Enhanced spontaneous calcium efflux and decrease of calcium-dependent calcium release from the isolated perfused heart of spontaneously hypertensive rats.
OBJECTIVE
The aim of this study was to clarify the further details of calcium handling in hypertension.


METHODS
By preserving the physiological environment of cell membrane, whole hearts were used for comparison of calcium flux between spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats.


METHODS
Hearts from SHR and WKY rats were perfused with Krebs-Henseleit solution under constant flow and the effluent collected.


RESULTS
After labelling of the heart with 45Ca2+ (100 mumol/l), 45Ca2+ binding was found to be saturated, and washing with calcium-free perfusion solution showed two exponential curves for calcium dissociation, indicating a fast (alpha-) and slow (beta-) phase. The half-lives of the beta-phase for both 4- and 8-week-old SHR were significantly shorter than those for age-matched WKY. Also in this phase, infusion of non-radioactive Ca2+ caused a transient dose-dependent release of 45Ca2+. A significant reduction in the amount of 45Ca2+ release induced by 2 mmol/l Ca2+ was observed in both 4- and 8-week-old SHR compared with age-matched WKY rats. Infusion of lanthanum, caffeine, ionomycin (calcium ionophore) and treatment of the hearts with ethyleneglycol-bis-(beta-aminoethylether)-N,N,N,',N'-tetraac etic acid did not alter 45Ca2+ release by non-radioactive Ca2+. From these observations, 45Ca2+ is presumably released from the intracellular calcium pool, and not from extracellular binding sites or sarcoplasmic reticulum.


CONCLUSIONS
These findings suggest that an abnormal calcium-handling defect (enhanced calcium efflux and reduction of membrane-bound Ca2+) exists under physiological conditions before and after the onset of hypertension, and that this may be a primary characteristic of SHR.
Hojo
Y
Y
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Ebata
H
H
Ikeda
U
U
Tsuruya
Y
Y
Natsume
T
T
Shimada
K
K
D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D004533:Egtazic Acid / Q000494:pharmacology; D006207:Half-Life; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011921:Rats, Inbred WKY
D002132:Calcium Radioisotopes; D002110:Caffeine; D004533:Egtazic Acid; D015759:Ionomycin; D007811:Lanthanum; D002118:Calcium