Effects of Thiopental Sodium, Midazolam, Propofol and Ketamine on Endothelial Nitric Oxide in Rat Thoracic Aortic Rings / 대한마취과학회지

BACKGROUND: Compared to inhalation and local anesthetics, little is known about the mechanisms of vascular effects of intravenous anesthetics. So we studied the effects of thiopental sodium, midazolam, propofol and ketamine on the endothelial nitric oxide-cGMP pathway and also on the membrane cyclooxygenase pathway. METHODS: After isolating ring strips of rat thoracic aorta, we measured the relaxation ED50 values of the four intravenous anesthetics from the maximally contracted using phenylephrine 10(-5)M. Then using L-NAME and methylene blue, we studied the effects of the drugs upon the NO-cGMP system. In addition, another pathway of vasodilation through membrane prostaglandin metabolism was examined using the membrane cyclooxygenase inhibitor, indomethacine. RESULTS: The following results were obtained. 1. Thiopental sodium (10(-5)M) did not have any effect on the PE induced contractions of aortic rings but midazolam (10(-6)M), propofol (10(-4)M) and ketamine (10(-3)M) significantly (P < 0.05) inhibited the PE induced contractions of aortic rings. 2. Midazolam 10(-6)M and propofol 10(-4)M induced relaxation of aortic rings were recovered with L-NAME pretreatment but ketamine induced relaxation was not recovered with L-NAME. 3. Midazolam 10(-6)M induced relaxation was not recovered with methylene blue pretreatment, but propofol 10(-4)M induced relaxation was recovered with methylene blue. 4. Indomethacine pretreatment induced further relaxation of midazolam or propofol induced relaxation of aortic rings. CONCLUSIONS: Midazolam, propofol and ketamine, but not thiopental sodium, relax rat thoracic aortic rings, and these relaxation effects of midazolam and propofol are endothelium dependent. Cyclooxygenase inhibition is related at least in part to midazolam or propofol induced relaxation, and guanylate cyclase to propofol induced relaxation.

Acute cyclosporin A-treatment impairs the cytosolic guanylate cyclase-mediated vasodilatation in rat thoracic aorta

Cyclosporin A (CsA), a widely used immunosuppressant, is well known to cause nephrotoxicity and hypertension as major side effects. The present study was aimed at investigating the effects of CsA-pretreatment on the activities of cytosolic guanylate cyclase (cGC) in relation to the alteration of relaxant responses in the rat thoracic aorta. CsA (10 micrometer)-preincubation for 90 min significantly attenuated the vasodilatation induced by sodium nitroprusside (SNP), a cytosolic guanylate cyclase activator, shifting the dose-response curve to the right. The increase in cGMP contents induced by SNP was markedly attenuated by CsA. SNP (1 micrometer apprx 1 mM) increased the cGC activity dose-dependently, and the increase was completely abolished by CsA. CsA attenuated the SNP-induced cGC activation dose-dependently. The abolishing effect of CsA-pretreatment on the SNP-induced cGC activation was not affected by washing the preparation, suggesting that the inhibition is irreversible. When CsA was added simultaneously with SNP, cGC activation was not attenuated. 1-(5-isoquinolinylsulfonyl)-2-methyl piperazine (H-7), a protein kinase C (PKC) inhibitor, decreased SNP-induced cGC activation and blocked the CsA-attenuation of cGC activation. These results suggest that CsA directly inhibits cGC participating in the CsA-induced impairment of vasodilatation, and that PKC is involved in the inhibitory action of CsA on cGC.

Effect of K+ channel Blocker on Vasodilation by Halothane / 대한마취과학회지

Halothane is a popular inhalation anesthetics in practice, which has been reported to cause a vasodilation through a direct depressant action on vascular smooth muscle, or by an indirect attenuation of vasoconstrictor activity. The membrane potential of the vascular smooth muscle cell is mainly regulated by the flow of Ca2+ and K+ ions through specialized channels. The purpose of this study was to determine whether blockade of the K+ channel alter the response to halothane vasodilating action. This study was done with rat thoracic aorta in tissue bath. Isometric tension of the ring (3~4 mm in length) was recorded. In halothane alone group (n=15), after precontraction with norepinephrine (10(-7) M), ring was exposed with halothane 0.7%, 1.5%, 2.1% concentration for 15 minutes, sequentially. The procedure of calcium activated K+ channel blocker pretreated group (n=12) was same manner as halothane alone group after tetraethylammonium (TEA 20 mM) pretreatment. The result of this study was shown to followings; 1) Vasodilation correlate with halothane concentration (p<0.05). 2) Vasodilation in tetraethylammonium (TEA) pretreated group also augmented 'significantly (p<0.05). 3) Especially, in the halothane 1.5%, 2.1%, the presence of TEA significantly potentiate vasodilating effect: halothane alone group, -35%, -53%: TEA group, -47%, -71%(p<0.05). These result demonstrate that: 1) halothane induce relaxation of rat aorta. 2) K+ charinel blokade potentiate the vasodilating effect of halothane.