Potentiation by endothelin-1 of Ca2+ sensitivity of contractile elements depends on Ca2+ influx through L-type Ca2+ channels in the canine cerebral artery

Tanaka, Yoshio; Ishiro, Hiromi; Nakazawa, Tomoo; Saito, Masanori; Ishii, Kunio; Nakayama, Koichi

doi:10.1016/0306-3623(94)00258-o

Cited by 9 publications

(10 citation statements)

References 39 publications

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“…At the same time, this constriction required Ca 2ϩ influx through voltage-dependent Ca 2ϩ channels. The Ca 2ϩ requirement for endothelin-induced Ca 2ϩ sensitization has also been demonstrated in canine basilar artery (44). In the present study, histamine-induced contraction was strongly attenuated by nifedipine; therefore, influx of Ca 2ϩ through voltage-dependent Ca 2ϩ channels opened by depolarization might be essential not only for stimulation of contraction, but also for the Ca 2ϩ sensitization of the contractile process.…”

Section: Discussionsupporting

confidence: 71%

“…An additional or alternative mechanism contributing to histamine-induced contraction in rabbit MCA might be an increase in the Ca 2ϩ sensitivity of the contractile process. Such a mechanism has been demonstrated in some smooth muscle stimulated with norepinephrine, endothelin, or histamine (11,19,24,33,44). There is evidence that activation of protein kinase C might be responsible for enhancement of Ca 2ϩ sensitivity (19).…”

Section: Discussionmentioning

confidence: 90%

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Histamine-induced depolarization: ionic mechanisms and role in sustained contraction of rabbit cerebral arteries

Gokina

Bevan

2000

American Journal of Physiology-Heart and Circulatory Physiology

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The role of membrane depolarization in the histamine-induced contraction of the rabbit middle cerebral artery was examined by simultaneous measurements of membrane potential and isometric force. Histamine (1-100 microM) induced a concentration-dependent sustained contraction associated with sustained depolarization. Action potentials were observed during depolarization caused by histamine but not by high-K(+) solution. K(+)-induced contraction was much smaller than sustained contraction associated with the same depolarization caused by histamine. Nifedipine attenuates histamine-induced sustained contraction by 80%, with no effect on depolarization. Inhibition of nonselective cation channels with Co(2+) (100-200 microM) reversed the histamine-induced depolarization and relaxed the arteries but induced only a minor change in K(+)-induced contraction. In the presence of Co(2+) and in low-Na(+) solution, histamine-evoked depolarization and contraction were transient. We conclude that nonselective cation channels contribute to histamine-induced sustained depolarization, which stimulates Ca(2+) influx through voltage-dependent Ca(2+) channels participating in contraction. The histamine-induced depolarization, although an important and necessary mechanism, cannot fully account for sustained contraction, which may be due in part to augmentation of currents through voltage-dependent Ca(2+) channels and Ca(2+) sensitization of the contractile process.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 90%

Histamine-induced depolarization: ionic mechanisms and role in sustained contraction of rabbit cerebral arteries

Gokina

Bevan

2000

American Journal of Physiology-Heart and Circulatory Physiology

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“…The cellular mechanisms for smooth muscle sensitization are likely to involve both an ET-1-dependent increase in Ca 2ϩ influx and Ca 2ϩ sensitivity of contractile elements via a protein kinase C-dependent mechanism. 20,21 Contractions induced by exogenous ET-1 were also shifted to the right in the presence of the selective ET A receptor antagonist without change in maximal response and were almost completely blocked by bosentan, a nonselective ET A/B receptor antagonist. This suggests that ET B receptors are responsible for ET-1-induced contraction in rat cerebral arteries.…”

Section: Vascular Reactivity To ␣ 1 -Adrenergic Agonist and Etmentioning

confidence: 99%

Endothelin-1 Regulates Tone of Isolated Small Arteries in the Rat

1998

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Abstract-Chronic elevation of plasma endothelin-1 (ET-1) levels has been reported in several pathological conditions. To investigate the consequences of increased circulating ET-1 on vascular responsiveness, Sprague-Dawley rats (nϭ16) were chronically instrumented with a minipump delivering ET-1 at a constant dose for 7 days. Plasma ET-1 levels were more than doubled in treated (0.98Ϯ0.09 pmol/L; PϽ.05) versus untreated sham-operated rats (0.43Ϯ0.04 pmol/L), whereas systolic arterial blood pressure increased (139Ϯ5 versus 128Ϯ4 mm Hg in untreated rats; PϽ.05). After rats were killed, segments of middle cerebral (MCA) and mesenteric (MES) arteries were mounted on an isometric myograph. ET-induced contraction was shifted to the right in ET-1-treated animals and not modified by BQ123 (an ET A receptor antagonist); bosentan (ET A/B receptor antagonist) prevented ET-1-induced contraction in both groups. After inhibition of nitric oxide synthase with N -nitro-L-arginine (L-NNA), both phenylephrine and oxymetazoline (an ␣ 2 -adrenoceptor agonist) induced MCA contraction. The sensitivity to phenylephrine was decreased in ET-1-treated compared with control rats (PϽ.05). Sensitivity to phenylephrine-induced contraction was decreased by BQ123 in control rats only. In contrast, L-NNA revealed greater oxymetazoline-induced contractions in treated compared with control MCA rings (PϽ.05); this potentiation was blunted by bosentan but unaffected by BQ123. Removal of the endothelium revealed a direct constrictor effect of oxymetazoline that was insensitive to L-NNA alone or combined with bosentan; however, oxymetazoline induced significantly lower constriction in treated rat MCA segments. Responses to oxymetazoline were also blunted in treated compared with untreated denuded MES arteries. In conclusion, chronic elevated plasmatic ET-1 decreases smooth muscle cell sensitivity to contractile agonists both in MCA and MES rings. In cerebral vessels, endothelial ␣ 2 -adrenoceptor-dependent stimulation induced greater contractile responses in treated rats which were sensitive to bosentan, suggesting that oxymetazoline stimulates ET-1 release from the endothelium. This may represent a compensatory mechanism for the loss of smooth muscle sensitivity. (Hypertension. 1998;31:1035-1041.)

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“…Cerebral arteries in a rodent model of SAH have an enhanced responsiveness to ET (Alafaci et al, 1990). The endothelial peptide ET augments the responses to a number of vasoconstrictors by increasing the Ca 2+ sensitivity of contractile proteins, for example, in coronary and cerebral arteries (Tanaka et al, 1995;Obara et al, 1999). Interestingly, enhanced vascular tone occurs in the absence of greater MLC phosphorylation, and the resultant enhanced vascular response is only partially inhibited by Ca 2+ channel inhibitors but is completely sensitive to calphostin, H-7, and staurosporine inhibitors of PKC (Obara et al, 1999;Nakayama et al, 1991).…”

Section: Cerebral Artery Tonementioning

confidence: 99%

Protein Kinase C and Cerebral Vasospasm

Laher

Zhang

2001

J Cereb Blood Flow Metab

127

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Twenty-five years after the discovery of protein kinase C (PKC), the physiologic function of PKC, and especially its role in pathologic conditions, remains a subject of great interest with 30,000 studies published on these aspects. In the cerebral circulation, PKC plays a role in the regulation of myogenic tone by sensitization of myofilaments to calcium. Protein kinase C phosphorylates various ion channels including augmenting voltage-dependent Ca2+ channels and inhibiting K+ channels, which both lead to vessel contraction. These actions of PKC amplify vascular reactivity to different agonists and may be critical in the regulation of cerebral artery tone during vasospasm. Evidence accumulated during at least the last decade suggest that activation of PKC in cerebral vasospasm results in a delayed but prolonged contraction of major arteries after subarachnoid hemorrhage. Most of the experimental results in vitro or in animal models support the view that PKC is involved in cerebral vasospasm. Implication of PKC in cerebral vasospasm helps explain increased arterial narrowing at the signal transduction level and alters current perceptions that the pathophysiology is caused by a combination of multiple receptor activation, hemoglobin toxicity, and damaged neurogenic control. Activation of protein kinase C also interacts with other signaling pathways such as myosin light chain kinase, nitric oxide, intracellular Ca2+, protein tyrosine kinase, and its substrates such as mitogen-activated protein kinase. Even though identifying PKC revolutionized the understanding of cerebral vasospasm, clinical advances are hampered by the lack of clinical trials using selective PKC inhibitors.

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Potentiation by endothelin-1 of Ca2+ sensitivity of contractile elements depends on Ca2+ influx through L-type Ca2+ channels in the canine cerebral artery

Cited by 9 publications

References 39 publications

Histamine-induced depolarization: ionic mechanisms and role in sustained contraction of rabbit cerebral arteries

Histamine-induced depolarization: ionic mechanisms and role in sustained contraction of rabbit cerebral arteries

Endothelin-1 Regulates Tone of Isolated Small Arteries in the Rat

Protein Kinase C and Cerebral Vasospasm

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