Anti-Spasmogenic Effects of Bencianol (ZY15051 on Human Cerebral Arteries In Vitro

Cephalalgia ◽  
1985 ◽  
Vol 5 (4) ◽  
pp. 217-221 ◽  
Author(s):  
ET Whalley ◽  
KS Paul ◽  
OP Gulati
Keyword(s):  
Angiotensin Ii ◽  
Guinea Pig ◽  
Cerebral Arteries ◽  
Arterial Spasm ◽  
Wide Range ◽  
Prostaglandin F ◽  
Basilar Arteries

Experiments were performed to assess the ability of bencianol (ZY15051) to reverse contractions of human basilar arteries in vitro that were induced by a wide range of substances implicated in the aetiology of migraine and cerebral arterial spasm. Bencianol caused a dose-related (1–100 μg ml-1) reversal of contractions induced by 5-hydroxytryptamine, nor-adrenaline, angiotensin II, prostaglandin F2a, and U-46619 (a thromboxane-A2 mimetic). Bencianol was more effective against contractions induced by EC50 compared to maximal concentrations of each agent, and was least effective against the thromboxane-A2 mimetic, U-46619. In addition, contractions induced by thromboxane-A2-like substances generated from guinea-pig lungs were also reversed by bencianol but only at the highest concentration used (100 mg ml-1). The relevance of this action of bencianol to migraine and cerebral arterial spasm is discussed.

Prostacyclin and cerebral vessel relaxation

1982 ◽  
Vol 57 (3) ◽  
pp. 334-340 ◽  
Author(s):  
Kamal S. Paul ◽  
Eric T. Whalley ◽  
Christine Forster ◽  
Richard Lye ◽  
John Dutton
Keyword(s):  
Angiotensin Ii ◽  
Arterial Spasm ◽  
Cerebral Vessel ◽  
Content Type ◽  
Wide Range ◽  
Potent Vasodilator ◽  
Dose Dependent Fashion ◽  
Basilar Arteries ◽  
High Concentrations

✓ The authors have studied the ability of prostacyclin to reverse contractions of human basilar arteries in vitro that were induced by a wide range of substances implicated in the etiology of cerebral arterial spasm. Prostacyclin (10−10 to 10−6M) caused a dose-related reversal of contractions induced by 5-hydroxytryptamine, noradrenaline, angiotensin II, prostaglandin (PG)F2α, and U-46619 (a thromboxane-A2 mimetic). These agents were tested at concentrations or volumes that produced almost maximum or maximum responses and those that produced approximately 50% of the maximum response. Contractions induced by maximum concentrations of angiotensin II and U-46619 were least affected by prostacyclin. In addition, contractions induced by thromboxane-A2 generated from guinea-pig lung were reversed in a dose-dependent fashion by prostacyclin. This ability of prostacyclin to physiologically antagonize contractions of the human basilar artery in vitro induced by high concentrations of various spasmogenic agents suggests that such a potent vasodilator agent or more stable analogue may be of value in the treatment of such disorders as cerebral arterial spasm following subarachnoid hemorrhage.

scholarly journals in vitro Effects of Calcium Antagonists PN 200-110, Nifedipine, and Nimodipine on Human and Canine Cerebral Arteries

1983 ◽  
Vol 3 (3) ◽  
pp. 354-361 ◽  
Author(s):  
E. Müller-Schweinitzer ◽  
P. Neumann
Keyword(s):  
Rank Order ◽  
Cerebral Arteries ◽  
Isometric Tension ◽  
Mesenteric Arteries ◽  
Organ Bath ◽  
Vasoconstrictor Response ◽  
Dihydropyridine Derivative ◽  
Basilar Arteries ◽  
In Vitro Effects

PN 200–110 [4-(2, 1, 3-benzoxadiazol - 4 -) - 1,4-dihydro - 2,6 - dimethyl - pyridine - 3,5 - dicarboxylic acid methyl 1-methylethyl ester], a new dihydropyridine derivative, was investigated by recording isometric tension on spiral strips from human and canine arteries in tissue baths at 37°C. Responses to increasing concentrations of CaCl2 were investigated in calcium-free depolarizing solution (60 mmol/L KCl in equimolar replacement for NaCl, 50 mmol/L TRIZMA buffer, pH 7.4). Comparison of those concentrations that reduced the vasoconstrictor response to 1.6 mmol/L CaCl2 by 50% revealed the following order of potencies on both human and canine arteries: PN 200–110 > nimodipine > nifedipine. Responses to 5-hydroxytryptamine (5-HT) and blood were investigated in Krebs–Henseleit solution (NaHCO3 buffer). On canine arteries, PN 200–110 antagonized responses to 5-HT when used at 10–30 pmol/L; it was ∼70 times more potent on basilar than on mesenteric arteries, whereas both nifedipine and nimodipine were, respectively, ∼10 and 6 times more potent on basilar than on mesenteric arteries. When canine basilar arteries were constricted by the addition of blood to the organ bath, each of the investigated dihydropyridine derivatives elicited concentration-dependent relaxation, producing the following order of potencies: PN 200–110 > nifedipine = nimodipine. On human anterior cerebral arteries, the blood-induced contractions were counteracted in the following rank order: PN 200–110 = nimodipine > nifedipine. The results suggest that due to its potent calcium-blocking activity on cerebral arteries, PN 200–110 might be of value for the prevention and treatment of cerebrovascular spasms following subarachnoid hemorrhage.

scholarly journals Nerve Fibers Containing Neuropeptide Y in the Cerebrovascular Bed: Immunocytochemistry, Radioimmunoassay, and Vasomotor Effects

1987 ◽  
Vol 7 (1) ◽  
pp. 45-57 ◽  
Author(s):  
L. Edvinsson ◽  
J. R. Copeland ◽  
P. C. Emson ◽  
J. McCulloch ◽  
R. Uddman
Keyword(s):  
Neuropeptide Y ◽  
Blood Vessels ◽  
Superior Cervical Ganglion ◽  
Cerebral Arteries ◽  
Nerve Fibers ◽  
Calcium Entry Blocker ◽  
Cervical Ganglion ◽  
Prostaglandin F ◽  
6 Hydroxydopamine

Perivascular nerve fibers containing neuropeptide Y (NPY)-like immunoreactivity were identified around cerebral blood vessels of human, cat, guinea pig, rat, and mouse. The major cerebral arteries were invested by dense plexuses; veins, small arteries, and arterioles were accompanied by few fibers. Removal of the superior cervical ganglion resulted in a reduction of NPY-like material in pial vessels and dura mater. Pretreatment with 6-hydroxydopamine or reserpine reduced the number of visible NPY fibers and the concentration of NPY in rat cerebral vessels. Sequential immuno-staining with antibodies toward dopamine-β-hydroxylase (DBH) (an enzyme involved in the synthesis of noradrenaline) and NPY revealed an identical localization of DBH and NPY in nerve cell bodies in the superior cervical ganglion and in perivascular fibers of pial blood vessels, suggesting their coexistence. Administration of NPY in vitro resulted in concentration-dependent contractions that were not modified by a sympathectomy. The contractions induced by noradrenaline, 5-hydroxytryptamine, and prostaglandin F2α and the dilator responses to calcitonin gene-related peptide were not modified by NPY in rat cerebral arteries. However, the constrictor response to NPY was reduced by 70% in the presence of the calcium entry blocker nifedipine, and abolished following incubation in a calcium-free buffer. These data suggest an interaction of NPY at a postsynaptic site, which for induction of contraction may open calcium channels in the sarcolemma of cerebral arteries.

Dose responses of cerebral arteries of the dog, rabbit, and man to human hemoglobin in vitro

1980 ◽  
Vol 53 (4) ◽  
pp. 486-490 ◽  
Author(s):  
Glyn R. Wellum ◽  
Thomas W. Irvine ◽  
Nicholas T. Zervas
Keyword(s):  
Cerebral Arteries ◽  
Postmortem Changes ◽  
Human Hemoglobin ◽  
Content Type ◽  
Weak Response ◽  
Basilar Arteries ◽  
Human Arteries ◽  
Dose Responses ◽  
Fine Print

✓ Dose responses in vitro of the basilar arteries of the dog, rabbit, and man to human hemoglobin are reported. For each species, the response occurred over a range of 10−9M to greater than 10−5M hemoglobin. When compared to a maximum serotonin contraction, the relative constriction induced by 10−5M hemoglobin was greater in the rabbit than in the dog, which in turn was greater than in man. The comparatively weak response of the human arteries is probably attributable to postmortem changes.

scholarly journals Actions of Platelet-Activating Factor on Isolated Feline and Human Cerebral Arteries

1990 ◽  
Vol 10 (3) ◽  
pp. 428-431 ◽  
Author(s):  
Tore K. Uski ◽  
Peter Reinstrup
Keyword(s):  
Receptor Antagonist ◽  
Cerebral Arteries ◽  
Platelet Activating Factor ◽  
Pial Arteries ◽  
Thromboxane Receptor ◽  
Prostanoid Production ◽  
Prostaglandin F ◽  
Basilar Arteries ◽  
Thromboxane Receptor Antagonist

The effects of platelet-activating factor (PAF) were studied on isolated feline basilar arteries (BAs) and human pial arteries (PAs). PAF contracted the BAs by 67% of the contraction induced by 124 m M K+ and the PAs by 80%. The contraction in BAs was unaffected by both indomethacin and the thromboxane receptor antagonist AH23848. PAF relaxed prostaglandin F2α-contracted arteries. In BAs 10−6 M PAF reduced the contraction by 17% and in PAs by 47%. The relaxant effects in both arteries were unaffected by indomethacin. In conclusion, PAF can act both as a constrictor and as a dilator of isolated feline and human cerebral arteries. The effects are seemingly unrelated to vascular prostanoid production.

scholarly journals EP1- and EP3-Receptors Mediate Prostaglandin E2–Induced Constriction of Porcine Large Cerebral Arteries

2004 ◽  
Vol 24 (12) ◽  
pp. 1305-1316 ◽  
Author(s):  
Vikram Jadhav ◽  
Anthony Jabre ◽  
Shinn-Zong Lin ◽  
Tony Jer-Fu Lee
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Receptor Antagonist ◽  
Cerebral Arteries ◽  
Muscle Cells ◽  
Prostaglandin E ◽  
Receptor Subtypes ◽  
Basilar Arteries ◽  
Cerebral Vascular

Prostaglandin E2 (PGE2) has been shown to dilate and constrict the systemic vascular beds, including cerebral vessels. The exact mechanism of PGE2-induced cerebral vasoconstriction, however, is less clarified. The authors' preliminary studies showed that PGE2 exclusively constricted the adult porcine basilar arteries. The present study, therefore, was designed to examine the receptor mechanisms involved in PGE2-induced constriction of large cerebral arteries in the adult pig. Results from an in vitro tissue-bath study indicated that PGE2 and its agonists 17-phenyl trinor PGE2 (17-PGE2), sulprostone (EP1/EP3 receptor agonists), and 11-deoxy-16,16-dimethyl PGE2 (11-PGE2, an EP2/EP3-receptor agonist) induced exclusive constriction, which was not affected by endothelium denudation or cold-storage denervation of perivascular nerves. The constriction induced by PGE2, 17-PGE2, and sulprostone, but not by potassium chloride, was blocked by SC-19220 (a selective EP1-receptor antagonist), AH-6809 (an EP1/EP2-receptor antagonist), and U-73122 and neomycin (phospholipase C inhibitors). AH-6809, however, did not affect 11-PGE2–induced contraction. These results suggest that the contraction was not mediated by the EP2-receptor, but was mediated by EP1- and EP3-receptors. Furthermore, EP1-receptor immunoreactivities were found across the entire medial smooth muscle layers, whereas EP3-receptor immunoreactivities were limited to the outer smooth muscle layer toward the adventitia. Western blotting also showed the presence of EP1- and EP3-receptor proteins in cultured primary cerebral vascular smooth muscle cells. In conclusion, PGE2 exclusively constricts the adult porcine large cerebral arteries. This constriction is mediated by phosphatidyl–inositol pathway via activation of EP1- and EP3-receptors located on the smooth muscle cells. These two receptor subtypes may play important roles in physiologic and pathophysiologic control of cerebral vascular tone.

scholarly journals Tachykinins (Substance P, Neurokinin A, Neuropeptide K, and Neurokinin B) in the Cerebral Circulation: Vasomotor Responses in vitro and in situ

1991 ◽  
Vol 11 (4) ◽  
pp. 567-575 ◽  
Author(s):  
I. Jansen ◽  
C. Alafaci ◽  
J. McCulloch ◽  
R. Uddman ◽  
L. Edvinsson
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Basilar Artery ◽  
Cerebral Arteries ◽  
Receptor Subtype ◽  
Neurokinin A ◽  
Neurokinin B ◽  
Neuropeptide K

The vasomotor responses of tachykinins have been studied in the cerebral vasculature of human, pig, cat, and guinea pig. Substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and neuropeptide K (NPK) induced concentration-dependent relaxations of precontracted cerebral arteries in all species when examined by a sensitive in vitro technique. In addition, the relaxant responses to SP, NKA, and NKB were studied in cat pial arterioles by peptide microapplication in situ. In human pial vessels, the order of relaxant potency was SP > NKB > NKA > NPK; in the pig middle cerebral artery, there was no difference in potency between the tachykinins; in the cat middle cerebral artery, SP = NKB > NKA = NPK; and in the guinea pig basilar artery, SP » NPK = NKA > NKB. Responses induced by SP, NKA, and NKB in the cat were comparable in vitro and in situ. Removal of the endothelium abolished relaxation induced by all four tachykinins. The relaxant responses of guinea pig basilar arteries to SP, NKA, and NPK were competitively antagonized by the SP antagonist Spantide. However, Spantide lowered the Imax of the NKB concentration–response curve without any rightward shift, suggesting action at a different site than the other tachykinins. In the guinea pig basilar artery, the relaxation seems to be exerted via a NK-1 receptor subtype while the receptor subtype is more unclear in cerebral arteries from human, cat, and pig. It is concluded that relaxations induced by SP, NKA, NKB, and NPK are dependent on the endothelium, and are antagonized either competitively or non-competitively by the SP antagonist Spantide. The origin of tachykinins acting through the endothelium is discussed.

scholarly journals Endotoxin Decreases the Contractile Responses of the Porcine Basilar Artery to Vasoactive Substances

1993 ◽  
Vol 13 (4) ◽  
pp. 712-719 ◽  
Author(s):  
Masami Ueno ◽  
Tony J.-F. Lee
Keyword(s):  
Endothelial Cells ◽  
Basilar Artery ◽  
Muscle Tone ◽  
Cerebral Arteries ◽  
Contractile Responses ◽  
Vasoactive Substances ◽  
Basilar Arteries ◽  
Arterial Reactivity ◽  
Lps Treatment

The effects of endotoxin (lipopolysaccharide; LPS) on the reactivity of isolated porcine basilar artery were examined using in vitro tissue bath techniques. The active muscle tone of the basilar arterial rings with or without endothelial cells induced by U46619 (1 μ M) reached a plateau in 15 min, which was stable for the first hour and gradually decreased during the next 5 h. This time-dependent decrease in tone was significantly potentiated in the presence of LPS (20 μg/ml). The potentiation by LPS was blocked by Nw-nitro-l-arginine (l-NNA; 60 μ M), methylene blue (10 μ M), and dexamethasone (1 μ M) but not by hemoglobin (1 μ M). The effect of l-NNA was readily reversed by l-arginine but not by d-arginine. Furthermore, the contractile responses of porcine basilar arterial rings with or without intact endothelium to U46619 and KCl were decreased following incubation with LPS (20 μg/ml) for 4 h. Similar hyporeactivity was observed in cold storage–denervated cerebral arteries incubated with LPS for 4 h. This decrease in contractile responses in LPS-treated rings was reversed by 60 μ M l-NNA and 1 μ M dexamethasone. These results indicate that LPS treatment renders the porcine basilar arteries hyporesponsive to vasoconstrictors. Since effects of LPS were not modified by the presence of endothelial cells and perivascular neurons, the alteration in cerebral arterial reactivity may be due in part to an enhanced formation of nitric oxide from l-arginine in the vascular smooth muscle cells.

Cerebral vasospasm: contractile activity of hemoglobin in isolated canine basilar arteries

1980 ◽  
Vol 53 (6) ◽  
pp. 787-793 ◽  
Author(s):  
Takeo Tanishima
Keyword(s):  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Contractile Activity ◽  
Cerebral Arteries ◽  
Adenosine Monophosphate ◽  
Active Species ◽  
Exchange Chromatography ◽  
Basilar Arteries ◽  
Chronic Cerebral Vasospasm

✓ Recent studies suggest the possible role of the red blood cell (RBC) in causing chronic cerebral vasospasm. However, the basic action of hemoglobin (Hb), the major component of the RBC, on cerebral arteries remains unknown. The present study was undertaken to analyze the contractile effects of human Hb (purified by ion-exchange chromatography) on canine arteries in vitro. The contractile activity of lysed RBC was shown to be derived from Hb. Hemoglobin in oxygenated form (oxyHb) caused a maximum contraction equal to about 70% of that induced by serotonin in the basilar artery. Ferrous Hb's (oxyHb and carboxyHb) produced much greater contraction than ferric Hb's (methemoglobin and cyanmethemoglobin), suggesting that superoxide radicals, an active species of oxygen, may be related to the contractile activity of Hb. Neither methysergide, phentolamine, mepyramine, nor aspirin inhibited the vasoconstrictive activity of oxyHb. This finding indicates that the activation of serotonergic, alpha-adrenergic, or histaminergic H1 receptors, or prostaglandin synthesis may not be involved in the mechanism of action of oxyHb. The constituents of Hb caused little or no contraction as compared with Hb as a whole. The basilar artery was more highly sensitive to Hb than arteries from other anatomical locations. Cyclic adenosine monophosphate caused a very slight decrease in the Hb-induced contraction. It is concluded that oxyHb can contract cerebral arteries in vitro. These results, coupled with recent reports on the participation of the RBC in producing chronic vasospasm, strongly suggest that oxyHb released from RBC's plays an important role in the pathogenesis of chronic cerebral vasospasm.

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