Effect of Inhibition of Sarcoplasmic Ca²⁺-ATPase on Vasoconstriotion and Cytosolic Ca²⁺in Aortic Smooth Muscle from Spontaneously Hypertensive and Normotensive Rats

Abstract

To evaluate the influence of the sarcoplasmic Ca(2+)-ATPase, isometric vasoconstrictions of aortic strips from spontaneously hypertensive rats from the Münster strain (SHR) and normotensive Wistar-Kyoto rats (WKY) were measured after inhibition of Ca(2+)-ATPase by thapsigargin. Inhibition of Ca(2+)-ATPase by thapsigargin caused a biphasic contractile response 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, respectively; mean +/- SE). The second peak of the contractile response was abolished in the absence of external calcium or by inhibition of transplasmamembrane calcium influx by nifedipine, indicating that the second peak occurs as a consequence of calcium influx from the extracellular space. The initial peak of the contractile response after thapsigargin administration was abolished in the presence of an intracellular calcium antagonist, 8-(diethylamino-)-octyl-3,4,5-trimethoxybenzoate (TMB-8), indicating that the initial response was due to calcium release from intracellular stores. Measurements using the fluorescent dye fura2 showed that thapsigargin increased the cytosolic free calcium concentration ([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 the two strains. The inhibition of Ca(2+)-ATPase increases [Ca2+]i and causes vasoconstriction. The vasoconstriction produced by thapsigargin is not significantly different between SHR and WKY.

Increased store-operated and 1-oleoyl-2-acetyl-sn-glycerol-induced calcium influx in monocytes is mediated by transient receptor potential canonical channels in human essential hypertension

“…This finding is in line with several previous reports showing an increased store-operated calcium influx in primary hypertension [45][46][47].…”

Trans- andcis-resveratrol increase cytoplasmic calcium levels in A7r5 vascular smooth muscle cells

“…A similar result was obtained for THAPS, in good agreement with the results of Tepel et al [25] (see above).…”

“…[23], has been shown to transiently block THAPS-induced rise in [Ca 2+ ] i for about 20 min [24] and to abolish the initial peak of the contractile response induced by THAPS in rat aortic strips [25]. In the same work, Tepel et al [25] have also shown that the second phase of the response to THAPS was not inhibited by TMB-8, but it was completely abolished in the absence of extracellular Ca 2+ . According to this, in our experiments in the absence of extracellular Ca 2+ , TMB-8 completely abolished the increase in [Ca 2+ ] i induced by THAPS.…”

“…Finally, after partial depletion of intracellular Ca 2+ stores by RESV, the response to a subsequent application of an agonist acting through a phospholipase C and inositol 1,4,5-triphosphate-mediated mechanism, could be significantly reduced. [23], has been shown to transiently block THAPS-induced rise in [Ca 2+ ] i for about 20 min [24] and to abolish the initial peak of the contractile response induced by THAPS in rat aortic strips [25]. In the same work, Tepel et al [25] have also shown that the second phase of the response to THAPS was not inhibited by TMB-8, but it was completely abolished in the absence of extracellular Ca 2+ .…”

Cyclic stretch decreases TRPC4 protein and capacitative calcium entry in rat vascular smooth muscle cells

“…Myogenic tone develops when Ca 2+ entry through these stretch-activated channels causes membrane depolarization, activation of voltage-gated channels, and smooth muscle cell contraction (Davis et al, 1992b). Increased vascular tone can also result from store-operated Ca 2+ entry, also termed capacitative Ca 2+ entry (CCE), which occurs after SR depletion and activation of plasma membrane store-operated channels (Tepel et al, 1994;Low et al, 1996). Elevated intraluminal pressure reduces CCE in skeletal muscle arterioles, but in human myometrial smooth muscle cells, static stretch has the opposite effect of increasing CCE (Potocnik and Hill, 2001;Dalrymple et al, 2007).…”