Different patterns of release of endothelium‐derived relaxing factor and prostacyclin

Mitchell, Jane A.; Nucci, Gilberto De; Warner, Timothy D.; Vane, John R.

doi:10.1111/j.1476-5381.1992.tb14280.x

Cited by 39 publications

(23 citation statements)

References 36 publications

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“…Responses to the vasoconstrictors phenylephrine (α 1 -adrenoceptor agonist) and U46619 (thromboxane A 2 mimetic) were identical in vessels taken from WT and ecCNP KO animals regardless of sex (Supplemental Figure 1, A-H; supplemental material available online with this article; doi:10.1172/JCI74281DS1). In the aorta, the endothelium-dependent dilator acetylcholine (ACh) produced concentration-dependent relaxations of both WT and ecCNP KO tissues with analogous potency and efficacy, albeit with a small reduction in maximal relaxation in the female ecCNP KO mice ( Figure 2, A and E); these data are in accord with previous work establishing that such relaxations are primarily dependent on the release of endothelium-derived NO and PGI 2 (20). In marked contrast, in mesenteric small arteries, there was a significant rightward shift (indicative of decreased potency) in the vasorelaxant concentration-response curve to ACh in female ( Figure 2F), but not male ( Figure 2B), vessels.…”

Section: Resultssupporting

confidence: 82%

Endothelial C-type natriuretic peptide maintains vascular homeostasis

Moyes¹,

Khambata²,

Villar³

et al. 2014

J. Clin. Invest.

141

139

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Section: Resultssupporting

confidence: 82%

Endothelial C-type natriuretic peptide maintains vascular homeostasis

Moyes¹,

Khambata²,

Villar³

et al. 2014

J. Clin. Invest.

141

139

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“…This suggested to us that NO release by the endothelium was responsible for the sustained dilation we observed. This observation is consistent with what we know about endothelial-derived NO from larger vessels or from cultured endothelial cells (27). Furthermore, the release of NO from the endothelium in vivo is also occurring in a sustained manner, since the administration of NOS inhibitors produces an immediate increase in blood pressure (34), akin to the reversal of dilator response we see in our study.…”

Section: Discussionsupporting

confidence: 80%

“…Our observations raised the following question: if L-NAME, but not TRAM-34 plus apamin, could fully reverse the dilator responses we see with acetylcholine in these vessels, where is the EDHF? Perhaps EDHF, like another important vasoactive hormone, prostacyclin, could be released by the endothelium in a transient manner (25,27) under conditions where endothelial-derived NO is released in a sustained fashion (27). To test this possibility, we pretreated mesenteric arteries with L-NAME to block NOSIII pharmacologically, or we used vessels from NOSIII Ϫ/Ϫ mice and repeated our protocols where acetylcholine was added at a maximal concentration to preconstricted vessels.…”

Section: Discussionmentioning

confidence: 99%

“…The temporal nature of EDHF is not well described, although a limited number of papers from the late 1980s and early 1990s show that EDHF is either transient (15,24,37) or sustained (7,14), depending on the vessel type studied. In contrast, there is clear consensus that NO is released continually by activated endothelium (27,34) via the enzyme nitric oxide synthase (NOS)III (20).…”

mentioning

confidence: 99%

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Elucidation of the temporal relationship between endothelial-derived NO and EDHF in mesenteric vessels

Harrington¹,

Carrier²,

Gallagher³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Although the endothelium co-generates both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), the relative contribution from each vasodilator is not clear. In studies where the endothelium is stimulated acutely, EDHF responses predominate in small arteries. However, the temporal relationship between endothelial-derived NO and EDHF over more prolonged periods is unclear but of major physiological importance. Here we have used a classical pharmacological approach to show that EDHF is released transiently compared with NO. Acetylcholine (3 ϫ 10 Ϫ6 mol/l) dilated second-and/or thirdorder mesenteric arteries for prolonged periods of up to 1 h, an effect that was reversed fully and immediately by the subsequent addition of L-NAME (10 Ϫ3 mol/l) but not TRAM-34 (10 Ϫ6 mol/l) plus apamin (5 ϫ 10 Ϫ7 mol/l). When vessels were pretreated with L-NAME, acetylcholine induced relatively transient dilator responses (declining over ϳ5 min), and vessels were sensitive to TRAM-34 plus apamin. When measured in parallel, the dilator effects of acetylcholine outlasted the smooth muscle hyperpolarization. However, in the presence of L-NAME, vasodilatation and hyperpolarization followed an identical time course. In vessels from NOSIII Ϫ/Ϫ mice, acetylcholine induced small but detectable dilator responses that were transient in duration and blocked by TRAM-34 plus apamin. EDHF responses in these mouse arteries were inhibited by an intracellular calcium blocker, TMB-8, and the phospholipase A 2 inhibitor AACOCF3, suggesting a role for lipid metabolites. These data show for the first time that EDHF is released transiently, whereas endothelial-derived NO is released in a sustained manner.arteries; vasodilation; mediators; hyperpolarization; nitric oxide; endothelium-derived hyperpolarizing factor THE ENDOTHELIUM-DERIVED relaxing factor, described in 1980 by Furchgott and Zawadozki (18), is now known to be nitric oxide (NO) (22, 23), formed from the amino acid L-arginine (32). In 1988, reports emerged of a distinct factor released by the endothelium that relaxed blood vessels via a process of hyperpolarization (endothelium-derived hyperpolarizing factor; EDHF) (2,3,15). Since this time, EDHF biology has developed at a rapid pace (9). However, there is still considerable debate about the identity of EDHF. Potential candidates include CYP450 metabolites (17), K ϩ (16), hydrogen peroxide (26), and K ϩ and/or electrical communications through gap junctions (39) and possibly C-type natriuretic peptide (CNP) (13).Much of the evidence supporting a role for EDHF in endothelium-dependent dilation has been derived pharmacologically, for example, by removing other dilatory pathways (NO and prostacyclin), removing the endothelium, removing the ability to hyperpolarize (with high [K ϩ ]), or blocking K ϩ channels with agents such as TRAM-34 plus apamin. Usually, experiments are conducted where the vessels are stimulated acutely and the responses monitored for short periods of time (seconds or minutes). The temporal nature of EDHF is...

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“…NO is released from endothelial cells continuously while cells are activated 90,91) and, owing to the high Ca 2＋ sensitivity of CaM, NO is up-regulated rapidly in response to increases in shear stress 92,93) . In healthy arteries, NO is therefore important for maintaining basal tone, as well as regulating tone in response to short-term increases in shear stress 94) .…”

Section: Response To Shear Stressmentioning

confidence: 99%

There^|^rsquo;s More to Flow-Mediated Dilation Than Nitric Oxide

Stoner

Erickson

Young³

et al. 2012

JAT

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Flow-mediated dilation (FMD) is the standard tool used to assess endothelial function. The premise behind the standard FMD test is that it serves as an endothelial-dependant nitric oxide bioassay; however, the endothelium may release additional dilatory molecules which contribute to FMD, most notably prostacyclin and endothelial-derived hyperpolarizing factor. The relative importance of these molecules to the dilatory response may vary substantially among individuals, particularly in response to a number of diseased states. This review discusses how each of these molecules may contribute to vasodilation, and considers the circumstances in which they may vary.

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Different patterns of release of endothelium‐derived relaxing factor and prostacyclin

Cited by 39 publications

References 36 publications

Endothelial C-type natriuretic peptide maintains vascular homeostasis

Endothelial C-type natriuretic peptide maintains vascular homeostasis

Elucidation of the temporal relationship between endothelial-derived NO and EDHF in mesenteric vessels

There^|^rsquo;s More to Flow-Mediated Dilation Than Nitric Oxide

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