Age-Related Disappearance of the Inhibitory Effect of Vascular Endothelium on Agonist-Induced Vasoconstriction in Rat Mesenteric Vascular Beds

Jin, Xin; Satoh-Otonashi, Yukiko; Zamami, Yoshito; Hobara, Norio; Koyama, Toshihiro; Sun, Pengyuan; Li, Simin; Kitamura, Yoshihisa; Kawasaki, Hiromu

doi:10.1254/jphs.09183fp

Cited by 10 publications

(6 citation statements)

References 30 publications

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“…In the present study, the major findings are that exogenously applied acetylcholine and A23187 in the mouse perfused mesenteric vascular bed caused a concentrationdependent vasodilation, which is well consistent with the response in the rat perfused mesenteric vascular bed (13,14). Since responses to both acetylcholine and A23187 were abolished by endothelium dysfunction, they appear to be dependent on an intact endothelium, although the underlying signaling pathways differ between acetylcholine and A23187.…”

Section: Discussionsupporting

confidence: 85%

“…1, A and B, an initial phase of methoxamine-induced vasoconstriction was augmented by endothelium dysfunction. A previous report has demonstrated that in rat mesenteric arteries, endothelium acts to depress methoxamine-induced vasoconstriction by releasing EDHF (14,24). Therefore, EDRF and/or EDHF in the endothelium of mouse mesenteric arteries is likely to suppress methoxamine-induced vasoconstrictions.…”

Section: A23187 (Nmol)mentioning

confidence: 90%

“…In the rat mesenteric vascular bed, L-NAME at 100 μM has been shown to have weak inhibitory effects on acetylcholineand A23187-induced vasodilation (13,14). Furthermore, we have reported that L-NAME could inhibit NOS at concentrations lower than 100 μM in rat mesenteric arteries (25).…”

Section: A23187 (Nmol)mentioning

confidence: 90%

“…In rat mesenteric arteries, EDHF is responsible for acetylcholine-and A23187-induced vasodilation, since both responses were inhibited by K + channel inhibitors including tetraethylammonium, high K + medium, and apamin plus charybdotoxin, but not an ATP-sensitive K + channel inhibitor (13,14). Additionally, the involvement of gap-junctions in acetylcholine-mediated vasodilation in the rat mesenteric vascular bed has been demonstrated by inhibition of the response with 18α-glycyrrhetinic acid (gap-junction inhibitor) (13 (7,29).…”

Section: A23187 (Nmol)mentioning

confidence: 97%

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Endothelium-Derived Relaxing Factor–Mediated Vasodilation in Mouse Mesenteric Vascular Beds

et al. 2012

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Abstract. The endothelium in rat mesenteric vascular beds has been demonstrated to regulate vascular tone by releasing mainly endothelium-derived hyperpolarizing factor (EDHF), which is involved in the activation of K + channels and gap-junctions. However, it is unclear whether the endothelial system in mouse resistance arteries contributes to regulation of the vascular tone. The present study was designed to investigate the role of the endothelium using acetylcholine and A23187 (Ca 2+ ionophore) in mesenteric vascular beds isolated from male C57BL/6 mice and perfused with Krebs solution to measure perfusion pressure. In preparations with active tone produced by methoxamine in the presence of guanethidine, injections of acetylcholine, A23187, and sodium nitroprusside (SNP) caused a concentration-dependent decrease in perfusion pressure due to vasodilation. The vasodilator responses to acetylcholine and A23187, but not SNP, were abolished by endothelium dysfunction and significantly inhibited by N ω -nitro-L-arginine methyl ester (nitric oxide synthase inhibitor) and tetraethylammonium (K + -channel inhibitor) but not glibenclamide (ATP-sensitive K + -channel inhibitor). Indomethacin (cyclooxygenase inhibitor) significantly blunted only A23187-induced vasodilation, while 18α-glycyrrhetinic acid (gap-junction inhibitor) attenuated only acetylcholine-induced vasodilation. These results suggest that the endothelium in mouse mesenteric arteries regulates vascular tone by prostanoids, EDHF, and partially by nitric oxide, different from the endothelium of rat mesenteric arteries.

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Section: Discussionsupporting

confidence: 85%

Section: A23187 (Nmol)mentioning

confidence: 90%

Section: A23187 (Nmol)mentioning

confidence: 90%

Section: A23187 (Nmol)mentioning

confidence: 97%

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Endothelium-Derived Relaxing Factor–Mediated Vasodilation in Mouse Mesenteric Vascular Beds

et al. 2012

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“…With other factors equal, an increase in SMC membrane area would require larger endothelium-derived ionic currents to evoke the same change in SMC membrane potential. The increased requirement for current flow in SMCs from the aged could produce attenuated endotheliumdependent hyperpolarization, contributing to the impaired endothelium-dependent dilation that accompanies aging (25,30). Increased SMC capacitance also would be expected to attenuate the transmission of electrical signals along the vessel and contribute to impairment of conducted (ascending) vasodilation of feed arteries (19).…”

Section: Discussionmentioning

confidence: 99%

Aging increases capacitance and spontaneous transient outward current amplitude of smooth muscle cells from murine superior epigastric arteries

Hayoz

Bradley

Boerman

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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Large conductance Ca(2+)-activated K(+) channels (BKCa) contribute to negative feedback regulation of smooth muscle cell (SMC) tone. However, the effects of aging on BKCa function are unclear. We tested the hypothesis that aging alters SMC BKCa function in superior epigastric arteries (SEAs) by using perforated patch recording of enzymatically isolated SMCs from 3- to 4-mo-old male C57BL/6 mice (Young) and 24- to 26-mo-old male C57BL/6 mice (Old). SMC capacitance from Young (15.7 ± 0.4 pF; n = 110) was less than Old (17.9 ± 0.5 pF; n = 104) (P < 0.05). SMCs displayed spontaneous transient outward currents (STOCs) at membrane potentials more positive than -30 mV; depolarization increased STOC amplitude and frequency (P < 0.05; n = 19-24). STOC frequency in Young (2.2 ± 0.6 Hz) was less than Old (4.2 ± 0.7 Hz) at -10 mV (P < 0.05, n = 27-30), with no difference in amplitude (1.0 ± 0.1 vs. 0.9 ± 0.1 pA/pF, respectively). At +30 mV, STOC amplitude in Young (3.2 ± 0.3 pA/pF) was less than Old (5.0 ± 0.5 pA/pF; P < 0.05, n = 61-67) with no difference in frequency (3.9 ± 0.4 vs. 3.2 ± 0.3 Hz, respectively). BKCa blockers (1 μM paxilline, 100 nM iberiotoxin, 1 mM tetraethylammonium) or a ryanodine receptor antagonist (100 μM tetracaine) inhibited STOCs (n ≥ 6; P < 0.05 each). Western blots revealed increased expression of BKCa α-subunit protein in Old. Pressure myography revealed no effect of age on SEA maximal diameter, myogenic tone, or paxilline-induced constriction (n = 10-12; P > 0.05). Enhanced functional expression of SMC BKCa-dependent STOCs in Old may represent an adaptation of resistance arteries to maintain functional integrity.

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Doxorubicin alters G-protein coupled receptor-mediated vasocontraction in rat coronary arteries

Lozahic,

Maddock,

Wheatley

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Doxorubicin (Doxo)-associated cardio-and vasotoxicity has been recognised as a serious complication of cancer chemotherapy. The purpose of this novel paper was to determine the effect of Doxo on G-protein coupled receptor (GPCR)-mediated vasocontraction located on vascular smooth muscle cells.Rat left anterior descending artery segments were incubated for 24 h with 0.5 µM Doxo was applied. The vasocontractile responses by activation of endothelin receptor type A (ET A ) and type B (ET B ), serotonin receptor 1B (5-HT 1B ) and thromboxane A2 prostanoid receptor (TP) were investigated by a sensitive myography using speci c agonists, while the speci city of the GPCR agonists was veri ed by applying selective antagonists (i.e. ET A agonist = 10 -14 -10 -7.5 M endothelin-1 (ET-1); ET A antagonist = 10 µM BQ123; ET B agonists = 10 -14 -10 -7.5 M sarafotoxin 6c (S6c) and ET-1; ET B antagonist = 0.1 µM BQ788; 5-HT 1B agonist = 10 -12 -10 -5.5 M 5-carboxamidotryptamine (5-CT); 5-HT 1B antagonist = 1 µM GR55562; TP agonist = 10 -12 -10 -6.5 M U46619; TP antagonist = 1 µM Seratrodast).Our results show that 0.5 µM Doxo incubation of LAD segments leads to an increased VSMC vasocontraction through the ET B , 5-HT 1B and TP GPCRs, with a 2.2-fold increase in ET B -mediated vasocontraction at 10 -10.5 M S6c, a 2.0-fold increase in 5-HT 1B -mediated vasocontraction at 10 -5.5 M 5-CT, and a 1.3-fold increase in TP-mediated vasocontraction at 10 -6.5 M U46619.Further studies unravelling the involvement of intracellular GPCR signalling pathways will broaden our understanding of the Doxo-induced vasotoxicity, and thus pave the way to mitigate the adverse effects by potential implementation of adjunct therapy options.

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Age-Related Disappearance of the Inhibitory Effect of Vascular Endothelium on Agonist-Induced Vasoconstriction in Rat Mesenteric Vascular Beds

Cited by 10 publications

References 30 publications

Endothelium-Derived Relaxing Factor–Mediated Vasodilation in Mouse Mesenteric Vascular Beds

Endothelium-Derived Relaxing Factor–Mediated Vasodilation in Mouse Mesenteric Vascular Beds

Aging increases capacitance and spontaneous transient outward current amplitude of smooth muscle cells from murine superior epigastric arteries

Doxorubicin alters G-protein coupled receptor-mediated vasocontraction in rat coronary arteries

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