Effect of nitric oxide synthase inhibitors on endothelial [Ca2+]i and microvessel permeability

He, Pingnian; Liu, B.; Curry, F. E.

doi:10.1152/ajpheart.1997.272.1.h176

Cited by 48 publications

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“…It even inhibits agonist-induced permeability increases without altering an agonist-induced increase in endothelial [Ca 2ϩ ] i . While agents like cAMP, cGMP agonist, and eNOS inhibitor regulate permeability downstream from the initial Ca 2ϩ signals (10,11), these modulators do not affect the agonist-induced increases in endothelial [Ca 2ϩ ] i , similar to S1P. However, unlike S1P, these agents alone have no effect on endothelial [Ca 2ϩ ] i .…”

Section: Discussionmentioning

confidence: 96%

Sphingosine-1-phosphate prevents permeability increases via activation of endothelial sphingosine-1-phosphate receptor 1 in rat venules

Zhang

Qian

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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Zhang G, Xu S, Qian Y, He P. Sphingosine-1-phosphate prevents permeability increases via activation of endothelial sphingosine-1-phosphate receptor 1 in rat venules. Am J Physiol Heart Circ Physiol 299: H1494 -H1504, 2010. First published August 20, 2010 doi:10.1152/ajpheart.00462.2010.-Sphingosine-1-phosphate (S1P) has been demonstrated to enhance endothelial barrier function in vivo and in vitro. However, different S1P receptor subtypes have been indicated to play different or even opposing roles in the regulation of vascular barrier function. This study aims to differentiate the roles of endogenous endothelial S1P subtype receptors in the regulation of permeability in intact microvessels using specific receptor agonist and antagonists. Microvessel permeability was measured with hydraulic conductivity (Lp) in individually perfused rat mesenteric venules. S1P-mediated changes in endothelial intracellular Ca 2ϩ concentration ([Ca 2ϩ ]i) was measured in fura-2-loaded venules. Confocal images of fluorescent immunostaining illustrated the spatial expressions of three S1P subtype receptors (S1PR1-3) in rat venules. The application of S1P (1 M) in the presence of S1P R1-3 inhibited platelet-activating factor-or bradykinin-induced permeability increase. This S1P effect was reversed only with a selective S1PR1 antagonist, W-146, and was not affected by S1PR2 or S1PR3 antagonists JTE-013 and CAY-10444, respectively. S1PR1 was also identified as the sole receptor responsible for S1P-mediated increases in endothelial [Ca 2ϩ ]i. S1PR2 or S1PR3 antagonist alone affected neither basal Lp nor platelet-activating factor-induced permeability increase. The selective S1P R1 agonist, SEW-2871, showed similar [Ca 2ϩ ]i and permeability effect to that of S1P. These results indicate that, despite the presence of S1PR1-3 in the intact venules, only the activation of endothelial S1P R1 is responsible for the protective action of S1P on microvessel permeability and that endogenous S1PR2 or S1PR3 did not exhibit functional roles in the regulation of permeability under basal or acutely stimulated conditions. sphingosine-1-phosphate receptors; microvessel permeability; sphingosine-1-phosphate subtype receptor expression; endothelial calcium concentration AN INFLAMMATORY MEDIATOR-INDUCED increase in microvascular permeability, mainly occurring at postcapillary venules, is a critical event, resulting in edema formation, organ dysfunction, and the pathogenesis of many cardiovascular diseases. The increased microvessel permeability-associated endothelial gap formation also serves as the initiating step for the activation of platelets and leukocytes, resulting in platelet/leukocyte aggregate formation and augmented increases in microvessel permeability (12). Identifying an effective strategy to enhance endothelial barrier function and prevent permeability increases is critical for combating a variety of cardiovascular diseases.Sphingosine-1-phosphate (S1P), a biologically active lipid mediator, has been identified as an important regulat...

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Section: Discussionmentioning

confidence: 96%

Sphingosine-1-phosphate prevents permeability increases via activation of endothelial sphingosine-1-phosphate receptor 1 in rat venules

Zhang

Qian

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…Regarding the role of shear stress in microvascular permeability, NO release by endothelial cells has been suggested to be an important mechanism (3). Investigations performed on individually perfused microvessels indicated that L p is decreased by NOS inhibition (12,35,36). However, it also should be noted that the application of NOS inhibitors can induce an increase in leukocyte adhesion to venular endothelium and a subsequent increase in L p in autoperfused capillaries when L-NAME (at a concentration of 100 M) is treated for longer periods of time (20 min) (10).…”

Section: Vascular Proteinmentioning

confidence: 99%

Regulation of capillary hydraulic conductivity in response to an acute change in shear

Kim¹,

Harris²,

Tarbell³

2005

American Journal of Physiology-Heart and Circulatory Physiology

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-The effects of mechanical perturbations (shear stress, pressure) on microvascular permeability primarily have been examined in micropipette-cannulated vessels or in endothelial monolayers in vitro. The objective of this study is to determine whether acute changes in blood flow shear stress might influence measurements of hydraulic conductivity (Lp) in autoperfused microvessels in vivo. Rat mesenteric microvessels were observed via intravital microscopy. Occlusion of a third-order arteriole with a micropipette was used to divert and increase flow through a nonoccluded capillary or fourth-order arteriolar branch. Using the micropipette occlusion technique in autoperfused rather than cannulated capillaries, Landis described how the fluid filtration rate was most rapid in the initial seconds following occlusion, becoming significantly slower in less than 1 min. This was attributed at least in part to the possibility that plasma oncotic pressure could increase with time in an occluded vessel as a result of greater efflux of water than of protein. However, another consideration is that the vessel occlusion includes an abrupt change in flow-induced shear stress and pressure, both of which could have a time-dependent effect on L p .As a microvessel is occluded, blood flow decreases from its basal value to essentially zero. Several studies have shown that transvascular exchange can be affected by a change in perfusion rate (14,17,19,32,33,43). A small-pore model has been proposed as a possible mechanism to account for flow-dependent transport of small solutes in cannulated vessels (32); moreover, there have been several recent studies of shearinduced increases in fluid filtration performed in vitro (3, 6, 37) and in vivo (27,40,41). The mechanism by which shear forces could increase L p appear to be dependent on nitric oxide (NO) (3,15,24). Therefore, when a capillary stops flowing, it might be expected that L p could decline in a matter of seconds as shear-induced production of NO is attenuated.Another mechanical factor associated with microvessel occlusion is the step increase in hydrostatic pressure. For example, when a capillary is occluded at its downstream end, pressure throughout the vessel increases to that of the feeding arteriole. Recent studies (7,38) indicate that a step increase in hydrostatic pressure causes a decrease in L p in what has been called a "sealing effect." However, the time courses of the changes in L p in these studies were over a period of minutes to hours.The effects of shear on L p have been examined previously in micropipette-cannulated vessels or in endothelial monolayers in vitro. The primary objective of the current study was to determine whether acute changes in blood flow shear might influence measurements of L p in autoperfused, rather than cannulated, microvessels. In addition, a role for NO in shearmediated changes in L p was investigated. MATERIALS AND METHODSAnimal preparation. Animal procedures were approved by an Institutional Animal Care And Use Committee. Male Wistar rats ϳ2...

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“…In the small intestine, NADPH-diaphorase histochemical staining and nNOS immunoreactivity (nNOS-IR) have been demonstrated in perivascular nerves (34,35,41,49), but isoform-specific localization of NOS within the amphibian mesenteric vasculature has not been performed. There is evidence in amphibians that NO is involved in capillary fluid regulation, inasmuch as inhibition of NOS has been reported to decrease hydraulic conductivity (55) and capillary permeability (23,24,54) in the mesenteric circulation of the leopard frog Rana pipiens. Furthermore, substance P (SP) increased microvascular permeability in R. pipiens by increasing NO production (44).…”

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confidence: 99%

Mechanisms of nitric oxide-mediated, neurogenic vasodilation in mesenteric resistance arteries of toad Bufo marinus

Jennings

Donald

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Jennings BL, Donald JA. Mechanisms of nitric oxide-mediated, neurogenic vasodilation in mesenteric resistance arteries of toad Bufo marinus. Am J Physiol Regul Integr Comp Physiol 298: R767-R775, 2010. First published January 13, 2010 doi:10.1152/ajpregu.00148.2009.-This study determined the role of nitric oxide (NO) in neurogenic vasodilation in mesenteric resistance arteries of the toad Bufo marinus. NO synthase (NOS) was anatomically demonstrated in perivascular nerves, but not in the endothelium. ACh and nicotine caused TTX-sensitive neurogenic vasodilation of mesenteric arteries. The ACh-induced vasodilation was endothelium-independent and was mediated by the NO/ soluble guanylyl cyclase signaling pathway, inasmuch as the vasodilation was blocked by the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and the NOS inhibitors N -nitro-L-arginine methyl ester and N -nitro-L-arginine. Furthermore, the ACh-induced vasodilation was significantly decreased by the more selective neural NOS inhibitor N 5 -(1-imino-3-butenyl)-L-ornithine. The nicotine-induced vasodilation was endothelium-independent and mediated by NO and calcitonin gene-related peptide (CGRP), inasmuch as pretreatment of mesenteric arteries with a combination of N -nitro-L-arginine and the CGRP receptor antagonist CGRP-(8 -37) blocked the vasodilation. Clotrimazole significantly decreased the ACh-induced response, providing evidence that a component of the NO vasodilation involved Ca 2ϩ -activated K ϩ or voltage-gated K ϩ channels. These data show that NO control of mesenteric resistance arteries of toad is provided by nitrergic nerves, rather than the endothelium, and implicate NO as a potentially important regulator of gut blood flow and peripheral blood pressure.amphibian; autonomic nervous system; nitric oxide synthase; endothelium IN THE MAMMALIAN MESENTERIC vasculature, it is well established that the endothelium releases numerous vasoactive molecules, such as nitric oxide (NO), prostaglandins, endothelium-derived hyperpolarizing factor (EDHF), and endothelium-derived contracting factors, which contribute to the regulation of vascular tone (26). In addition, mesenteric arteries are innervated by sympathetic vasoconstrictor and primary sensory vasodilator nerves (71). NO is clearly important in maintaining the vasodilator tone of mesenteric arteries, inasmuch as inhibition of NO synthase (NOS) causes vasoconstriction and increases blood pressure (20). Endothelial NOS (eNOS) is the predominant isoform responsible for NO generation in mesenteric arteries, but there is also evidence that neural NOS (nNOS) in perivascular nitrergic nerves generates NO to provide neurally derived vasodilation (2,31,63,66). In contrast to mammals, much less is known about the role of NO in the regulation of mesenteric vascular tone in amphibians. In the small intestine, NADPH-diaphorase histochemical staining and nNOS immunoreactivity (nNOS-IR) have been demonstrated in perivascular nerves (34,35,41,49), but isoform-specific localizati...

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Effect of nitric oxide synthase inhibitors on endothelial [Ca2+]i and microvessel permeability

Cited by 48 publications

References 0 publications

Sphingosine-1-phosphate prevents permeability increases via activation of endothelial sphingosine-1-phosphate receptor 1 in rat venules

Sphingosine-1-phosphate prevents permeability increases via activation of endothelial sphingosine-1-phosphate receptor 1 in rat venules

Regulation of capillary hydraulic conductivity in response to an acute change in shear

Mechanisms of nitric oxide-mediated, neurogenic vasodilation in mesenteric resistance arteries of toad Bufo marinus

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