Alterations in cytosolic calcium-binding proteins that increase felodipine fluorescence in spontaneously hypertensive rats.
OBJECTIVE
To clarify the role of calcium-binding proteins (CaBP) in hypertension.


METHODS
CaBP from several organs of spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats were purified and their characteristics compared between the two strains. The CaBP were purified by applying the soluble cytosolic fractions from mesenteric vessels, heart, kidney and brain of 4- and 10-week-old SHR and WKY rats to a phenyl-Sepharose column. Felodipine binding to the purified CaBP was then measured.


RESULTS
The fluorescence intensity of felodipine increased in a calcium-dependent manner when it bound to CaBP. The pK 0.5 Ca2+ values derived from the calcium ion-felodipine fluorescence curves for each CaBP preparation from organs of the two strains were similar, indicating that the calcium sensitivities of the CaBP to the felodipine binding process are similar in SHR and WKY rats. In 10-week-old SHR the mean levels of felodipine-bound CaBP in heart, brain and kidney were significantly altered compared with those in WKY rats. No such alterations were observed in heart, kidney and brain from 4-week-old SHR and WKY rats. Conversely, the mean levels of felodipine-bound CaBP in mesenteric vessels from 4- and 10-week-old SHR were reduced significantly compared with those of age-matched WKY rats.


CONCLUSIONS
These results suggest that the levels of cytosolic felodipine-bound CaBP from heart, kidney and brain are altered in response to elevated blood pressure, and that reduced levels of felodipine-bound CaBP in the mesenteric vessels of SHR might be a primary characteristic of this rat strain.
Hojo
Y
Y
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Ebata
H
H
Kawasaki
K
K
Tsuruya
Y
Y
Ikeda
U
U
Nishinaga
M
M
Natsume
T
T
Shimada
K
K
D000818:Animals; D001921:Brain / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D015736:Felodipine / Q000378:metabolism*; D005453:Fluorescence; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D008642:Mesenteric Veins / Q000378:metabolism; D008970:Molecular Weight; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity
D002135:Calcium-Binding Proteins; D015736:Felodipine