The Effect of Halothane and Enflurane on the Aorta Contracted with Phenylephrine in Rabbits / 대한마취과학회지

BACKGROUND: Inhalation anesthetics have been known as vasodilators, but there are several reports that halothane and enflurane have different effects on vascular smooth muscles. Vasodilatation and vasoconstriction were observed in different vessels in the same animal. We tried to observe the effect of halothane and enflurane on the contraction of the aorta in rabbits. METHODS: Isolated tracheal preparations of rabbits were used. Halothane (1.4%) and enflurane (1.4%, 2.8% and 5%) were administered after contractions induced by phenylephrine (10(-7) M), and verapamil (10(-7), 10(-6), 10(-5), 10(-4), and 10(-3) M) was administered. In the verapamil pretreated group, after a phenylephrine (10(-7) M) induced contraction, verapamil (10(-7) M) and enflurane (2.8% and 5%) were administered. The percentile contraction to the contraction induced by phenylephrine was evaluated. RESULTS: The potentiation of the contration by phenypephrine was observed by halothane and enflurane administration and these potentiations disappeared with the adminstration of verapamil. With prior administration of verapamil, there was no potentiation of the contraction by enflurane. CONCLUSIONS: Halothane and enflurane potentiates the contraction induced by phenylephrine in rabbit aortas. In addition, the influx of extracellular calcium seems to play a role in this potentiation of the contraction.

Effects of Mivacurium in the Strips of Rat Thoracic Aortic Rings / 대한마취과학회지

BACKGROUND: The hypotensive effects of muscle relaxants has traditionally been associated with a ganglion block and histamine release. However, it was exhibited that the ability of certain analogues of the steroidal muscle relaxant directly caused relaxation of isolated vascular smooth muscles. The ability of mivacurium to elicit a direct relaxant effect on vascular smooth muscle has been studied using isolated rat thoracic aortic rings contracted with phenylephrine (PE). METHODS: Each ring of the thoracic aorta was suspended on wire supports in a 20 ml tissue bath under 2 gm of resting tension. All tissues were bathed in a Tris Tyrode solution at 37oC and 100% oxygen was supplied. RESULTS: Mivacurium 3 X 10 5 M and 10 3 M inhibited PE induced contractions of the aortic rings significantly (P < 0.05) and shifted the cumulative concentration-effect curves of PE to the right. The maximum contractile response from 81.9% to 55.0% (with PE 10 6 M) was the same as that seen with mivacurium 10 3 M pretreatment. Relaxation of aortic ring with mivacurium 10 3 M was not reversed with L-NAME pretreatment. Methylene blue reversed the relaxation of the aortic rings with mivacurium 10 3 M and shifted the cumulative concentration-effect curve of PE to the left. Indomethacine enhanced the relaxation of the aortic rings with mivacurium 10 3 M and shifted this curve to the right. Mivacurium 10 3 M inhibited the influx of extracellular Ca2+. CONCLUSIONS: The results suggest that the relaxation effects of mivacurium is related with the endothelium and at least, in part, cyclooxygenase inhibition and guanylate cyclase activation are related with this relaxation effect. Also, mivacurium inhibited extracelluar calcium influx.

Vasodilatory Action of Propofol and the Effect of Propofol on the Contractile Response of Endotoxin Exposured Vessles in the Aortic Arteries of Rats / 대한마취과학회지

BACKGROUND: The relationship between the NO and its vasodilatory effect of propofol has been a somewhat controversial matter. And, the effects of propofol has not been evaluated in septic condition whether it is solely due to its increased iNOS activity. METHODS: First experiment is to study that the vasodilatory effect of propofol could be caused by NO. Isolated aortic rings with or without endothelium were contracted phenylephrine (10(-9)-10(-5)M) cumulatevely after porpofol (10(-5)M) administration. The effects of L-NAME (3 x 10(-4)M) and methylene blue (10(-5)M) on contractile responses for phenylephrine were evaluated. Second experiment is to study the effect of propofol on septic vesseles. the no LPS (lypopolysaccaride) and LPS treated rings with or without endothelium were contracted phenylephrine (10(-9)-10(-5)M) cumulatevely after porpofol (10(-5)M) administration. The development of sepsis was confirmed by iNOS expression using RT-PCR. RESULTS: All the aortic rings showed decreased response on phenylephrine contractile response with propofol administration. These responses were significantly less in denuded ones than in ones with intact endothelium. The endothelium dependent relaxation of propofol was inhibited by pretreatment with L-NAME and methylene blue in rat aortic rings having intact endothelium. All the aortic rings incubated with LPS showed decreased phenylephrine contractile response. The addition of propofol produced significantly more decrease in contractile response in LPS incubated rings in a greater than additive effect. The LPS induced hyporesponsiveness to phenylephrine was reversed by addition of cycloheximide. However, with the addition of propofol to LPS treated rings, complete reversal of this hyporesponsiveness to phenylephrine, failed to occur by addition of cycloheximide. CONCLUSIONS: 1) The vasodilatory effect of propofol seems to be mediatede by EDRF/NO, 2) The vasodilatory effect of propofol is increased in septic vesseles. Moreover, the inability of nitric oxide synthase inhibitior to reverse this response completely suggest that increased induction of iNOS may not be a sole responsible factor for this finding.

The Vasodilation of Protamine and the Influence of Heparin on its Actions in the Isolated Aortic Arteries of Rats / 대한마취과학회지

BACKGROUND: When used to reverse the anticoagulant effect of heparin, protamine administration after cardiovascular bypass often can lead to systemic hypotension. During the reversal of heparin-induced anticoagulation, the effects of protamine on both a heparin-protamine complex and free protamine on the cardiovascular system should be considered. METHOD: To determine whether the hypotensive effect of heparin-protamine and/or protamine could be caused by endothelium-dependent and-independent component, we studied rings of the arotic arteries in rats suspended in organ chambers containing Tris Tyrode solution at 37oC and 100% O2. Arterial rings with or without endothelium were contracted with 40 mM KCl or 3 +/- 10-6M phenylephrine and then exposed to increasing concentrations of protamine (final organ bath concentration, 40~400 g/ml) both in the absence and presence of heparin (200 U/ml). RESULTS: Protamine induced concentration-dependent relaxation in arterial rings with endothelium, which were significantly greater than in rings without endothelium. The endothelium-dependent relaxation induced by protamine was inhibited by NG-monomethyl-L-arginine (L-NMMA) (10-5M) pretreatment, but was not inhibited by indomethacin (3x10-6M) pretreatment on rings with endothelium. Furthermore, the contractile inhibition was enhanced by superoxide dismutase (100 U/ml). Also, such vasodilating actions were not influenced in the presence of heparin (200 U/ml). In endothelium-denuded strips, protamine (400ug/ml) inhibited Ca++ induced contraction, which was evoked in Ca++-free solution containing 40 mM K+, and also inhibited the norepinephrine (NE)-induced contraction. Protamine inhibited on the NE-induced contraction, but not the caffein-induced contration in Ca++ free, 2 mM EGTA solution. Also, such inhibition of contracions were not inluenced in the presence of heparin (40 U/ml). CONCLUSION: This study demonstrates that protamine (in the presence or absence of heparin) acts on endothelial cell receptors to stimulate the production of nitric oxide and inhibits both Ca++-influx and the NE-induced Ca++ release from intracellular stores.