NO-mediated MaxiKCa channel activation produces relaxation of guinea pig aorta independently of voltage-dependent L-type Ca2+ channels

Tanaka, Yoshio; Igarashi, Tomomi; Kaneko, Hiroki; Yamaki, Fumiko; Mochizuki, Yumi; Aida, Miwako; Taniguchi, Haruyori; Tanaka, Hikaru; Shigenobu, Koki

doi:10.1016/s0306-3623(00)00056-2

Cited by 14 publications

(9 citation statements)

References 28 publications

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“…Endothelium‐denuded rings failed to respond to ACh. It should be noted that ACh‐induced relaxations are attenuated in preparations precontracted with high KCl rather than noradrenaline, because NO‐mediated membrane hyperpolarization in these preparations is too weak to counteract the effect of the depolarization induced by the high KCl 10 . In preliminary experiments, we found that, in terms of magnitude, a > 25% relaxation induced by 10 −5 mol/L ACh in rings precontracted with 60 mmol/L KCl was similar to a > 80% relaxation response to 10 −5 mol/L ACh in rings precontracted with 10 −7 mol/L phenylephrine.…”

Section: Methodsmentioning

confidence: 99%

Direct Effect of Dexmedetomidine on Rat Isolated Aorta Involves Endothelial Nitric Oxide Synthesis and Activation of the Lipoxygenase Pathway

Kim

Sohn

Jeong

et al. 2009

Clin Exp Pharma Physio

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1. The aims of the present in vitro study were to examine the roles of pathways associated with arachidonic acid metabolism in dexmedetomidine-induced contraction and to determine which endothelium-derived vasodilators are involved in the endothelium-dependent attenuation of vasoconstriction elicited by dexmedetomidine. 2. Dexmedetomidine (10(-9)-10(-6) mol/L) concentration-response curves were constructed in: (i) aortic rings with no drug pretreatment; (ii) endothelium-denuded aortic rings pretreated with either 2 x 10(-5) mol/L quinacrine dihydrochloride, 10(-5) mol/L nordihydroguaiaretic acid (NDGA), 3 x 10(-5) mol/L indomethacin or 10(-5) mol/L fluconazole; and (iii) endothelium-intact aortic rings pretreated with either 5 x 10(-5) mol/L N(G)-nitro-l-arginine methyl ester (l-NAME), 10(-5) mol/L fluconazole, 10(-5) mol/L indomethacin, 10(-5) mol/L glibenclamide, 5 x 10(-3) mol/L tetraethylammonium or 5 x 10(-5) mol/L l-NAME plus rauwolscine (10(-5), 10(-6) mol/L). The production of nitric oxide (NO) metabolites was determined in human umbilical vein endothelial cells treated with dexmedetomidine. 3. Quinacrine dihydrochloride, NDGA and indomethacin attenuated the dexmedetomidine-induced contraction of endothelium-denuded rings. Dexmedetomidine (10(-7)-10(-6) mol/L)-induced contractions of endothelium-denuded rings were enhanced compared with those of endothelium-intact rings, as were dexmedetomidine-induced contractions of endothelium-intact rings pretreated with l-NAME or tetraethylammonium. Rauwolscine attenuated dexmedetomidine-induced contractions in endothelium-intact rings pretreated with l-NAME. Dexmedetomidine (10(-6) mol/L) was found to activate NO production. 4. Taken together, the results indicate that dexmedetomidine-induced contraction of aortic rings involves activation of the lipoxygenase and cyclo-oxygenase pathways and is attenuated by increased NO production following stimulation of endothelial alpha(2)-adrenoceptors by dexmedetomidine.

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Section: Methodsmentioning

confidence: 99%

Direct Effect of Dexmedetomidine on Rat Isolated Aorta Involves Endothelial Nitric Oxide Synthesis and Activation of the Lipoxygenase Pathway

Kim

Sohn

Jeong

et al. 2009

Clin Exp Pharma Physio

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“…2ϩ -ACTIVATED K ϩ CHANNELS (BK) are present in a variety of cell types and have been studied in the uterus (35), brain (22,24,25), and smooth muscle cells of various vascular beds (8,19,21,26,32,34). Our laboratory has previously described BK in human mesangial cells (29), smooth muscle-like cells of the renal glomeruli that participate in regulating the rate of filtration (3,14,15).…”

Section: Large Camentioning

confidence: 99%

Role of hβ₁in activation of human mesangial BK channels by cGMP kinase

Kudlacek

Pluznick

et al. 2003

American Journal of Physiology-Renal Physiology

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In vascular smooth muscle and glomerular mesangial cells, relaxing agents such as nitric oxide and atrial natriuretic peptide activate large-conductance Ca2+-activated K+ channels (BK) via the cGMP kinase pathway. BK are composed of pore-forming alpha-subunits, encoded by the slopoke gene (Slo), and one of four cell-specific accessory beta-subunits (hbeta1-4). We used patch-clamp analysis to determine the influence of hbeta1, hbeta2, and hbeta4 on activation of human mesangial BK by cGMP kinase. We found that HEK 293 cells, coexpressing human (h) Sloalpha with either hbeta1 or hbeta2, contained single BK currents activated by db-cGMP in cell-attached patches. However, recombinant BK were not activated by db-cGMP when hSloalpha was expressed alone or with hbeta4. DNA-RNA hybridization revealed that mesangial cells contained mRNA for hbeta1 but not hbeta2 or hbeta4. The BK response to db-cGMP was decreased when hbeta1 antisense but not scrambled oligonucleotides were incorporated into mesangial cells. Western blot analysis showed that hbeta1 antisense oligonucleotide inhibited the amount of hbeta1-V5 fusion protein expressed in HEK 293 cells by approximately 50%. These results show that mesangial cells contain hbeta1, a BK accessory protein, which confers activation of BK by cGMP kinase.

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“…cGMP is a second messenger that activates protein kinases such as PKGI, highly expressed in smooth muscle cells and involved in vasorelaxation via ion channel control [55][56][57][58]. Moreover cGMP plays an important role in inhibition of platelet aggregation [59].…”

Section: Phosphodiesterase (Pde) Inhibitors and Ischemic Penumbramentioning

confidence: 99%

Saving the Ischemic Penumbra: Potential Role for Statins and Phosphodiesterase Inhibitors

Sallustio

Diomedi

Centonze

et al. 2007

CVP

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Ischemic stroke is the third cause of death and the most common cause of neurological disability. A main target of treatment is the still salvageable tissue surrounding the core of infarction and called "ischemic penumbra". Up to now the only drug approved for the treatment of acute ischemic stroke is recombinant tissue plasminogen activator to achieve early arterial recanalization and hypoxic tissue reperfusion and improve neural function. However, thrombolytic therapy has to be administered soon after the event since its efficacy is time dependent. This intervention also carries an increased risk of hemorrhagic transformation. In the rescue of poorly perfused cerebral regions an important role is played by collateral blood supply through the circle of Willis and through small pial vessels surrounding the lesion. The extent of collateralization is variable and at least in part regulated by the modulation of arteriolar nitric oxide (NO)-dependent endothelial function. Drugs that can improve endothelial function and cerebrovascular reactivity could have a role in collateral formation and infarct volume limitation. Statins affect endothelial NO production demonstrating their potential to influence endothelial NO synthase (eNOS) and in treating stroke. Phosphodiesterase (PDE) inhibitors improve functional recovery after stroke in rats enhancing neuro and synapto genesis and increasing guanosine 3,5-cyclic monophosphate (cGMP). The aim of this review is to highlight the potential of these two classes of drugs in the treatment of acute ischemic stroke by analysing their pharmacological effects and involvement in the NO and cGMP pathways.

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NO-mediated MaxiKCa channel activation produces relaxation of guinea pig aorta independently of voltage-dependent L-type Ca2+ channels

Cited by 14 publications

References 28 publications

Direct Effect of Dexmedetomidine on Rat Isolated Aorta Involves Endothelial Nitric Oxide Synthesis and Activation of the Lipoxygenase Pathway

Direct Effect of Dexmedetomidine on Rat Isolated Aorta Involves Endothelial Nitric Oxide Synthesis and Activation of the Lipoxygenase Pathway

Role of hβ₁in activation of human mesangial BK channels by cGMP kinase

Saving the Ischemic Penumbra: Potential Role for Statins and Phosphodiesterase Inhibitors

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NO-mediated MaxiKCa channel activation produces relaxation of guinea pig aorta independently of voltage-dependent L-type Ca2+ channels

Cited by 14 publications

References 28 publications

Direct Effect of Dexmedetomidine on Rat Isolated Aorta Involves Endothelial Nitric Oxide Synthesis and Activation of the Lipoxygenase Pathway

Direct Effect of Dexmedetomidine on Rat Isolated Aorta Involves Endothelial Nitric Oxide Synthesis and Activation of the Lipoxygenase Pathway

Role of hβ1in activation of human mesangial BK channels by cGMP kinase

Saving the Ischemic Penumbra: Potential Role for Statins and Phosphodiesterase Inhibitors

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Role of hβ₁in activation of human mesangial BK channels by cGMP kinase