(Hypertension. 2001;37:135.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
From the Laboratorium voor Fysiologie (I.M., H.De S., F.W., J.B.P.), KU Leuven, Leuven, Belgium; CNRS-UMR 5548, Faculté de Sciences Gabriel (F.B.-A.), Université de Bourgogne, Dijon, France; and the Unité dEndocrinologie et Métabolisme (J.-C.J.), University of Louvain, Brussels, Belgium.
Correspondence to Jan B. Parys, Laboratorium voor Fysiologie, KU Leuven, Campus Gasthuisberg O/N, Herestraat 49, B-3000 Leuven, Belgium. E-mail jan.parys{at}med.kuleuven.ac.be
AbstractAltered Ca2+ handling is observed in different cells in essential hypertension. We investigated the expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and inositol 1,4,5-trisphosphate receptor (IP3R) isoforms in platelets and aortic endothelial cells (EC) isolated from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats by ratio reverse-transcriptasepolymerase chain reaction (RT-PCR) analysis and Western blotting. SERCA2b and SERCA3 were assessed at mRNA (EC and platelets) and at protein level (platelets). IP3R1, IP3R2, and IP3R3 mRNAs were demonstrated in both cell types, but only IP3R1 and IP3R2 proteins were detected in platelets. Compared with WKY, SHR EC and platelets showed higher SERCA3 and IP3R2 expression and lower IP3R1 expression. We then investigated the effect of lisinopril (20 mg · kg-1 · d-1; 10-week treatment of 4-week-old rats or 2-week treatment of adult rats) and captopril (100 mg · kg-1 · d-1; 2-week treatment of adult rats). Consequently, expression patterns of SERCAs and IP3Rs were significantly modified. Except for SERCAs mRNA in platelets, all differences between SHR and WKY disappeared. However, SERCA3 remained the predominant isoform. Both EC and platelets demonstrated a high equal expression of IP3R2 mRNA. IP3R1 was the predominant platelet protein isoform, as it was in untreated WKY. mRNA was also isolated from pancreatic islets of WKY and SHR, but no effect of either rat strain or of lisinopril treatment was observed on the expression of the studied genes. We hypothesize that the identical expression pattern of SERCAs and IP3Rs after treatment with ACE inhibitors represents a different nonhypertensive configuration, which, through changes in intracellular Ca2+ handling, improves endothelial and platelet dysfunction in SHR but has no effect in WKY.
Key Words: inositol 1,4,5-trisphosphate receptor sarco(endo)plasmic reticulum Ca2+-ATPase receptors, angiotensin angiotensin-converting enzyme inhibitors platelets endothelium hypertension, experimental
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