The generation of prostacyclin by arteries and by the coronary vascular bed is reduced in experimental atherosclerosis in rabbits

Dembińska-Kieć, A.; Gryglewska, T.; Zmuda, A; Gryglewski, Ryszard J.

doi:10.1016/0090-6980(77)90282-9

Cited by 267 publications

(24 citation statements)

References 31 publications

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“…Whether COX-2 is also overexpressed in SHR rats remains to be tested. In rabbits, a hypercholesterolemic diet as short as 4 weeks led to the substantial inhibition of PGI 2 production (Dembinska-Kiec et al, 1977). In SHR or in WKY rats, a hypercholesterolemic diet lasting 12 weeks did not influence vascular PGI 2 production.…”

Section: Discussionmentioning

confidence: 84%

Hypercholesterolemia Does Not Alter Endothelial Function in Spontaneously Hypertensive Rats

Lorkowska¹,

Bartuś²,

Franczyk³

et al. 2006

J Pharmacol Exp Ther

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In humans, hypercholesterolemia and hypertension are associated with endothelial dysfunction. Here, we assess whether hypercholesterolemia induces endothelial dysfunction in rats with pre-existing hypertension. Spontaneously hypertensive rats (SHR) and normotensive controls (WKY) were fed with a high-cholesterol diet for 12 weeks, and endothelial function was assessed in isolated thoracic aortic rings. In SHR and WKY rats, the hypercholesterolemic diet resulted in the elevation of total cholesterol and low-density lipoprotein levels by approximately 2.5-and 4.5-fold, respectively. However, in aorta, the basal nitric oxide (NO) production-as assessed by the magnitude of L-N G -nitroarginine methyl ester-induced vasoconstriction as well as the NO-dependent relaxation induced by acetylcholine or histamine-were not diminished either in SHR or in WKY rats fed with the hypercholesterolemic diet. Interestingly, prostacyclin (PGI 2 ) production in aortic rings from SHR rats was higher than in the aorta from WKY rats. However, the hypercholesterolemic diet had no further effects on PGI 2 production in the aorta either of SHR or WKY rats. The monocyte chemoattractant protein 1 level in plasma was slightly elevated in SHR and WKY rats fed with the hypercholesterolemic diet compared with their normocholesterolemic counterparts. In summary, even in the presence of pre-existing hypertension, hypercholesterolemia fails to modify NO-dependent and PGI 2 -dependent endothelial function in SHR rats; it also does not induce a robust inflammatory response. Both are prerequisites for the development of atherosclerosis.

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Section: Discussionmentioning

confidence: 84%

Hypercholesterolemia Does Not Alter Endothelial Function in Spontaneously Hypertensive Rats

Lorkowska¹,

Bartuś²,

Franczyk³

et al. 2006

J Pharmacol Exp Ther

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“…The majority of observations suggest that biosynthesis of eicosanoids is reduced in arteriosclerotic vessels. Initially, Dembinska-Kiec et al 20 reported that experimental arteriosclerosis was associated with a suppression of prostacyclin generation in mesenteric rings. Other decreases in PG production were subsequently shown in human umbilical vein endothelium, 21 whole-vessel aorta, 22 aortic microvessels, 23 renal microvessels, 24 human hepatocellular carcinoma cells, 25 rabbit platelets, 26 and macrophages.…”

Section: Discussionmentioning

confidence: 99%

25-Hydroxycholesterol Increases Eicosanoids and Alters Morphology in Cultured Pulmonary Artery Smooth Muscle and Endothelial Cells

Wohlfeil

Campbell

1999

ATVB

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Abstract-25-Hydroxycholesterol (25-OHC) is an oxidized derivative of cholesterol that has been implicated in the early development of arteriosclerosis. Changes in arterial smooth muscle cell (SMC) migration and proliferation have also been linked to the pathophysiology of arteriosclerosis. SMCs undergo "activation" in response to vascular injury by changing phenotypically and by increasing prostaglandin G/H synthase-2 (PGHS-2) protein levels and eicosanoid release. Activation is thought to be important in atheroma formation and arteriosclerosis progression. 25-OHC induces SMCs to change morphologically, increase PGHS-2, and increase eicosanoid release. Confluent monolayers were treated with 25-OHC (10 g/mL) or the PGHS-2 inducer interleukin-1␤ (1 ng/mL) for 18 hours at 37°C. The 18-hour treatment resulted in morphological changes. After uptake of [ 14 C]arachidonic acid, released radiolabeled arachidonic acid products were extracted and chromatographed by both normal and reverse-phase high-performance liquid chromatography systems. 25-OHC-treated cells increased their prostaglandin production, with the major component comigrating with a prostaglandin-E 2 standard. HETEs and epoxyeicosatrienoic acids were not affected. Immunoprecipitation analysis of treated and control cell lysates using anti-PGHS-1 and -2 and anti-␣-actin primary antibodies indicated PGHS-2 induction over control and no change in contractile proteins. These changes are consistent with SMC activation, which occurs in vascular injury models. The notion that oxysterols can activate vascular SMCs may be important in ultimately understanding the pathophysiology of atheroma formation. (Arterioscler Thromb Vasc Biol. 1999;19

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“…It has been demonstrated that ergotamine stimulates prostaglandin synthesis in canine saphenous veins (30), and that prostacyclin (PGI2) synthesis is suppressed in aortae from cholesterol-fed rabbits (31). Therefore, we have considered the possibility that augmented contractions in response to ergonovine reflected in part a decreased prostacyclin-dependent relaxation of vascular smooth muscle.…”

Section: Discussionmentioning

confidence: 99%

Supersensitivity of Atherosclerotic Rabbit Aorta to Ergonovine

Henry¹,

Yokoyama²

1980

J. Clin. Invest.

268

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A B S T R A C T Patients with coronary vasospasm appear to be supersensitive to the coronary constrictor effects of ergonovine. To determine whether atherosclerosis alters arterial reactivity and sensitizes arteries to ergonovine, contractile responses of isolated aortae from control rabbits and from rabbits fed a highcholesterol diet were compared. Aortic strips were mounted in a myograph for the monitoring of isometric tension, equilibrated in oxygenated Krebs buffer, and exposed to graded concentrations of agonists and antagonists. The concentration-response relation for ergonovine in atherosclerotic arteries exhibited a markedly depressed constrictor threshold concentration (0.5 pM vs. 0.23 uM in controls), a significantly lowered one-half effective dose (ED50) value, and an augmented maximal response. Furthermore, atherosclerotic arteries showed similar, although less pronounced changes in the concentration-response relation for serotonin. In contrast, responses to 34 mM KC1 were virtually identical, and the concentration-response relation for phenylephrine were similar in the two groups. In control arteries, 0.1 ,M phentolamine and 0.1 ,M prazosin suppressed responses to 1 ,uM ergonovine by 71 and 90%, respectively. However, in atherosclerotic arteries a-blockers in the same concentration inhibited responses to 0.01 ,uM ergonovine by less than 10%. On the other hand, 0.1 ,uM cyproheptadine, a serotonergic antagonist, suppressed these responses by 82%. Thus, the supersensitivity to ergonovine appeared to be mediated predominantly by a serotonergic mechanism. These results indicate that smooth muscle in atherosclerotic arteries may be supersensitive to specific vasoconstricting stimuli, a change that might contribute to arterial dysfunction in vivo.

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The generation of prostacyclin by arteries and by the coronary vascular bed is reduced in experimental atherosclerosis in rabbits

Cited by 267 publications

References 31 publications

Hypercholesterolemia Does Not Alter Endothelial Function in Spontaneously Hypertensive Rats

Hypercholesterolemia Does Not Alter Endothelial Function in Spontaneously Hypertensive Rats

25-Hydroxycholesterol Increases Eicosanoids and Alters Morphology in Cultured Pulmonary Artery Smooth Muscle and Endothelial Cells

Supersensitivity of Atherosclerotic Rabbit Aorta to Ergonovine

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