Enhanced formation of PGI2, a potent hypotensive substance, by aortic rings and homogenates of the spontaneously hypertensive rat

Pace-Asciak, Cecil R.; Carrara, M.C.; Rangaraj, Godha; Nicolaou, K. C.

doi:10.1016/0090-6980(78)90043-6

Cited by 141 publications

(33 citation statements)

References 9 publications

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“…50 Additionally, arteries from spontaneously hypertensive rats have an enhanced capacity (compared to normal tissue) to convert arachidonic acid to PG^, 33 presumably as a consequence of greater mechanical stress. To clarify the effects of blood pressure and flow on PGI 2 production, Eldor et al 4 analyzed canine venous segments transplanted for 6 weeks into the arterial circulation and noted no significant difference in spontaneous and arachidonatestimulated PGI 2 synthesis between arterialized venous autografts and control veins.…”

Section: Resultsmentioning

confidence: 99%

Regional variability of prostacyclin biosynthesis.

et al. 1989

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To Investigate the regional variability In arterial and venous endothellal prostacyclin (PGIj) biosynthesis, we obtained 1-cm segments of carotid arteries, external jugular veins, femoral arteries and veins, lilac arteries and veins, Inferior venae cavae (IVC), and aortas from 17 dogs. Vessel lumlnal PGI 2 production was measured In the basal state by radlolmmunoassay of 6-keto-prostaglandln F 1o (6-keto-PGF 1a ). A total of 90 arterial specimens (57, 19, and 14 segments, respectively, of femoral/carotid arteries, lilac arteries, and aorta) and 41 venous specimens (15,10, and 16 segments, respectively, of femoral/jugular veins, lilac veins, and IVC) were analyzed. Overall, arterial endothellal 6-keto-PGF 1a was higher than venous (8.1 ±0.5 ng/ml vs. 4.9±0.7 ng/ml, p<0.0004); 6-keto-PGF 1a levels were greater In the arteries than In their corresponding veins [femoral/carotid arteries (6.3±0.4 ng/ml) vs. femoral/jugular vein (2.1 ±0.4 ng/ml), /xO.0002; Iliac arteries (9.3±1.0 ng/ml) vs. iliac veins (4.8±0.9 ng/ml), /xO.005; aorta (14.0±1.6 ng/ml) vs. IVC (

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Section: Resultsmentioning

confidence: 99%

Regional variability of prostacyclin biosynthesis.

et al. 1989

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“…The technique that we have used to assess prostaglandin production by the arterial tissue has several advantages as compared with arterial strips or rings that have been conventionally used (26,27). First, this technique is more physiological in that it allows us to assay the activity of prostaglandin at the luminal surface of the vessel wall where these substances affect on the endothelial surface.…”

Section: Discussionmentioning

confidence: 99%

Recovery of prostacyclin production by de-endothelialized rabbit aorta. Critical role of neointimal smooth muscle cells.

Eldor¹,

Falcone²,

Hajjar³

et al. 1981

J. Clin. Invest.

165

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A B S T R A C T Prostacyclin (PGI2) synthetic capacity was assayed at the surface of aortas at various intervals after removal of endothelium with a balloon catheter. Results were correlated with morphologic changes in the vessel wall seen by light microscopy, scanning and transmission electron microscopy. To assay PGI2 synthetic capacity, we applied an incubation chamber to the luminal surface of the aortas; after arachidonic acid stimulation we assayed the PGI2 synthesized with a bioassay and radioimmunoassay. PGI2 synthesis in deendothelialized aortas was determined immediately after balloon-catheter injury and at intervals of 1 h and 2, 4, 15, 35, and 70 d. PGI2 synthesis was low at 1 h and increased over time with levels at 35 and 70 d reaching that of normal artery. Scanning and transmission electron microscopy of de-endothelialized areas showed persistent absence of endothelium with formation of a neointima composed of smooth muscle cells. De-endothelialized aorta was covered with adherent platelets shortly after injury, however several days later only a few platelets adhered to the denuded surface.Results indicated that (a) endothelium is responsible for nearly all PGI2 production at the luminal surface of the normal aorta, (b) de-endothelialized muscular neointima synthesized increasing quantities of PGI2 with time after injury, and (c) increase of PGI2

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“…Other researchers, however, have reported that PI turnover is enhanced and cytosolic calcium level may be increased in various tissues in spontaneously hypertensive rats (SHR) (11,(19)(20)(21)(22) . SHR have also been found to have enhanced prostaglandin synthesis in their vascular walls and kidneys (23)(24)(25). There is, therefore, an apparent discrepancy in cytosolic calcium metabolism between the two genetic models of hypertensive rats.…”

Section: Discussionmentioning

confidence: 99%

Alterations in Receptor-Mediated Activation of Phospholipase A2 in DAHL Salt-Sensitive Rats.

et al. 1993

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In this study, the subcellular mechanism of impaired prostacyclin (PGI2) synthesis in the vascular system of Dahl salt-sensitive (Dahl S) rats was investigated.Arachidonate liberation in response to PDGF or bradykinin was decreased in cultured aortic smooth muscle cell (VSMC) from Dahl S rats, compared with Dahl salt-resistant (Dahl R) rats. Phospholipase C (PIP2-PLC) activity was lowered and the inositol 1,4,5-triphosphate content was also decreased in the VSMC from Dahl S rats. In fact, cytosolic calcium levels in basal and angiotensin-II stimulated conditions were significantly decreased in VSMC from Dahl S rats, compared with those in Dahl rats. There was no difference, however, in phospholipase A2 (PLA2) activity in the two strains. Moreover, the PLA2 enzyme properties, e.g., its Ca2+ requirement, pH profile, Km value and Vmax, were equal in Dahl S and Dahl R rats. The level of functional PLA2 messenger RNA was found to be greater in the VSMC from Dahl S rats. Similarly, PGI2 synthesis was reduced in Dahl S rats and this was associated with an unaltered PLA2 concentration and decreased PIP2-PLC activity in the arterial wall. Thus, these data indicate that dysfunction of receptor-mediated PLA2 activation is responsible for altered PGI2 synthesis in Dahl S rats. This finding is likely mediated by a decrease in phosphoinositides metabolism. (Hypertens Res 1993 ;16 :105-111) Key Words: Dahl salt-sensitive rats, smooth muscle cell, phospholipase A2, phosphoinositide metabolism, phospholipase CThe potential role of prostaglandins in the genesis of hypertension has generated considerable research interest. Evidence has accumulated which suggests that impaired vasodepressor prostaglandin system can contribute to the development of hypertension in Dahl salt-sensitive (Dahl S) rats. Restoration of prostaglandin synthesis by linoloate-rich diet can lead to attenuation of hypertension in Dahl S rats (1-4). Few studies, however, have addressed the cause of impaired prostaglandin synthesis at a subcellular level in Dahl S rats. In a recent study, Craven et al. (5) have reported that a decrease in vasopressin-stimulated prostaglandin synthesis occurs in the renomedullary interstitial cells and that it is associated with a decrease in the receptormediated cytosolic calcium level (5, 6). Since phospholipase A2 (PLA2) and phospholipase C (PLC) are coupled with receptors and GTP-binding proteins and release free arachidonic acid, they may be rate limiting for prostaglandin synthesis.To understand the abnormal response of the prostaglandin system in Dahl S rats, we have examined PLA2, a key component in prostaglandin biosynthesis. We report in this study an investigation of the enzyme kinetic parameters and altered regulation of PLA2, using cultured aortic smooth muscle cells (VSMC) and the arterial wall from Dahl S rats.Materials and Methods Experiment 1. Cell Culture Dahl S and Dahl salt-resistant (Dahi R) rats were originally obtained from Brookhaven National Laboratory, Upton, New York and bred at Tsukuba Research Labo...

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Enhanced formation of PGI2, a potent hypotensive substance, by aortic rings and homogenates of the spontaneously hypertensive rat

Cited by 141 publications

References 9 publications

Regional variability of prostacyclin biosynthesis.

Regional variability of prostacyclin biosynthesis.

Recovery of prostacyclin production by de-endothelialized rabbit aorta. Critical role of neointimal smooth muscle cells.

Alterations in Receptor-Mediated Activation of Phospholipase A2 in DAHL Salt-Sensitive Rats.

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