Possible Role of Endothelial Thromboxane A2 in the Resting Tone and Contractile Responses to Acetylcholine and Arachidonic Acid in Canine Cerebral Arteries

Shirahase, Hiroaki; Usui, Hachiro; Kurahashi, Kazuyoshi; Fujiwara, Motohatsu; Fukui, Kiyoshi

doi:10.1097/00005344-198711000-00004

Cited by 84 publications

(42 citation statements)

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“…In some preparations, the endotheli um was disrupted mechanically by gentle ablation of the luminal surface with a small steel spatula. Denudation of the endothelium was confirmed pharmacologically by the disappearance of the 10-6 M ACh-induced relaxation together with the preservation of the 10-7 M nitroprus side sodium-induced relaxation or ascertained morpho logically as described in our previous report (16).…”

Section: Animals and Dietsmentioning

confidence: 77%

Effects of SM-9018, a Potential Atypical Neuroleptic, on the Central Monoaminergic System in Rats

Kitagawa

Yamaguchi

Kunitomo

et al. 1993

Japanese Journal of Pharmacology

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ABSTRACT-This investigation was undertaken to characterize the vasoconstrictor responsiveness in aortas isolated from a rat model of arteriosclerosis induced by vitamin D2 (VD) administration followed by feeding with a high-cholesterol diet. Cumulative contractile responses to KC1, noradrenaline and serotonin in thoracic aortic strips isolated from arteriosclerotic rats were slightly augmented in concentrations lower than the EC50 value of each agent and rather attenuated in their higher concentrations as compared with those from normal rats. Maximum contractions to the agonists were markedly attenuated in arteriosclerotic aortas; the degree of attenuation was greater in rats treated with a combination of VD and cholesterol than in those treated with VD alone. There was a significant negative correlation between the maximum contrac tion to KCI, noradrenaline or serotonin and the content of calcium or cholesterol ester in aortas. Removal of endothelium markedly enhanced sensitivity and contractility to the agonists in aortic strips from normal rats, whereas the same procedure only slightly enhanced them in aortic strips from arteriosclerotic rats. These results indicate that in arteriosclerotic rat aortas, contractile responsiveness to agonists of vascular smooth muscle cells is impaired with deposition of calcium and cholesterol, and they suggest that augmenta tion of contractile responses to the agonists in lower concentrations is due to impairment of endothelial func tion.Keywords: Arteriosclerosis, Vitamin D, High-cholesterol diet, Calcification, Contractile response Atherosclerosis accompanied with hypercholesterol emia results in altered responsiveness of blood vessels to vasoactive substances in parallel with smooth muscle cell proliferation and lipid deposition. A number of studies have shown augmented responses to serotonin, histamine or ergonovine (1-6), and impaired endothelium-depend ent relaxation to a variety of vasodilator agents (7 -12) in various regions of arteries with experimental or human atherosclerosis. These changes may predispose athero sclerotic arteries to vasospasm. On the other hand, only a limited number of studies have been carried out on the vascular reactivity of arteriosclerotic vessels without depo sition of lipids (13,14). Henrion et al. (14) have reported that in the aorta from a rat model of vascular calcium overload produced by treatment with vitamin D3 and nicotine, not only endothelium-dependent relaxation to carbachol but also the vasoconstrictive response to noradrenaline is attenuated, while the relaxing responses to sodium nitroprusside is unchanged. Studies in our laboratory have also shown attenuation of vasorelaxation to acetylcholine or the calcium ionophore A23187 in aortas from rats with arteriosclerosis produced by four consecutive doses of vitamin D2 (VD) (15). We also dem onstrated that such impairment of endothelium-depend ent relaxations to acetylcholine and A23187 was propor tional to the degree of calcium deposition and facilitated by cholesterol feeding ...

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Section: Animals and Dietsmentioning

confidence: 77%

Effects of SM-9018, a Potential Atypical Neuroleptic, on the Central Monoaminergic System in Rats

Kitagawa

Yamaguchi

Kunitomo

et al. 1993

Japanese Journal of Pharmacology

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“…We have reported that EDCF released by various substances is probably TXA2 in canine cerebral arteries (Usui et al, 1983;Shirahase et al, 1987;1988a,b;Manabe et al, 1989). In rabbit pulmonary arteries, ACh causes an EDC via production of TXA2 (Altiere et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

“…In most of the peripheral arteries from various species, endothelium-dependent relaxation (EDR) has been predominantly observed and considered to be more important than endothelium-dependent contraction (EDC). In canine cerebral arteries, various vasoactive substances including acetylcholine (ACh), Ca2+ ionophore and adenine nucleotides cause EDC while they evoke EDR in peripheral arteries (Usui et al, 1983;Shirahase et al, 1987;1988a,b). Vasoactive peptides such as angiotensin II, endothelin-1 and somatostatin also induce EDC in cerebral arteries (Manabe et al, 1989;Shirahase et al, 1991;.…”

Section: Introductionmentioning

confidence: 99%

Endothelium‐dependent contraction in intrapulmonary arteries: mediation by endothelial NK₁ receptors and TXA₂

Shirahase

Kanda

Kurahashi

et al. 1995

British J Pharmacology

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1 We have examined whether three natural tachykinins, substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) induce an endothelium-dependent contraction (EDC) in the rabbit isolated intrapulmonary artery.2 Removal of the endothelium almost abolished the contraction induced by SP (10' M) while it did not attenuate the contraction induced by SP (lI-V M), NKA (0 -l10-7 M) or NKB (10' and 10 M). 3 The EDC induced by SP (10' M) was abolished by NKI antagonists (FK-888, and SR-140333) but not by an NK2 antagonist (SR-48968). 4 The EDC induced by SP was attenuated by cyclo-oxygenase inhibitors (aspirin and indomethacin), thromboxane A2 (TXA2) synthetase inhibitors (OKY-046, KY-234 and KY-063) and a TXA2 antagonist (S-1452). 5 The rank order of potency causing endothelium-independent contraction (EIC) was NKA > NKB> SP. The EIC induced by SP (1O' M) was attenuated by an NK2 antagonist but not by NK, antagonists, cyclo-oxygenase inhibitors, TXA2 synthetase inhibitors or a TXA2 antagonist. 6 In conclusion, SP at 101 M induces EDC via endothelial NK, receptors and TXA2 production, and SP at 10-7 M induces EIC via NK2 receptors in the rabbit intrapulmonary artery.

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“…The exact nature of endothelium-derived contracting factor(s) remains controversial. Possible candidates include superoxide anions (Vanhoutte & Katusic, 1988), thromboxane A2 (Shirahase et al, 1987), and endothelin (Yanagisawa et al, 1988) (Figure 4). …”

Section: Endothelial Cells Endothelium-derived Contracting Factorsmentioning

confidence: 99%

Why are converting enzyme inhibitors vasodilators?

Vanhoutte

Auch-Schwelk

Biondi

et al. 1989

Brit J Clinical Pharma

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1. The primary action of the converting enzyme inhibitors to prevent the formation of angiotensin II can explain a decrease in peripheral vascular resistance in patients with elevated, but not in those with normal or reduced plasma renin levels. 2. The inhibition of the breakdown of bradykinin will potentiate the vasodilator properties of the endogenously produced peptide. These include direct relaxation of certain vascular smooth muscle, production of vasodilator prostanoids and release of endothelium‐derived relaxing factor(s). The greater release of the latter in the kidney could exert a negative feedback on the release of renin. 3. In addition, converting enzyme inhibitors may directly (by a prejunctional effect) and indirectly (by curtailing the production of angiotensin II) reduce the release of noradrenaline in the blood vessel wall. 4. Converting enzyme inhibitors may also directly reduce the responsiveness of vascular smooth muscle to vasoconstrictor stimuli (e.g. alpha‐adrenoceptor activation). 5. The different effects of these therapeutic agents may concur to induce peripheral vasodilatation.

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Possible Role of Endothelial Thromboxane A2 in the Resting Tone and Contractile Responses to Acetylcholine and Arachidonic Acid in Canine Cerebral Arteries

Cited by 84 publications

References 0 publications

Effects of SM-9018, a Potential Atypical Neuroleptic, on the Central Monoaminergic System in Rats

Effects of SM-9018, a Potential Atypical Neuroleptic, on the Central Monoaminergic System in Rats

Endothelium‐dependent contraction in intrapulmonary arteries: mediation by endothelial NK₁ receptors and TXA₂

Why are converting enzyme inhibitors vasodilators?

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Possible Role of Endothelial Thromboxane A2 in the Resting Tone and Contractile Responses to Acetylcholine and Arachidonic Acid in Canine Cerebral Arteries

Cited by 84 publications

References 0 publications

Effects of SM-9018, a Potential Atypical Neuroleptic, on the Central Monoaminergic System in Rats

Effects of SM-9018, a Potential Atypical Neuroleptic, on the Central Monoaminergic System in Rats

Endothelium‐dependent contraction in intrapulmonary arteries: mediation by endothelial NK1 receptors and TXA2

Why are converting enzyme inhibitors vasodilators?

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Endothelium‐dependent contraction in intrapulmonary arteries: mediation by endothelial NK₁ receptors and TXA₂