EFFECT OF INHIBITION OF SARCOPLASMIC CA2-ATPASE ON VASOCONSTRICTION AND CYTOSOLIC CA2+ IN AORTIC SMOOTH-MUSCLE FROM SPONTANEOUSLY HYPERTENSIVE AND NORMOTENSIVE RATS()
M. Tepel et al., EFFECT OF INHIBITION OF SARCOPLASMIC CA2-ATPASE ON VASOCONSTRICTION AND CYTOSOLIC CA2+ IN AORTIC SMOOTH-MUSCLE FROM SPONTANEOUSLY HYPERTENSIVE AND NORMOTENSIVE RATS(), Clinical and experimental hypertension, 16(4), 1994, pp. 493-506
Citations number
29
Categorie Soggetti
Pharmacology & Pharmacy","Cardiac & Cardiovascular System
To evaluate the influence of the sarcoplasmic Ca2+-ATPase, isometric v
asoconstrictions of aortic strips from spontaneously hypertensive rats
from the Munster strain (SHR) and normotensive Wistar-Kyoto rats (WKY
) were measured after inhibition of Ca2+-ATPase by thapsigargin. Inhib
ition of Ca2+-ATPase by thapsigargin caused a biphasic contractile res
ponse of the aorta in both SHR and WKY (maximum increase of tension: 1
.7 +/- 0.3 x 10(-3) Newton and 2.1 +/- 0.3 x 10(-3) Newton, respective
ly; mean +/- SE). The second peak of the contractile response was abol
ished in the absence of external calcium or by inhibition of transplas
mamembrane calcium influx by nifedipine, indicating that the second pe
ak occurs as a consequence of calcium influx from the extracellular sp
ace. The initial peak of the contractile response after thapsigargin a
dministration was abolished in the presence of an intracellular calciu
m antagonist, 8-(diethylamino-)-octyl-3,4,5-trimethoxy benzoate (TMB-8
), indicating that the initial response was due to calcium release fro
m intracellular stores. Measurements using the fluorescent dye fura2 s
howed that thapsigargin increased the cytosolic free calcium concentra
tion ([Ca2+](i)) in SHR by 72.6 +/- 7.3 nmol/l (n=34) and in WKY by 53
.3 +/- 6.6 nmol/l (n=39), showing no significant differences between t
he two The inhibition of Ca2+-ATPase increases [Ca2+](i) and causes va
soconstriction. The vasoconstriction produced by thapsigargin is not s
ignificantly different between SHR and WKY.