Contraction Of Rat Basilar Artery Research Articles

EndothelinA–endothelinB receptor cross-talk in rat basilar artery in situ

The rationale for the therapeutic use of dual as opposed to selective endothelin (ET) receptor antagonists stems in part from cross-talk between the ET(A) and ET(B) receptors. However, whether ET(A)-ET(B) receptor cross-talk is present in the cerebral vasculature is difficult to discern since findings of cross-talk contrast even among the few reports available. Thus, this study tested whether ET(A)-ET(B) receptor cross-talk is present in the rat basilar artery. In an in situ cranial window, 0.1μM sarafotoxin S6c, an ET(B) receptor agonist, relaxed basilar artery basal tone by 54%. ET-1 (3nM) in the absence and presence of 10μM BQ123, an ET(A) receptor agonist, induced 13% contraction and 15% relaxation, respectively. In contrast, the 3-nM ET-1 plateau contraction was relaxed by only ∼50% by 3-10μM BQ123 and 10μM BQ610, ET(A) receptor antagonists. N(ω)-nitro-L: -arginine, an NO synthase inhibitor, did not enhance contraction to 3nM ET-1, suggesting that the partial relaxation of the ET-1 plateau contraction did not involve unmasked endothelial ET(B) receptor-mediated relaxation. The ∼50% ET-1 contraction that remained following ET(A) receptor antagonist was relaxed by 3-10μM BQ788, consistent with an ET(B) receptor-mediated component of contraction. However, 10μM BQ788 in the absence of prior ET(A) receptor antagonist did not cause relaxation. Subsequent BQ123 addition in the presence of BQ788 completely relaxed the ET-1 contraction. PD145065 (1μM), an ET(A/B) receptor antagonist, completely relaxed 3-nM ET-1 contracted vessels in both the absence and presence of BQ123. These findings suggest that the inability of ET(A) receptor antagonist to completely relax the ET-1 plateau contraction in rat basilar artery is due to ET(A)-ET(B) receptor cross-talk.

Mitochondrial monoamine oxidase‐A‐mediated hydrogen peroxide generation enhances 5‐hydroxytryptamine‐induced contraction of rat basilar artery

We evaluated the role(s) of monoamine oxidase (MAO)-mediated H₂O₂ generation on 5-hydroxytryptamine (5-HT)-induced tension development of isolated basilar artery of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Basilar artery (endothelium-denuded) was isolated for tension measurement and Western blots. Enzymically dissociated single myocytes from basilar arteries were used for patch-clamp electrophysiological and confocal microscopic studies. Under resting tension, 5-HT elicited a concentration-dependent tension development with a greater sensitivity (with unchanged maximum tension development) in SHR compared with WKY (EC(50) : 28.4 ± 4.1 nM vs. 98.2 ± 9.4 nM). The exaggerated component of 5-HT-induced tension development in SHR was eradicated by polyethylene glycol-catalase, clorgyline and citalopram whereas exogenously applied H₂O₂ enhanced the 5-HT-elicited tension development in WKY. A greater protein expression of MAO-A was detected in basilar arteries from SHR than in those from WKY. In single myocytes and the entire basilar artery, 5-HT generated (clorgyline-sensitive) a greater amount of H₂O₂ in SHR compared with WKY. Whole-cell iberiotoxin-sensitive Ca(2+) -activated K(+) (BK(Ca) ) amplitude measured in myocytes of SHR was approximately threefold greater than that in WKY (at +60 mV: 7.61 ± 0.89 pA·pF(-1) vs. 2.61 ± 0.66 pA·pF(-1) ). In SHR myocytes, 5-HT caused a greater inhibition (clorgyline-, polyethylene glycol-catalase- and reduced glutathione-sensitive) of BK(Ca) amplitude than in those from WKY. 5-HT caused an increased generation of mitochondrial H₂O₂ via MAO-A-mediated 5-HT metabolism, which caused a greater inhibition of BK(Ca) gating in basilar artery myocytes, leading to exaggerated basilar artery tension development in SHR.

The importance of extracellular calcium for endothelin type A and B receptor-mediated contraction in rat basilar artery

The importance of extracellular calcium for endothelin type A and B receptor-mediated contraction in rat basilar artery

Adenovirus-mediated heme oxygenase-1 gene transfection prevents hemoglobin-induced contraction of rat basilar artery.

Vasospasm is a consequence of erythrocyte lysis in the subarachnoid space that releases hemoglobin and possibly other spasmogenic substances. Removing the blood clot early after SAH, either surgically or by intracisternal fibrinolysis with tissue plasminogen activator or urokinase, may prevent vasospasm [1]. In view of the critical role that hemoglobin appears to play in the pathogenesis of vasospasm, modification of the metabolism of hemoglobin and heme may be im- portant to preventing vasospasm. Oxidation of ferrous iron in oxy- or deoxyhemoglobin produces meth- emoglobin that more readily releases its heme groups from the globin chains. Globin chains probably are degraded by intra- and extracellular proteases. The heme group is metabolized to biliverdin, carbon mon- oxide (CO) and iron by heme oxygenases (HO) that consist of at least 3 isozymes including the oxidative stress-inducible protein HO-1 [2].

O-40 - Nicotine-induced endothelium-dependent contraction in rat basilar artery: involvement of leukotriene B4 and reactive oxygen species

O-40 - Nicotine-induced endothelium-dependent contraction in rat basilar artery: involvement of leukotriene B4 and reactive oxygen species

Effects of alniditan on neurogenic oedema in the rat dura mater and on contraction of rat basilar artery

The non-indole 5-HT receptor agonist, alniditan (R 91274), was tested and compared to sumatriptan in an in vivo model of neurogenic inflammation within the meninges of rats and in rat basilar artery in a Mulvany–Halpern chamber in vitro. Alniditan dose dependently attenuated the neurogenic inflammation and was more potent than sumatriptan. The alniditan response was blocked by the 5-HT 1B/D receptor antagonist, GR 127935 (2′-methyl-4′-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-carboxylic acid [4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-amide), but not by ketanserin, indicating that the effect is mediated through 5-HT 1B/D receptors. Alniditan did not attenuate substance P-induced inflammation, suggesting that the mediating receptors are located prejunctionally. In vitro alniditan exhibited less vasoconstrictive effects on the rat basilar artery than did sumatriptan, although at a very high concentration (1 mM), alniditan caused intensive constriction, most likely through a mechanism independent from 5-HT receptor activation.

Evidence that 5-HT 2 receptors predominantly mediate the contraction of the rat basilar artery to 5-hydroxytryptamine

We characterised the 5-hydroxytryptamine (5-HT) receptor subtype which mediates the contraction of the rat isolated basilar artery, mounted in a myograph, by using agonists and antagonists for 5-HT 1-like, 5-HT 2, 5-HT 3 AND 5-HT 4, receptors. The rank order of potency for a range of selective agonists was: 5-HT > α-mcthyl-5-HT > 5-carboxamidotryptamine > 2-methyl-5-HT > sumatriptan. The maximum contractions for these agonists (E max) was less than for 5-HT while 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was devoid of contractile activity. Ketanserin antagonised the contractile effect of 5-HT in the rat basilar artery with a provisional pA 2 estimate of 9.3 ± 0.2. A similar antagonism was observed against α-methyl-5-HT. Ergometrine (0.01–1 μM) was devoid of any agonist activity but antagonised the contractile effect of 5-HT on the rat basilar artery with a provisional pK B of 8.7 (7.8–9.8, 95% confidence limits). The 5-HT 3 and 5-HT 4 receptor antagonist ICS 20593(1 (10 μM) did not alter the response to 5-HT. The high potency and efficacy of α-methyl-5-HT, poor effect of sumatriptan and antagonism of 5-HT by ergometrinc and ketanscrin, support the conclusion that the 5-HT 2, receptors are primarily responsible for the 5-HT-induccd contraction of rat basilar artery.