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Decrease in cyclosporin-mediated prostacyclin production in renal versus carotid arteries: a mechanism for cyclosporin-induced hypertension.

E L Hoover·B S Harrison·W W Williams·R Tesi·C Z Adams·W L Weaver·M A McMillen
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Abstract

Although the mechanism of cyclosporin (CsA)-induced hypertension is unknown, it has been shown to inhibit prostacyclin (PGI2) production directly, which may be a factor. We determined whether CsA had a differential effect on PGI2 production from the carotid artery (CA) and internal jugular vein (JV) compared to that from the renal artery (RA) and vein (RV) as a possible contributing factor to renovascular hypertension based upon the ability of organs to regulate their own blood flow according to local circumstances. The neck and renal vessels were removed from anesthetized adult female dogs (N = 8) and placed in a stimulation chamber, with Cell I being control (Hepes buffer), Cell II containing 0.3 mg/ml CsA, and Cell III containing CsA and 25 microM arachidonic acid (AA). Following serial stimulation periods, the supernatant was evaluated for PGI2 production by radioimmunoassay. PGI2 production from CA was significantly higher than that from RA following control and AA stimulation, 1474 +/- 382 pg/cm2-min vs 733 +/- 173 pg/cm2-min (P less than 0.05) and 2236 +/- 347 vs 1090 +/- 217 (P less than 0.01), respectively. CsA-induced PGI2 production from the carotid arteries was significantly greater than that from the renal arteries, 2944 +/- 586 vs 1003 +/- 235 (P less than 0.005). However, stimulation with AA following CsA resulted in sustained PGI2 production in both arteries that was similar to stimulation with CsA alone, 3014 +/- 600 vs 2944 +/- 586 for the carotids and 1278 +/- 280 vs 1003 +/- 235 for the renal arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

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AnimalsArachidonic AcidArachidonic AcidsBiomechanical PhenomenaCarotid ArteriesCyclosporinsDisease Models, AnimalDogsEpoprostenolHypertensionIn Vitro TechniquesJugular VeinsRenal ArteryRenal VeinsJournal ArticleResearch Support, Non-U.S. Gov't

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E L Hoover, B S Harrison, W W Williams, R Tesi, C Z Adams, W L Weaver, M A McMillen. 1990. Decrease in cyclosporin-mediated prostacyclin production in renal versus carotid arteries: a mechanism for cyclosporin-induced hypertension.. https://doi.org/10.1016/0022-4804(90)90017-v

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