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.

Calcium sensitivity of vasospastic basilar artery after experimental subarachnoid hemorrhage

2006 ◽  
Vol 290 (6) ◽  
pp. H2329-H2336 ◽  
Author(s):  
R. Loch Macdonald ◽  
Zhen-Du Zhang ◽  
Masataka Takahashi ◽  
Elena Nikitina ◽  
J. Young ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Smooth Muscle Cells ◽  
Arterial Wall ◽  
Arterial Compliance ◽  
Smooth Muscle Actin ◽  
Muscle Cells ◽  
Calcium Sensitivity ◽  
Basilar Arteries

Arteries that develop vasospasm after subarachnoid hemorrhage (SAH) may have altered contractility and compliance. Whether these changes are due to alterations in the smooth muscle cells or the arterial wall extracellular matrix is unknown. This study elucidated the location of such changes and determined the calcium sensitivity of vasospastic arteries. Dogs were placed under general anesthesia and underwent creation of SAH using the double-hemorrhage model. Vasospasm was assessed by angiography performed before and 4, 7, or 21 days after SAH. Basilar arteries were excised from SAH or control dogs ( n = 8–52 arterial rings from 2–9 dogs per measurement) and studied under isometric tension in vitro before and after permeabilization of smooth muscle with α-toxin. Endothelium was removed from all arteries. Vasospastic arteries demonstrated significantly reduced contractility to KCl with a shift in the EC50 toward reduced sensitivity to KCl 4 and 7 days after SAH ( P < 0.05, ANOVA). There was reduced compliance that persisted after permeabilization ( P < 0.05, ANOVA). Calcium sensitivity was decreased during vasospasm 4 and 7 days after SAH, as assessed in permeabilized arteries and in those contracted with BAY K 8644 in the presence of different concentrations of extracellular calcium ( P < 0.05, ANOVA). Depolymerization of actin with cytochalasin D abolished contractions to KCl but failed to alter arterial compliance. In conclusion, it is shown for the first time that calcium sensitivity is decreased during vasospasm after SAH in dogs, suggesting that other mechanisms are involved in maintaining the contraction. Reduced compliance seems to be due to an alteration in the arterial wall extracellullar matrix rather than the smooth muscle cells themselves because it cannot be alleviated by depolymerization of smooth muscle actin.

scholarly journals Norepinephrine and Acetylcholine Transmitter Mechanisms in Large Cerebral Arteries of the Pig

1982 ◽  
Vol 2 (4) ◽  
pp. 439-450 ◽  
Author(s):  
Tony Jer-Fu Lee ◽  
L. R. Kinkead ◽  
S. Sarwinski
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cerebral Artery ◽  
Direct Action ◽  
Cerebral Arteries ◽  
Muscle Cells ◽  
Direct Stimulation ◽  
Low Concentration

This study examines, using an in vitro tissue bath technique, the nature of the transmitter mechanism(s) in the pig cerebral artery. Of the arteries with intact endothelium, about 25% relaxed on application of acetylcholine (ACh) at low concentration (3 × 10−7 to 3 × 10−6 M) and constricted at concentrations exceeding 10−5 M. The remaining arterial preparations either constricted (61%) or exhibited no response (14%) at any concentration of ACh tested (3 × 10−7 to 3 × 10−3 M). On the other hand, none of the arteries without endothelium relaxed at any concentration of ACh tested (3 × 10−7 to 3 × 10−3 M); of these, 90% constricted and 10% exhibited no response. These results show that ACh-induced cerebral vasodilation is dependent on endothelial cells and the direct action of ACh on the vascular smooth muscle cells is constriction. Contrary to findings in the large cerebral arteries of the cat and several other species, about 90% of the pig cerebral arteries, with or without endothelium, dilated upon application of norepinephrine (NE) at low concentration (10−7 to 3 × 10−5 M) and constricted at concentrations exceeding 3 × 10−5 M. The NE dose–response relationships were not different in arteries with and without endothelial cells, indicating that the NE-induced vasodilation was independent of the endothelial cells. The relaxation and constriction were blocked by the respective β- and α-receptor antagonists, suggesting that both responses resulted from direct stimulation by NE of β and α receptors on the smooth muscle cells. Transmural nerve stimulation (TNS) consistently induced vasodilation of the arteries whether or not the endothelial cells were present. The vasodilation was abolished by tetrodotoxin (TTX) and cold storage denervation. The TNS-induced vasodilation was not smaller in arteries without endothelium than in those with endothelium. This suggests that TNS-induced vasodilation was independent of the endothelial cells. When examined histochemically, the pig cerebral artery exhibited rich catecholamine fluorescence. Biochemical assays indicate that NE is the primary catecholamine. However, the TNS-induced vasodilation was not affected by atropine, guanethidine, or propranolol, nor prevented by reserpine. It is suggested that an as yet unidentified transmitter is responsible for the TNS-induced vasodilation. Results of this study suggest that the nerve-released ACh is a potential vasoconstrictor transmitter and that NE is a potential vasodilator transmitter in the large cerebral artery of the pig. The neurogenic control of the pig cerebral circulation may be different from that of other species, including humans.

Effect of hypoxia on the contractile response to KCl, prostaglandin F2α, and hemoglobin

1987 ◽  
Vol 67 (4) ◽  
pp. 565-572 ◽  
Author(s):  
Tadayoshi Nakagomi ◽  
Neal F. Kassell ◽  
Tomio Sasaki ◽  
Shigeru Fujiwara ◽  
R. Michael Lehman ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Contractile Response ◽  
Direct Action ◽  
Cerebral Arteries ◽  
Prostaglandin F2α ◽  
Muscle Cells ◽  
Content Type ◽  
Fine Print

✓ The purpose of this experiment was to evaluate the effect of hypoxia on the in vitro contractile responses of canine basilar artery to KCl, prostaglandin (PG) F2α, and hemoglobin. Hypoxia was induced by changing the bubbling gas mixture in the chamber from 95% O2/5% CO2 to 95% N2/5% CO2. Hypoxia augmented the contractile response developed at 95% O2 to 25 mM and 50 mM KCl, 3 × 10−7 M and 10−5 M PGF2α, and 10−6 M hemoglobin. No significant alteration of the hypoxic augmentation in any preparation exposed to 25 mM KCl, 3 × 10−7 M PGF2α, or 10−6 M hemoglobin was observed with guanethidine (10−5 M), prazosin (10−5 M), methysergide (10−5 M), or diphenhydramine (10−5 M). Endothelial denudation did not affect hypoxic augmentation. Hypoxia did not cause any alteration of the contractile response to 10−6 M PGF2α in Ca++-free media. Pretreatment with a calcium channel blocker, nicardipine, significantly inhibited the hypoxic potentiation of the contractile response to 25 mM KCl, 3 × 10−7 M PGF2α, and 10−6 M hemoglobin. These results suggest that hypoxia augments the contractile response to these agonists by a direct action on the smooth-muscle cells, facilitating the transmembrane influx of extracellular calcium. Hypoxia of smooth-muscle cells in the major cerebral arteries might be involved in the pathogenesis of vasospasm.

Effect of SR 47436, a novel angiotensin II AT1 receptor antagonist, on human vascular smooth muscle cells in vitro

1994 ◽  
Vol 251 (2-3) ◽  
pp. 143-150 ◽  
Author(s):  
Jean-Marc Herbert ◽  
Chantal Delisée ◽  
Frédérique Dol ◽  
Paul Schaeffer ◽  
Catherine Cazaubon ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Receptor Antagonist ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
At1 Receptor

Epicardial Cells of Human Adults Can Undergo an Epithelial-to-Mesenchymal Transition and Obtain Characteristics of Smooth Muscle Cells In Vitro

Stem Cells ◽  
2007 ◽  
Vol 25 (2) ◽  
pp. 271-278 ◽  
Author(s):  
John van Tuyn ◽  
Douwe E. Atsma ◽  
Elizabeth M. Winter ◽  
Ietje van der Velde-van Dijke ◽  
Daniel A. Pijnappels ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Muscle Cells ◽  
Mesenchymal Transition ◽  
Epicardial Cells ◽  
Human Adults

Characterization of opioid receptors on smooth muscle cells from guinea pig stomach

1992 ◽  
Vol 262 (3) ◽  
pp. G461-G469 ◽  
Author(s):  
L. Zhang ◽  
Z. F. Gu ◽  
T. Pradhan ◽  
R. T. Jensen ◽  
P. N. Maton
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Opioid Receptors ◽  
Muscle Cells ◽  
Receptor Subtypes ◽  
Selective Antagonist ◽  
Kappa Agonist ◽  
Gastric Smooth Muscle ◽  
Selective Ligand ◽  
Guinea Pig Stomach

On the basis of opioid-stimulated contraction of dispersed gastric smooth muscle cells it has been suggested that these cells possess opioid receptors of three subtypes: kappa (kappa), mu (mu), and delta (delta). We have used selective peptidase-resistant radioligands, agonists and antagonists, to examine receptor subtypes on dispersed gastric smooth muscle cells from guinea pigs prepared by collagenase digestion. The kappa-agonist U-50488H, the mu-agonist [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAGO), and the delta-agonist [D-Pen2,Pen5]enkephalin (DPDPE) each caused muscle contraction. The concentrations required to caused half-maximal contraction were U50488H (6 pM) greater than DAGO (13 pM) greater than DPDPE (6 nM). The abilities of these agonists to inhibit binding of [3H]U-69593 (kappa-preferring) by 50% were U50488H (43 nM) greater than DAGO (43 microM) greater than DPDPE (200 microM). Their abilities to inhibit binding of [3H]naloxone (mu-preferring) by 50% were DAGO (0.2 microM) greater than U50488H (10 microM) greater than DPDPE (greater than 100 microM). No binding could be detected with the delta-selective ligand [3H]DPDPE. The kappa-preferring antagonist Mr2266 (10 nM) preferentially inhibited contraction stimulated by the kappa-agonist U50488H, and naltrexone (10 nM) (mu-selective antagonist) preferentially inhibited contraction stimulated by the mu-agonist DAGO. ICI 174864 (200 microM; delta-selective antagonist) had no effect on contraction stimulated by mu-, kappa-, or delta-agonists. Contraction stimulated by the delta-agonist DPDPE was inhibited by both kappa- and mu-receptor antagonists. Studies on the effect of the antagonists on binding of [3H]naloxone and [3H]U69593 also provided evidence for kappa- and mu-sites but nor for delta-sites.(ABSTRACT TRUNCATED AT 250 WORDS)

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