the inhibitory and the excitatory actions of kinins in vascular smooth muscles.

An in vitro porcine model evaluating a novel stent retriever for thrombectomy of the common carotid artery

2015 ◽  
Vol 87 (3) ◽  
pp. 457-464 ◽  
Author(s):  
Yongjun Jiang ◽  
Yun Li ◽  
Xiaomeng Xu ◽  
Yongyi Yu ◽  
Wenhua Liu ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Common Carotid Artery ◽  
Porcine Model ◽  
Stent Retriever ◽  
The Common

In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
Author(s):  
Margaret L Rand ◽  
Peter L Gross ◽  
Donna M Jakowec ◽  
Marian A Packham ◽  
J Fraser Mustard
Keyword(s):  
Cyclic Amp ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Rabbit Platelets ◽  
High Concentrations ◽  
In Vitro Effects ◽  
Aggregation Of Platelets

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.

Aggregation of Cat Platelets in Vitro

1970 ◽  
Vol 23 (03) ◽  
pp. 601-620 ◽  
Author(s):  
Th. B Tschopp
Keyword(s):  
Adenosine Monophosphate ◽  
Blood Collection ◽  
Base Line ◽  
Reversible Aggregation ◽  
Low Concentrations ◽  
Irreversible Aggregation ◽  
High Concentrations ◽  
Two Phases ◽  
Improved Technique

SummaryAggregation of cat platelets in the citrated plasma is examined by means of Born’s absorptiometer. A marked tendency of the platelets of this species to spontaneous aggregation necessitated first of all the development of an improved technique of blood collection.A hypothesis according to which 5-HT is released from the platelets, explains the absence of oscillations on the base line of the absorptiometer, the absence of platelet swelling, when ADP is added, and the effect of stirring on the aggregation curves in cat PRP. The average volume of cat platelets amounts to 10.46 μ3 when directly fixed in the blood, when fixed from PRP to 12.17 μ3, when fixed from stirred PRP to 13.51 μ3.In low concentrations (0.3-2 μM) ADP produce reversible aggregation; in narrowly restricted, individually dissimilar mean concentrations irreversible aggregation in two phases and in high concentrations, irreversible aggregation in one phase. Like ADP serotonin produces 2 phase irreversible aggregation in concentrations of 3-10 μM, but unlike ADP, the aggregation velocity decreases again with high 5-HT concentrations (>100 μM). Adrenaline does not produce aggregation and it is likely that adenosine and adenosine monophosphate inhibit the aggregation by serotonin but not by ADP. Species differences in the aggregation of human, rabbit and cat platelets are discussed.

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