Characteristics of heterogeneity in the expression of vasoconstriction in response to NG-monomethyl-l-arginine in isolated canine arteries

Kikkawa, Kohei; Hoshino, Tomoko; Yamauchi-Kohno, Rikako; Murata, Shigeru

doi:10.1016/s0014-2999(99)00510-5

Cited by 5 publications

(7 citation statements)

References 44 publications

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“…Other published papers on the effects of N-Arg or N-monomethylarginine administration to resting arteries in vitro show contraction and tend to conclude that endothelial NOS is essentially involved [71, 72]. When the comparison was made, the cerebral arteries were shown to have greater reactivity than peripheral arteries [72, 73], which was also the case in our experiments. The specific influence of sympathectomy on this contractile response seems not to have been previously studied.…”

Section: Discussionsupporting

confidence: 73%

Sympathectomy Causes Aggravated Lesions and Dedifferentiation in Large Rabbit Atherosclerotic Arteries without Involving Nitric Oxide

Kacem¹,

Sercombe²,

Hammami

et al. 2006

J Vasc Res

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Previously [Histochem J 1997;29:279–286], we found that sympathectomy induced neointima formation in ear but not cerebral arteries of genetically hyperlipidemic rabbits. To clarify the influence of sympathetic nerves in atherosclerosis, and whether their influence involves vascular NO activity, we studied groups of normocholesterolemic intact (NI) and sympathectomized (NS), and hypercholesterolemic intact (HI) and sympathectomized (HS) rabbits (diet/6-hydroxydopamine for 79 days). Segments of basilar (BA) and femoral (FA) arteries were studied histochemically, to evaluate differentiation (anti-desmin, anti-vimentin, anti-h-caldesmon, and nuclear dye), by confocal microscopy, and by in vitro myography. In BAs, staining of NI and NS groups was similar. In hypercholesterolemic groups, a small neointima developed, more frequently in HS segments where smooth muscle cells (SMCs) positive for all antibodies appeared to be migrating into the neointima. In FAs, SMCs stained for the three antibodies in the NI group, but we observed desmin- and h-caldesmon-negative, vimentin-positive cells in some external medial layers of the NS, HI and HS groups, identical to adventitial fibroblasts. Large neointimas of the HS group contained vimentin-positive and largely desmin- and h-caldesmon-negative cells. Relaxation of BA or FA segments to acetylcholine was not decreased by sympathectomy. Sympathectomy increased the contraction of resting FAs to nitro-L-arginine (p = 0.0379). Thus, sympathectomy aggravates the tendency for FA SMCs to migrate and dedifferentiate, increasing atherosclerotic lesions, without decreasing NO activity, but has only minor effects on BAs.

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Section: Discussionsupporting

confidence: 73%

Sympathectomy Causes Aggravated Lesions and Dedifferentiation in Large Rabbit Atherosclerotic Arteries without Involving Nitric Oxide

Kacem¹,

Sercombe²,

Hammami

et al. 2006

J Vasc Res

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“…Blood vessels from different sites of the circulation appear to differ in their ability to produce NO when unstimulated, characterized by their vasoconstrictor responses to NOS inhibitors [46]. For example, unstimulated rat aorta does not constrict to l-NOARG and our previous studies [47] examining the effects of chylomicron remnants on isolated rat aorta failed to reveal an inhibitory effect on basal production of NO.…”

Section: Discussionmentioning

confidence: 91%

Chylomicron-remnant-like particles inhibit the basal nitric oxide pathway in porcine coronary artery and aortic endothelial cells

et al. 2003

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The effects of chylomicron remnants on the activity of basally produced nitric oxide (NO) from porcine coronary artery rings and porcine aortic endothelial cells were studied by investigating the effects of chylomicron-remnant-like particles (CMR-LPs) containing porcine apolipoprotein E on the vessel tone of porcine coronary arteries and on cGMP release by aortic endothelial cells. CMR-LPs were oxidized by incubation with CuSO(4) (10 microM) for 18 h at 37 degrees C. N (omega)-nitro-L-arginine (L-NOARG) and oxidized CMR-LPs (oxCMR-LPs), but not native CMR-LPs, increased the vessel tone of static porcine coronary artery rings (increase in tone as a percentage of the tone induced by depolarizing Krebs-Henseleit solution: L-NOARG, 14.24 +/- 2.09; oxCMR-LPs, 4.98 +/- 0.88; and native CMR-LPs, 0.47 +/- 0.21). L-NOARG, endothelium removal and oxCMR-LPs also all significantly increased the maximum relaxation of the vessels to S -nitroso- N -acetyl-DL-penicillamine. In addition, oxCMR-LPs reduced the amounts of cGMP released by porcine aortic endothelial cells into the culture medium from 116 +/- 12.0 to 84.2 +/- 11.6 fmol/microg of cellular protein, mimicking the effects of L-NOARG. These results indicate that oxCMR-LPs, but not native CMR-LPs, inhibit the activity, production or release of NO from unstimulated porcine coronary and aortic endothelial cells. oxCMR-LPs mimicked the addition of L-NOARG and endothelium removal in these experimental systems, suggesting that the lipoproteins were interfering with the L-arginine/NO pathway. This study provides further evidence to support a role of chylomicron remnants in the development of atherosclerosis.

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“…Brain stem slices were equilibrated for 20 minutes in warmed and oxygenated Krebs solution and then stimulated for 10 minutes with BAY 41-2272 (0.1 mol/L), GTN (10 mol/L), forskolin (1 mol/ L), or their combination in the absence or presence of 1H- [1,2,4] oxadiazolo [4,3,-a]quinoxalin-1-one (ODQ; 0 mol/L). Preparations were collected immediately by freezing the segments in liquid nitrogen.…”

Section: Cyclic Nucleotide Levelsmentioning

confidence: 99%

“…[1][2][3] Physiologically, NO is produced by NO synthase (NOS) present in the endothelium (eNOS) and nerves (nNOS) to maintain a basal cerebrovasodilator tone. Conversely, inhibitors of NOS constrict cerebral arteries in vitro 4,5 and decrease cerebral blood flow in vivo. 6,7 NO promotes relaxation of the vascular smooth muscle of cerebral arteries through stimulation of soluble guanylyl cyclase (sGC).…”

mentioning

confidence: 99%

Vasorelaxing Effect of BAY 41-2272 in Rat Basilar Artery

et al. 2006

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Abstract-Decreases in intrinsic NO cause cerebral vasospasms because of the dysregulation of cGMP formation by NO-mediated pathways. Because 5-cyclopropyl-2-{1-(2-fluorobenzyl)-1H-pyrazolo [3,4-b]pyridin-3-yl}pyrimidin-4-ylamine (BAY 41-2272) is a potent soluble guanylyl cyclase (sGC) stimulator in an NO-independent manner, this study aimed to investigate the mechanisms underlying the relaxant effects of BAY 41-2272 in the rat basilar artery. Key Words: nitric oxide Ⅲ cyclic GMP Ⅲ nitric oxide synthase N itric oxide (NO) derived from perivascular nerve fibers and endothelial cells acts as vasodilator for the smooth muscle in the wall of cerebral arteries and, hence, plays an essential role in the regulation of cerebral blood flow under physiological and pathological conditions. 1-3 Physiologically, NO is produced by NO synthase (NOS) present in the endothelium (eNOS) and nerves (nNOS) to maintain a basal cerebrovasodilator tone. Conversely, inhibitors of NOS constrict cerebral arteries in vitro 4,5 and decrease cerebral blood flow in vivo. 6,7 NO promotes relaxation of the vascular smooth muscle of cerebral arteries through stimulation of soluble guanylyl cyclase (sGC). 8 -10 The binding of NO to the heme portion of the enzyme results in cGMP accumulation, which causes smooth muscle relaxation via different mechanisms, including activation of K ϩ channels, desensitization of the contractile proteins, and reduction in intracellular Ca 2ϩ concentration. 11 Impairment of NO-mediated vasodilation accounts for the pathogenesis of cerebral vasospasm. 12,13 Indeed, an inappropriate activation of sGC has been linked to various pathological conditions affecting the cardiovascular system. 14 Although the administration of NO donors to rats with stroke causes brain cGMP levels to increase, induces cell genesis, and improves functional recovery, 15 there are certain disadvantages with NO donor-based therapies, such as the unpredictable pharmacokinetics of NO, development of tolerance, and peroxinitrite formation that can lead to protein S-nitrosylation, as well as tyrosine nitration. 16 -18 Therefore, compounds that activate sGC in an NO-independent manner represent a promising therapeutic strategy.The non-NO-based pyrazolopyridine 5-cyclopropyl-2-{1-(2-fluorobenzyl)-1H-pyrazolo [3,4-b]pyridin-3-yl}pyrimidin-4-ylamine (BAY 41-2272) represents a new therapeutic principle that directly stimulates sGC and increases the sensitivity of the enzyme to NO. 19 This is the primary mechanism through which BAY 41-2272 produces antiplatelet activity, strong decreases in blood pressure, and vasorelaxation. 19,20 This study was designed to identify the mechanisms involved in the relaxations of rat basilar artery induced by BAY 41-2272. We also sought to test the hypothesis that direct stimulation of sGC by BAY 41-2272 relaxes this vessel in a synergistic fashion with endogenous NO.

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Characteristics of heterogeneity in the expression of vasoconstriction in response to NG-monomethyl-l-arginine in isolated canine arteries

Cited by 5 publications

References 44 publications

Sympathectomy Causes Aggravated Lesions and Dedifferentiation in Large Rabbit Atherosclerotic Arteries without Involving Nitric Oxide

Sympathectomy Causes Aggravated Lesions and Dedifferentiation in Large Rabbit Atherosclerotic Arteries without Involving Nitric Oxide

Chylomicron-remnant-like particles inhibit the basal nitric oxide pathway in porcine coronary artery and aortic endothelial cells

Vasorelaxing Effect of BAY 41-2272 in Rat Basilar Artery

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