Vascular effects of some opioid receptor agonists

1991 ◽  
Vol 69 (6) ◽  
pp. 846-851 ◽  
Author(s):  
T. Y. El-Sharkawy ◽  
M. F. Al-Shireida ◽  
C. W. T. Pilcher
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Endogenous Opioids ◽  
Vascular Effects ◽  
High Potassium ◽  
Opioid Agonists ◽  
Low Concentrations ◽  
Prostaglandin F ◽  
High Concentrations ◽  
High Doses

Opioid peptides have been implicated in shock-associated hypotension. Our aim was to find out whether opioid agonists have direct vasodilator actions on vascular smooth muscle. The study was conducted on rat abdominal aortic rings. In rings precontracted with either norepinephrine, prostaglandin F2α, or high potassium Krebs (HPK), the effects of the opioid agonists tested (morphine, U50488H, ethylketocyclazocine (EKC), and bremazocine) depended on the precontracting agent used. HPK-precontracted rings were relaxed by all agonists tested. In norepinephrine-precontracted rings, all caused contraction at low concentrations and relaxation at high concentrations except bremazocine, which caused only relaxation. In prostaglandin F2α-precontracted rings, U50488H produced contraction at low concentrations and relaxation at high concentrations while EKC caused only relaxation and morphine or bremazocine caused only contraction. All relaxant responses were endothelium-independent and were antagonized by verapamil but not by a number of antagonists including naloxone, MR2266, propranolol, diphenhydramine, cimetidine, and indomethacin. They may reflect calcium channel blockade. Morphine-induced vasoconstriction was antagonized by high concentrations of naloxone or mepyramine and may be due to release of histamine by a naloxone-sensitive mechanism. We conclude that (a) the opioid agonists tested exert direct actions on vascular smooth muscle; (b) the nature of the response depended not only on the agonist used and its concentration but also on the agent used to precontract the tissue; and (c) it is unlikely that direct actions of endogenous opioids contribute to the shock-associated hypotension because high doses were needed to elicit them.Key words: vascular smooth muscle, opioids, neurohormonal peptides, circulatory shock.

scholarly journals Are the Vascular Effects of Naloxone Attributable to the Preservatives Methyl- and Propylparaben?

1983 ◽  
Vol 3 (3) ◽  
pp. 395-398 ◽  
Author(s):  
Lennart Brandt ◽  
Karl-Erik Andersson ◽  
Bengt Hindfelt ◽  
Bengt Ljunggren ◽  
John D. Pickard
Keyword(s):  
Cerebrospinal Fluid ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Rapid Onset ◽  
Vascular Effects ◽  
Prostaglandin F

In vitro, the Nalonee® preparation of naloxone caused a concentration-dependent relaxation of human pial cortical arteries contracted by potassium, noradrenaline, serotonin, prostaglandin F2α (PGF2α), and haemorrhagic cerebrospinal fluid, or inhibited contractions elicited by these agents. However, the preservatives in the Nalonee preparation, methyl- and propylparaben, had similar effects. Pure naloxone alone had no effect on potassium or PGF2α-induced contractions. It is suggested that the relaxant effects on vascular smooth muscle of Nalonee can be attributed to the alkylparabens rather than to naloxone. The pronounced relaxations induced by the alkylparabens had a rapid onset, and they were stable and could easily be cleared after rinsing.

Effects of the β-Receptor Antagonists Propranolol, Oxprenolol and Labetalol on Human Vascular Smooth-Muscle Contraction

1978 ◽  
Vol 55 (3) ◽  
pp. 235-240
Author(s):  
R. F. W. Moulds ◽  
R. A. Jauernig ◽  
J. D. Hobson ◽  
J. Shaw
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Barium Chloride ◽  
Smooth Muscle Contraction ◽  
Hypotensive Activity ◽  
Inhibitory Effects ◽  
Vascular Effects ◽  
High Concentrations ◽  
Β Receptor

1. Spiral strips of human digital arteries have been studied in vitro to investigate whether dl-propranolol, d-propranolol, oxprenolol and labetalol have peripheral vascular effects in man. 2. Labetalol was a potent inhibitor of contractile responses to noradrenaline, but had less effect on responses to 5-hydroxytryptamine and barium chloride. 3. dl-and d-propranolol were equally effective inhibitors of responses to barium chloride. They were only weak antagonists of noradrenaline responses, but stronger, non-competitive antagonists of 5-hydroxytryptamine responses. 4. Oxprenolol was only a weak inhibitor of the responses to both noradrenaline and 5-hydroxytryptamine and had little effect on responses to barium chloride. 5. It is concluded that labetalol has specific α-adrenoreceptor-blocking properties, which are probably relevant to its therapeutic action in man. Propranolol has non-specific inhibitory effects on vascular smooth muscle, which might contribute to its hypotensive activity at high concentrations, but oxprenolol has only slight peripheral effects that are probably therapeutically insignificant.

Modulation of vascular tone by neutrophils: dependence on endothelial integrity

1989 ◽  
Vol 257 (4) ◽  
pp. H1315-H1320
Author(s):  
J. L. Mehta ◽  
D. L. Lawson ◽  
W. W. Nichols ◽  
P. Mehta
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Relaxant ◽  
Muscle Tone ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Smooth Muscle Tone ◽  
High Concentrations ◽  
Vascular Smooth Muscle Tone ◽  
Smooth Muscle Relaxant

To determine the influence of polymorphonuclear leukocytes (PMNLs) on vascular smooth muscle tone, isolated human PMNLs (10(4)–10(7) cells/ml) were suspended in a tissue bath with precontracted rat aortic rings with or without endothelium. PMNLs in low concentrations (10(4) and 10(5) cells/ml) caused a mild contraction, and in higher concentrations (10(6) and 10(7) cells/ml) caused a modest relaxation of aortic rings with intact endothelium. In contrast, PMNLs caused a potent concentration-dependent relaxation of deendothelialized rings (P less than 0.01 compared with rings with intact endothelium). The PMNL-induced vascular smooth muscle relaxation was abolished by both hemoglobin and methylene blue and potentiated by both superoxide dismutase and captopril. Although suspension of PMNLs caused release of eicosanoids, thromboxane A2 and prostacyclin, from rings with intact endothelium, neither indomethacin nor the TxA2-endoperoxide receptor antagonist SQ 29548 modified the effects of PMNLs on vascular smooth muscle tone. These observations suggest that unstimulated PMNLs generate a smooth muscle relaxant, which has biological characteristics similar to the endothelium-derived relaxing factor. Since the activity of this PMNL-derived smooth muscle relaxant is more pronounced in deendothelialized vascular segments, it appears that endothelium provides a barrier against vasorelaxation by high concentrations of PMNLs.

Furosemide-sensitive thallium fluxes in smooth muscle of rabbit uterus

1983 ◽  
Vol 245 (6) ◽  
pp. F778-F783
Author(s):  
A. Johns ◽  
S. V. Cutshaw
Keyword(s):  
Smooth Muscle ◽  
Binding Sites ◽  
Rank Order ◽  
Chloride Concentration ◽  
Cation Binding ◽  
Exchange System ◽  
Total Uptake ◽  
Low Concentrations ◽  
Chloride Pump ◽  
High Concentrations

The furosemide-sensitive uptake of thallium represents approximately equal to 50% of the total uptake of thallium by rabbit uterus and requires Cl- and Na+. The furosemide-sensitive uptake of thallium is stimulated by other ions at low concentrations with the rank order Li+ greater than Tl+ greater than K+ = Rb+ greater than Cs+ and is inhibited by these ions at high concentrations with the rank order Tl+ greater than K+ = Rb+ greater than Cs+ greater than Li+, suggesting multiple cation binding sites on the carrier. Uptake of 36Cl- is inhibited by furosemide in the presence of ouabain. Thallium efflux and 36Cl efflux in the presence of ouabain is inhibited by furosemide. The chloride concentration regulates the proportion of thallium uptake that is ouabain sensitive and furosemide sensitive without altering the total uptake. It is suggested that the furosemide-sensitive uptake of thallium reflects a Na+-Cl- -K+ exchange system that could be classified as a cotransport or countertransport of any two of these ions and also could be the smooth muscle chloride pump.

scholarly journals Biphasic Dose–Response Induced by PCB150 and PCB180 in HeLa Cells and Potential Molecular Mechanisms

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932582091004
Author(s):  
Ainy Zehra ◽  
Muhammad Zaffar Hashmi ◽  
Abdul Majid Khan ◽  
Tariq Malik ◽  
Zaigham Abbas
Keyword(s):  
Hela Cells ◽  
Molecular Mechanisms ◽  
Dependent Manner ◽  
Genotoxic Effects ◽  
Species Formation ◽  
Low Concentrations ◽  
Extracellular Signal ◽  
High Concentrations ◽  
High Doses ◽  
Dose Dependent

The polychlorinated biphenyls (PCBs) are persistent and their dose-dependent toxicities studies are not well-established. In this study, cytotoxic and genotoxic effects of PCB150 and PCB180 in HeLa cells were studied. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that the cell proliferation was stimulated at low doses (10−3 and 10−2 µg/mL for 12, 24, 48, and 72 hours) and inhibited at high doses (10 and 15 µg/mL for 24, 48, and 72 hours) for both PCBs. Increase in reactive oxygen species formation was observed in the HeLa cells in a time- and dose-dependent manner. Malondialdehyde and superoxide dismutase showed increased levels at high concentrations of PCBs over the time. Glutathione peroxidase expression was downregulated after PCBs exposure, suggested that both PCB congeners may attributable to cytotoxicity. Comet assay elicited a significant increase in genotoxicity at high concentrations of PCBs as compared to low concentrations indicating genotoxic effects. PCB150 and PCB180 showed decrease in the activity of extracellular signal–regulated kinase 1/2 and c-Jun N-terminal kinase at high concentrations after 12 and 48 hours. These findings may contribute to understanding the mechanism of PCBs-induced toxicity, thereby improving the risk assessment of toxic compounds in humans.

Hydrogen sulfide-induced relaxation of resistance mesenteric artery beds of rats

2004 ◽  
Vol 287 (5) ◽  
pp. H2316-H2323 ◽  
Author(s):  
Youqin Cheng ◽  
Joseph Fomusi Ndisang ◽  
Guanghua Tang ◽  
Kun Cao ◽  
Rui Wang
Keyword(s):  
Smooth Muscle ◽  
Hydrogen Sulfide ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Mesenteric Artery ◽  
Muscle Cells ◽  
Mesenteric Arteries ◽  
Vascular Effects ◽  
Rat Mesenteric Artery

Hydrogen sulfide (H2S) has been shown recently to function as an important gasotransmitter. The present study investigated the vascular effects of H2S, both exogenously applied and endogenously generated, on resistance mesenteric arteries of rats and the underlying mechanisms. Both H2S and NaHS evoked concentration-dependent relaxation of in vitro perfused rat mesenteric artery beds (MAB). The sensitivity of MAB to H2S (EC50, 25.2 ± 3.6 μM) was about fivefold higher than that of rat aortic tissues. Removal of endothelium or coapplication of charybdotoxin and apamin to endothelium-intact MAB significantly reduced the vasorelaxation effects of H2S. The H2S-induced relaxation of MAB was partially mediated by ATP-sensitive K+ (KATP) channel activity in vascular smooth muscle cells. Pinacidil (EC50, 1.7 ± 0.1 μM, n = 6) mimicked, but glibenclamide (10 μM, n = 6) suppressed, the vasorelaxant effect of H2S. KATP channel currents in isolated mesenteric artery smooth muscle cells were significantly augmented by H2S. l-Cysteine, a substrate of cystathionine-γ-lyase (CSE), at 1 mM increased endogenous H2S production by sixfold in rat mesenteric artery tissues and decreased contractility of MAB. dl-Propargylglycine (a blocker of CSE) at 10 μM abolished l-cysteine-dependent increase in H2S production and relaxation of MAB. Our results demonstrated a tissue-specific relaxant response of resistance arteries to H2S. The stimulation of KATP channels in vascular smooth muscle cells and charybdotoxin/apamin-sensitive K+ channels in vascular endothelium by H2S represents important cellular mechanisms for H2S effect on MAB. Our study also demonstrated that endogenous CSE can generate sufficient H2S from exogenous l-cysteine to cause vasodilation. Future studies are merited to investigate direct contribution of endogenous H2S to regulation of vascular tone.

Analysis of purine- and pyrimidine-induced vascular responses in the isolated rat cerebral arteriole

2001 ◽  
Vol 280 (2) ◽  
pp. H767-H776 ◽  
Author(s):  
Tetsuyoshi Horiuchi ◽  
Hans H. Dietrich ◽  
Shinichiro Tsugane ◽  
Ralph G. Dacey
Keyword(s):  
Smooth Muscle ◽  
Pyridoxal Phosphate ◽  
Disulfonic Acid ◽  
Dependent Manner ◽  
Cerebral Microvessels ◽  
Vascular Responses ◽  
Single Receptor ◽  
Low Concentrations ◽  
High Concentrations ◽  
Cerebral Arteriole

Effects of extraluminal UTP were studied and compared with vascular responses to ATP and its analogs in rat cerebral-penetrating arterioles. UTP, UDP, 2-methylthio-ATP, and α,β-methylene-ATP dilated arterioles at the lowest concentration and constricted them at high concentrations. Low concentrations of ATP dilated the vessels; high concentrations caused a biphasic response, with transient constriction followed by dilation. Endothelial impairment inhibited ATP- and UTP-mediated dilation and potentiated constriction to UTP but not to ATP. ATP- and 2-methylthio-ATP- but not UTP-mediated constrictions were inhibited by desensitization with 10−6M α,β-methylene-ATP or 3 × 10−6M pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS). PPADS at 10−4M abolished the UTP-mediated constriction and induced vasodilation in a dose-dependent manner but did not affect the dilation to ATP. These results suggest that in rat cerebral microvessels 1) ATP and 2-methylthio-ATP induce transient constriction via smooth muscle P2X1receptors in the cerebral arteriole, 2) UTP stimulates two different classes of P2Yreceptors, resulting in constriction (smooth muscle P2Y4) and dilation (possibly endothelial P2Y2), and 3) ATP and UTP produce dilation by stimulation of a single receptor (P2Y2).

Vascular α2-adrenoceptors can mediate nerve stimulation-evoked contractions

1985 ◽  
Vol 68 (s10) ◽  
pp. 117s-120s ◽  
Author(s):  
James R. Docherty ◽  
Lisa Hyland
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Nerve Stimulation ◽  
Saphenous Vein ◽  
Human Saphenous Vein ◽  
Α2 Adrenoceptors ◽  
Low Concentrations ◽  
Evoked Contractions ◽  
Α2 Receptors

1. It is now established that α2-adrenoceptors can be present on vascular smooth muscle as targets for exogenous agonists, but some controversy exists as to whether these vascular α2-receptors may also be the target for neurally released noradrenaline. 2. In human saphenous vein we have found evidence that the α2-antagonist yohimbine in low concentrations (0.01 μmol/l) can significantly inhibit stimulation-evoked contractions, whereas the α1-antagonist prazosin is more than ten times less potent. 3. It is concluded that, at least in some tissues, neuro-effector transmission can be mediated by vascular α2-adrenoceptors.

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