Effects of LY83583, nordihydroguaiaretic acid, and quinacrine on cyclic GMP elevation and inhibition of tension by muscarinic agonists in rabbit aorta and left atrium

Diamond, Jack

doi:10.1139/y87-297

Cited by 27 publications

(10 citation statements)

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“…The endothelium attenuates the spontaneous development of myogenic tone in the pig coronary artery, a phenomenon which is due to basal release of EDRF (22). Inhibition of the basal release of EDRF either by endothelium removal or by inhibitors of EDRF, methylene blue, LY83583, or hemoglobin (27)(28)(29) causes contractions and increases sensitivity of the pig coronary artery to contractile agents (7,22 Preliminary studies showed that ox-LDL causes significant, but smaller, contractions of pig coronary arteries with endothelium which are not contracted with U46619 (1.1±0.2 g, n = 6). Thus, the magnitude of contractions to ox-LDL depends upon preexisting tone which in this study was provided by the thromboxane A2-mimetic.…”

Section: Discussionmentioning

confidence: 99%

Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery.

Simon¹,

Cunningham²,

Cohen³

1990

J. Clin. Invest.

305

133

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The direct vasoactive effects of native and oxidatively modified low density lipoproteins as well as their effects on endothelium-dependent relaxations to 5-hydroxytryptamine were studied in isolated rings of pig right coronary artery. Slowly developing contractions were caused by native low density lipoproteins (100 gg protein/ml). The contractions were more pronounced in the absence than in the presence of the trace metal chelator, EDTA, and coincided with the formation of lipid peroxides during the response. The lipophilic antioxidant, butylated hydroxytoluene, prevented the oxidation of, and contraction to, native low density lipoproteins. Low density lipoproteins oxidized by exposure to copper contracted coronary arteries more rapidly with a threshold of only 1 gg protein/ml, but with a similar maximal contraction at 100 fg protein/ml. Superoxide dismutase inhibited the contraction to native low density lipoproteins, but not to oxidized low density lipoproteins. Catalase blocked contractions to both native and oxidized low density lipoproteins. Contractions to oxidized low density lipoproteins were unaffected by indomethacin, but were abolished by removal of the endothelium or by inhibitors of endothelium-derived relaxing factor. Oxidized low density lipoproteins but not native low density lipoproteins inhibited endothelium-dependent relaxations to 5-hydroxytryptamine.

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Section: Discussionmentioning

confidence: 99%

Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery.

Simon¹,

Cunningham²,

Cohen³

1990

J. Clin. Invest.

305

133

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“…The 5-lipoxygenase blocker, REV-5901, failed to influence the effects of the contractile agents, des-Arg9-BK or KCI. The inhibitor of the soluble form of guanylyl cyclase, LY-83583, also failed to inhibit the contractile effect of any of the two stimuli at a concentration that reportedly inhibits guanosine 3':5'-cyclic monophosphate (cyclic GMP) accumulation in the acetylcholine-stimulated rabbit aorta (Diamond, 1987). The major eicosanoid produced by the isolated aorta, either in the basal or stimulated conditions is PGI2 (Forstermann et al, 1984).…”

Section: Contractility Assaysmentioning

confidence: 98%

Vascular mode of action of kinin B₁ receptors and development of a cellular model for the investigation of these receptors

Lévesque

Drapeau

Grose

et al. 1993

British J Pharmacology

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1 Kinins exert a contractile effect on rabbit aortic rings via the stimulation of B, receptors. Des-Arg9-bradykinin (BK) is more potent than BK on this receptor type. The mode of action of des-Arg9-BK on rabbit aortic tissue has been studied by both the aortic ring contractility assay and a cellular model using cultured aortic smooth muscle cells (SMCs). 2 The des-Arg9-BK-induced contractions in rabbit aortic rings were unaffected by pretreatments with nifedipine, indomethacin, REV-5901 (a 5-lipoxygenase blocker) and LY-83583 (a guanylyl cyclase inhibitor); however, the protein kinase inhibitors H-7 and H-9 significantly reduced the maximal effect of des-Arg9-BK. 3 The contractile responses to des-Arg9-BK in calcium-free Krebs solution were slightly but not significantly attenuated in amplitude, as compared to paired control tissues bathed in Krebs solution, and sustained plateaus of contraction were observed in the absence of Ca2 . However, Ca2+ replenishment further increased the kinin-induced contraction measured in Ca2'-free bathing fluid. 4 Despite the lack of evidence of a mediating role for prostaglandin in the mechanical response to des-Arg9-BK, the kinin stimulated the release of prostacyclin from rabbit aorta rings measured as immunoreactive 6-keto-prostaglandin Fl,a (6-keto-PGF1,,).5 Smooth muscle cells (SMCs) derived from the rabbit aorta exhibit functional responses to des-Arg9-BK in acute release of 6-keto-PGF1, and of inositol phosphate turnover which were inhibited by pretreatment with the B1 receptor antagonist, Lys[Leu8]des-Arg9-BK, but not by the B2 receptor antagonist, Preincubation of the cells with interleukin-1 (IL-1) 20 h before stimulation with the kinin had no effect on basal inositol phosphate turnover, but potentiated the acute effect of des-Arg9-BK.6 These results suggest that second mesengers derived from the action of phospholipase C are produced by SMCs when B1 receptors are activated in rabbit aortic tissue. Intracellular calcium stores are primarily mobilized by des-Arg9-BK, although receptor-controlled calcium influx has not been ruled out, and may contribute to initiate the contractile responses. The maintenance of the contractile state involves protein kinase C activity and is consistent with a current model of SMC function. The cell model retains some of the cardinal properties of B1 receptor-mediated vascular responses: endotheliumindependent PGI2 release and up-regulation by the cytokine IL-1. PGI2 is not involved in the mechanical response, possible because the rabbit aorta is refractory to this prostaglandin.

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“…This compound blocks both basal and muscarinic receptor-mediated cGMP production in cardiac muscle (Schmidt, Sawyer, Truex, Marshall & Fleisch, 1985;Diamond, 1987), and dialysing cardiac myocytes with 10-30 uM LY-83583 has also been reported to block cGMP-mediated responses (Mubagwa, Shirayama, Moreau & Pappano, 1993;Han et al 1995 In the third set of experiments, we examined the effect of ODQ. This compound inhibits NO-stimulated guanylate cyclase activity with an EC50 of 0X01-0X1 /lM (Garthwaite, Southam, Boulton, Nielsen, Schmidt & Mayer, 1995;Brunner, Schmidt, Nielsen & Mayer, 1996).…”

Section: S I Zakharov Anomentioning

confidence: 99%

Rebound stimulation of the cAMP‐regulated Cl‐ current by acetylcholine in guinea‐pig ventricular myocytes.

Zakharov

Harvey

1997

The Journal of Physiology

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OH 44106-4970, USA 1. Acetylcholine (ACh)-induced rebound stimulation of the cAMP-regulated Cl-current was studied in isolated guinea-pig ventricular myocytes using dialysing and dialysis-limiting configurations of the whole-cell patch-clamp technique. 2. Exposure to and subsequent washout of ACh produced a transient rebound stimulation of the Cl-current. However, this rebound response was only observed in the presence of submaximally stimulating concentrations of the cAMP-producing agonists isoprenaline (Iso) or histamine. ACh-induced rebound stimulation was not observed in the presence of maximally stimulating concentrations of Iso, nor was it observed in the absence of Iso. 3. To prevent saturation of responses during rebound, the effects of ACh were studied in the presence of a subthreshold concentration of Iso (0-001 /M). Varying 4. Rebound stimulation of the Cl-current could also be elicited by washing in 2 /UM atropine during exposure to ACh, instead of washing out ACh. Furthermore, ACh-induced rebound was blocked by the M2 muscarinic receptor antagonist methoctramine but not by the Ml receptor antagonist pirenzepine. Rebound was also blocked in pertussis toxin (PTX)-treated myocytes.5. ACh-induced rebound stimulation was not blocked by: (a) L-NMMA, an inhibitor of nitric oxide synthase activity; (b) Methylene Blue, LY-83583, and ODQ, inhibitors of cGMP production; or (c) milrinone, an inhibitor of cGMP-dependent phosphodiesterase activity. 6. These results indicate that ACh can stimulate cAMP-regulated ion channel activity in cardiac ventricular myocytes by facilitating fl-adrenergic and histaminergic responses. This is opposite to the inhibitory actions more typically associated with muscarinic receptor stimulation in ventricular myocardium. This stimulatory effect of ACh is mediated through M2 muscarinic receptors and a PTX-sensitive G-protein, but it does not appear to involve the production of nitric oxide or cGMP.Parasympathetic stimulation exerts negative inotropic as channels, generally associated with atrial and pacemaker well as negative chronotropic effects on the heart. These cells of the heart. The indirect effects are due to antagonism inhibitory effects are mediated through the actions of the of sympathetic responses mediated by,f-adrenergic receptor neurotransmitter acetylcholine (ACh) at muscarinic stimulation of ion channels through a cAMP-protein cholinergic receptors (Loffelholz & Pappano, 1985). These kinase A (PKA)-dependent mechanism in all areas of the responses to muscarinic receptor stimulation involve both heart (Hartzell, 1988 (Hollenberg, Carriere & Barger, 1965;Levy, 1971;Burke & Calaresu, 1972;Loeb & Vassalle, 1979;Gilmour & Zipes, 1985 L-Type Ca!+ current was blocked by adding 1 /UM nisoldipine or 100 JSM Cd2+ to extracellular solutions. Na+ current and T-type Ca!+ current were inactivated by using a holding potential of -30 mV. Electrodes with resistances between 0 5 and 1P5 MQ2 were used for all experiments. When the perforated-patch technique was used, electrical acces...

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Effects of LY83583, nordihydroguaiaretic acid, and quinacrine on cyclic GMP elevation and inhibition of tension by muscarinic agonists in rabbit aorta and left atrium

Cited by 27 publications

References 0 publications

Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery.

Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery.

Vascular mode of action of kinin B₁ receptors and development of a cellular model for the investigation of these receptors

Rebound stimulation of the cAMP‐regulated Cl‐ current by acetylcholine in guinea‐pig ventricular myocytes.

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Effects of LY83583, nordihydroguaiaretic acid, and quinacrine on cyclic GMP elevation and inhibition of tension by muscarinic agonists in rabbit aorta and left atrium

Cited by 27 publications

References 0 publications

Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery.

Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery.

Vascular mode of action of kinin B1 receptors and development of a cellular model for the investigation of these receptors

Rebound stimulation of the cAMP‐regulated Cl‐ current by acetylcholine in guinea‐pig ventricular myocytes.

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Vascular mode of action of kinin B₁ receptors and development of a cellular model for the investigation of these receptors