|Budget Amount *help
¥8,800,000 (Direct Cost : ¥8,800,000)
Fiscal Year 2000 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1999 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1998 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1997 : ¥6,900,000 (Direct Cost : ¥6,900,000)
Isoflurane and sevoflurane, volatile anesthetics now commonly used in Japan, at clinically relevant concentrations significantly influence contractile response to norepinephrine (NE), a sympathetic neurotransmitter, in isolated mesenteric resistance arteries. The action of these anesthetics on contractile response to NE consists of endothelium-dependent vasoconstricting and endothelium-independent vasodilating components. In the presence of endothelium, the former predominates over the latter, enhancing the NE response, while in the absence of endothelium, only the latter emerges, inhibiting the NE response. Nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase products, lipoxygenase products, endothelin-1, angiotensin II, or serotonin are not involved in their vasoconstricting action. Isoflurane may stimulate release of superoxide anions from endothelial cells, thereby enhancing the NE response.
Sevoflurane appears to inhibit vascular smooth muscle contraction by b
oth reducing the intracellular Ca^<2+> concentration ([Ca^<2+>]i) and inhibiting myofilament Ca^<2+> sensitivity. The [Ca^<2+>]i-reducing effect is mainly caused by inhibition of voltage-gated Ca^<2+> influx, while its inhibitory action on myofilament Ca^<2+> sensitivity seems to require an intact cell membrane. Four volatile anesthetics halothane, isolfurane, enflurane and sevoflurane have differential effects on various functions of intracellular calcium stores of mesenteric resistance arterial smooth muscle cells such as the amount of stored Ca^<2+>, Ca^<2+> uptake, or Ca^<2+>-releasing mechanisms. These anesthetics may significantly influence vascular tone or reactivity of mesenteric resistance arteries through their various effects on the intracellular calcium stores.
Mechanisms of the action of ketamine, an intravenous anesthetic, on isolated mesenteric resistance arteries were also investigated and reported. The effects of various halogenated volatile anesthetics on isolated hepatic and renal arteries are currently under investigation.