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.

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.

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.

Inflammation induced changes in arachidonic acid metabolism in cat LES circular muscle

2005 ◽  
Vol 288 (4) ◽  
pp. G787-G797 ◽  
Author(s):  
Ling Cheng ◽  
Weibiao Cao ◽  
Jose Behar ◽  
Piero Biancani ◽  
Karen M. Harnett
Keyword(s):  
Arachidonic Acid ◽  
Circular Muscle ◽  
Arachidonic Acid Metabolism ◽  
Acid Metabolites ◽  
Esophageal Sphincter ◽  
Cat Model ◽  
Induced Changes

Myogenic lower esophageal sphincter (LES) tone is maintained by arachidonic acid metabolites, such as PGF2α and thromboxane A2/B2. Experimental esophagitis in cat reduces LES in vivo pressure and in vitro tone. Because IL-1β may mediate esophagitis-associated reduction in ACh release in esophagus, we examined whether IL-1β may also play a role in esophagitis-induced reduction of LES tone. A cat model of experimental esophagitis was obtained by repeated esophageal perfusion with HCl (Biancani P, Barwick K, Selling J, and McCallum R. Gastreonterology 87: 8–16, 1984 and Sohn UD, Harnett KM, Cao W, Rich H, Kim N, Behar J, and Biancani P. J Pharmacol Exp Ther 283: 1293–1304, 1997.). LES circular muscle strips were examined in muscle chambers as previously described (Biancani P, Billett G, Hillemeier C, Nissenshon M, Rhim BY, Sweczack S, and Behar J. Gastroenterology 103: 1199–1206, 1992). Levels of inflammatory mediators were measured. IL-1β levels were higher in esophagitis than in normal LES. IL-1β reduced normal LES tone, and the reduction was reversed by catalase, suggesting a role of H2O2. This was confirmed by IL-1β-induced production of H2O2 in normal LES and elevated H2O2 levels in esophagitis. H2O2 by itself is sufficient to explain the changes that occur in the muscle, reducing its ability to contract. H2O2 increased PGE2 in normal LES, and PGE2 levels were elevated in esophagitis LES, whereas PGF2α levels were unchanged. H2O2 also increased levels of 8-isoprostanes, stable prostaglandin-like compounds formed by free radical-induced peroxidation of arachidonic acid, and 8-isoprostane levels were elevated in esophagitis. The PGF2α analog 8-iso-PGF2α caused little contraction of LES strips but reduced PGF2α binding and contraction of normal LES. In esophagitis, PGF2α binding and contraction were reduced in LES, suggesting that isoprostanes may contribute to reduction in tone in esophagitis. The data suggest that, in esophagitis, IL-1β causes production of H2O2. H2O2 increases PGE2, which relaxes the LES, and 8-iso-F2α, which blocks PGF2α-mediated contraction.

Testosterone Potentiation of Ionophore and ADP Induced Platelet Aggregation : Relationship to Arachidonic Acid Metabolism

1981 ◽  
Vol 46 (02) ◽  
pp. 538-542 ◽  
Author(s):  
R Pilo ◽  
D Aharony ◽  
A Raz
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Unsaturated Fatty Acids ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Arachidonic Acid Metabolism ◽  
Ionophore A23187 ◽  
Low Concentrations ◽  
Induced Aggregation

SummaryThe role of arachidonic acid oxygenated products in human platelet aggregation induced by the ionophore A23187 was investigated. The ionophore produced an increased release of both saturated and unsaturated fatty acids and a concomitant increased formation of TxA2 and other arachidonate products. TxA2 (and possibly other cyclo oxygenase products) appears to have a significant role in ionophore-induced aggregation only when low concentrations (<1 μM) of the ionophore are employed.Testosterone added to rat or human platelet-rich plasma (PRP) was shown previously to potentiate platelet aggregation induced by ADP, adrenaline, collagen and arachidonic acid (1, 2). We show that testosterone also potentiates ionophore induced aggregation in washed platelets and in PRP. This potentiation was dose and time dependent and resulted from increased lipolysis and concomitant generation of TxA2 and other prostaglandin products. The testosterone potentiating effect was abolished by preincubation of the platelets with indomethacin.

Role of NO in Flow-Induced Remodeling of the Rabbit Common Carotid Artery

1996 ◽  
Vol 16 (10) ◽  
pp. 1256-1262 ◽  
Author(s):  
François Tronc ◽  
Michel Wassef ◽  
Bruno Esposito ◽  
Daniel Henrion ◽  
Seymour Glagov ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Common Carotid Artery

scholarly journals The role of the arachidonic acid cascade in the hypotensive activity of N-(dibenzyloxyphosphinoyl)-L-alanyl-L-prolyl-L-proline

1986 ◽  
Vol 40 ◽  
pp. 233
Author(s):  
Ryota Yoshimoto ◽  
Toshihiko Ishimitsu ◽  
Yoshikatsu Koyama ◽  
Shigebumi Hashimoto ◽  
Hiroaki Matsuoka ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Hypotensive Activity ◽  
Arachidonic Acid Cascade
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