Endothelium‐dependent modulation of pacemaking in lymphatic vessels of the guinea‐pig mesentery.

Weid, Pierre‐Yves von der; Crowe, Melissa; Helden, Dirk F. van

doi:10.1113/jphysiol.1996.sp021404

Cited by 101 publications

(157 citation statements)

References 31 publications

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“…Comparison of these two recordings in Fig. 6, A and B, also indicates that L-NNA treatment slightly increased the frequency of action potentials, consistent with a previous observation that a basal production of NO occurs in these lymphatic vessels (53). Paired experiments on five segments with this inhibitor of NOS reduced the hyperpolarization induced by 100 nM CGRP to a nonsignificant level (Fig.…”

Section: Effect Of Cgrp On Lymphatic Vasomotionsupporting

confidence: 71%

“…Endothelium action occurred through release of NO as the 100 nM CGRP-induced inhibition was completely abolished in the presence of a NOS inhibitor L-NNA, an action that was reversed by the addition of the NO substrate L-arginine. NO is known to strongly regulate spontaneous constrictions in lymphatic vessels, particularly in response to endothelial agonists such as ACh (45,53,59) or shear stress (21).…”

Section: Discussionmentioning

confidence: 99%

“…The lumen was then washed out with low-calcium PSS. This procedure is a slight modification of that used previously (53) where the endothelium from this same tissue was successfully destroyed, as tested both morphologically and pharmacologically. The success of the lysing was tested by a procedure presented in a previous study (53).…”

Section: Lysis Of Endotheliummentioning

confidence: 99%

“…This procedure is a slight modification of that used previously (53) where the endothelium from this same tissue was successfully destroyed, as tested both morphologically and pharmacologically. The success of the lysing was tested by a procedure presented in a previous study (53). Here it was found that whereas in the majority of lymphatic vessels, constrictions were inhibited by both ACh and sodium nitroprusside (SNP), there was a "nonresponding" group that did not respond in any way to either ACh (10 -100 M) or SNP (100 M).…”

Section: Lysis Of Endotheliummentioning

confidence: 99%

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Calcitonin gene-related peptide activates different signaling pathways in mesenteric lymphatics of guinea pigs

Hosaka¹,

Rayner²,

Weid³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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The effects of calcitonin generelated peptide (CGRP) on constriction frequency, smooth muscle membrane potential (V m), and endothelial Vm of guinea pig mesenteric lymphatics were examined in vitro. CGRP (1-100 nM) caused an endothelium-dependent decrease in the constriction frequency of perfused lymphatic vessels. The endothelium-dependent CGRP response was abolished by the CGRP-1 receptor antagonist CGRP-(8 -37) (1 M) and pertussis toxin (100 ng/ml). This action of CGRP was also blocked by the nitric oxide (NO) synthase inhibitor N G -nitro-Larginine (L-NNA; 10 M), an action that was reversed by the addition of L-arginine (100 M). cGMP, adenylate cyclase, cAMP-dependent protein kinase (PKA), and ATP-sensitive K ϩ (K ATP ϩ ) channels were all implicated in the endothelium-dependent CGRP response because it was abolished by methylene blue (20-5-isoquinolinesulfonamide-dichloride (H89; 1 M) and glibenclamide (10 M). CGRP (100 nM), unlike acetylcholine, did not alter endothelial intracellular Ca 2ϩ concentration or V m. CGRP (100 nM) hyperpolarized the smooth muscle Vm, an effect inhibited by L-NNA, H89, or glibenclamide. CGRP (500 nM) also caused a decrease in constriction frequency. However, this was no longer blocked by CGRP-(8 -37). CGRP (500 nM) also caused smooth muscle hyperpolarization, an action that was now not blocked by L-NNA (100 M). It was most likely mediated by the activation of the cAMP/PKA pathway and the opening of K ATP ϩ channels because it was abolished by H89 or glibenclamide. We conclude that CGRP, at low to moderate concentrations (i.e., 1-100 nM), decreases lymphatic constriction frequency primarily by the stimulation of CGRP-1 receptors coupled to pertussis toxin-sensitive G proteins and the release of NO from the endothelium or enhancement of the actions of endogenous NO. At high concentrations (i.e., 500 nM), CGRP also directly activates the smooth muscle independent of NO. Both mechanisms of activation ultimately cause the PKA-mediated opening of K ATP ϩ channels and resultant hyperpolarization. smooth muscle; endothelium; nitric oxide; adenosine 3Ј,5Ј-cyclic monophosphate-dependent protein kinase; vasomotion CALCITONIN GENE-RELATED PEPTIDE (CGRP), like substance P, is a dominant neurotransmitter in vascular sensory nerves and is a potent vasodilator, which may play a role in modulation of total peripheral resistance of the systemic circulation (6,22,30). The pathways by which CGRP produces vasodilation vary between vascular beds. In the majority of blood vessels, application of CGRP has been reported to cause dilation through an endothelium-independent process. These vessels include cat cerebral (16, 48), rat mesenteric (1, 20, 25, 35), rat stomach mucosal (27), rabbit jejunal (34), dog basilar (40), dog lingual (33), and human uterine arteries (5). A primary signal transduction pathway involved in this form of CGRP activation is adenylate cyclase, which increases cAMP and cAMP-dependent protein kinase (PKA)-activating K ϩ channels including ATP-sensitive K ϩ (K ATP ϩ ) channels (37,...

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Section: Effect Of Cgrp On Lymphatic Vasomotionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Lysis Of Endotheliummentioning

confidence: 99%

Section: Lysis Of Endotheliummentioning

confidence: 99%

See 2 more Smart Citations

Calcitonin gene-related peptide activates different signaling pathways in mesenteric lymphatics of guinea pigs

Hosaka¹,

Rayner²,

Weid³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…A reasonably rapid change in solutions could be effected with the latter, with 495% bath changeover in o10 s. In some cases, vessels were luminally perfused (Rayner & van Helden, 1997) at a rate of about 3 ml min À1 to destroy the endothelium, as effected by briefly (5 -10 s) passing air through the vessels some 5 -6 times. The relative success of the lysing procedure was then tested (see von der Weid et al, 1996). Tissues were normally used within 1 -4 h of isolation, and were stored at 41C in physiological saline until used.…”

mentioning

confidence: 99%

ET‐1‐associated vasomotion and vasospasm in lymphatic vessels of the guinea‐pig mesentery

Zhao

Helden

2003

British J Pharmacology

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1 In vitro experiments were performed to investigate the actions of endothelin-1 (ET-1) on vasomotion and vasospasm in guinea-pig mesenteric lymphatics. 2 ET-1 modulated lymphatic vasomotion independent of the endothelium, with lower concentrations (p10 nM) increasing lymphatic vasomotion and higher concentrations (X100 nM) causing vasospasm. 3 ET-1-induced increases in vasomotion were accompanied by an increase in tonic [Ca 2 þ ] i . 4 These actions were inhibited by the ET A receptor antagonist BQ-123 (1 mM), the phospholipase C (PLC) inhibitor U73122 (5 mM), removal of extracellular Ca 2 þ , chelation of intracellular Ca 2 þ with BAPTA/AM (10 mM), the store Ca 2 þ -ATPase inhibitor thapsigargin (1 mM), caffeine (10 mM) and the inositol 1,4,5-trisphosphate (IP 3 ) receptor blocker heparin and 2-APB (30 mM). In contrast, the ET B receptor antagonist BQ-788 (1 mM), ryanodine (1 & 20 mM), pertussis toxin (PTx) or Cs þ had no significant actions on vasomotion or the magnitude of increase in tonic [Ca 2 þ ] i . 5 ET-1-induced vasospasm was accompanied by a transient increase in smooth muscle [Ca 2 þ ] i followed by a sustained plateau, an action that was abolished by removal of extracellular Ca 2 þ , but only marginally inhibited by nifedipine (1 mM). 6 Caffeine (10 mM), SKF 96165 (30 mM) or U73122 (5 mM) together with nifedipine (1 mM) abolished ET-1-induced vasospasm and increase in [Ca 2 þ ] i . 7 These results indicate that ET-1 increases lymphatic vasomotion by acting on smooth muscle ET A receptors and activation of G-protein-PLC-IP 3 cascade, which is known to cause pacemaker Ca 2 þ release and resultant pacemaker potentials. High concentrations of ET-1 cause a failure in Ca 2 þ homeostasis causing vasospasm, triggered by excessive Ca 2 þ influx primarily through store-operated channels (SOCs) with L-Ca 2 þ voltage-operated channels (VOCs) also contributing, but to a much lesser extent.

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Heterogeneous control of blood flow amongst different vascular beds

2000

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The control and maintenance of vascular tone is due to a balance between vasoconstrictor and vasodilator pathways. Vasomotor responses to neural, metabolic and physical factors vary between vessels in different vascular beds, as well as along the same bed, particularly as vessels become smaller. These differences result from variation in the composition of neurotransmitters released by perivascular nerves, variation in the array and activation of receptor subtypes expressed in different vascular beds and variation in the signal transduction pathways activated in either the vascular smooth muscle or endothelial cells. As the study of vasomotor responses often requires pre‐existing tone, some of the reported heterogeneity in the relative contributions of different vasodilator mechanisms may be compounded by different experimental conditions. Biochemical variations, such as the expression of ion channels, connexin subtypes and other important components of second messenger cascades, have been documented in the smooth muscle and endothelial cells in different parts of the body. Anatomical variations, in the presence and prevalence of gap junctions between smooth muscle cells, between endothelial cells and at myoendothelial gap junctions, between the two cell layers, have also been described. These factors will contribute further to the heterogeneity in local and conducted responses. © 2000 John Wiley & Sons, Inc. Med Res Rev, 21, No. 1, 1–60, 2001

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Endothelium‐dependent modulation of pacemaking in lymphatic vessels of the guinea‐pig mesentery.

Cited by 101 publications

References 31 publications

Calcitonin gene-related peptide activates different signaling pathways in mesenteric lymphatics of guinea pigs

Calcitonin gene-related peptide activates different signaling pathways in mesenteric lymphatics of guinea pigs

ET‐1‐associated vasomotion and vasospasm in lymphatic vessels of the guinea‐pig mesentery

Heterogeneous control of blood flow amongst different vascular beds

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