No abstract available.
Aorta* ; Endothelium-Dependent Relaxing Factors*

PURPOSE: This study was done to determine whether maturatin alters endothelium- dependent responses in pulmonary arteries. METHODS: Vascular rings of pulmonary arteries, with and without endothelium, taken from rabbits of 3 and 30 days of age were suspended in organ chambers filled with Krebs-Henseleit solution, bubbled with 95% O2-5% CO2 and maintained at 37degrees C. Immediately after mounting, the rings were stretched progressively until a maximal response to KCl was achieved. The rings were incubated with indomethacin and allowed to equilibrate before contraction and relaxation study. RESULTS: When the endothelium was intact in arterial rings from 3-day-old rabbits, acetylcholine (ACH) (10-6 M) relaxed preconstricted rings with histamine (5x10-6 M) (98.1 4.7% relaxation, mean SD). In rings without endothelium, KCl (10-2 to 9x10-2 M) and histamine (5x10-8 to 10-5 M) caused concentration-dependent contractions. When normalized to maximal contractions achieved to each agonist, the concentration-effect curves to KCl and histamine in rings without endothelium were similar to both ages. Rings with endothelium showed a progressive shift to the right of the concentration- effect curve to histamine. Relaxation to sodium nitroprusside were unaffected by age. In preconstricted ring, ACH (10-8 to 5x10-6 M) caused relaxations in rings with endothelium which were greater at 30-day compared to 3-day-old rabbits. CONCLUSION: These study demonstrates that endothelium-dependent relaxation increase with age, possibly due to changes in the release and/or effect of endothelium-derived relaxing factor (EDRF or nitric oxide) from pulmonary arteries during the neonatal period.
Acetylcholine ; Endothelium ; Endothelium-Dependent Relaxing Factors ; Histamine ; Humans ; Indomethacin ; Infant, Newborn* ; Nitroprusside ; Pulmonary Artery* ; Rabbits ; Relaxation*

PURPOSE: There have been conflicting reports on vascular response to Panax ginseng. The conflicting reports may be due to difference of ingredient of Panax ginseng. The aim of the present study was to investigate the effect of saponin, the main ingredient of Panax ginseng, on the vascular contractility. METHODS: The rabbit aortic rings were cut and mounted on the force transducer to record an isometric tension on polygraph. To elucidate the mechanism of saponin effect on vascular smooth muscle, the contractility of the vascular smooth muscle were measured under varying experimental condition. RESULTS: 1) When the aortic rings were precontracted with norepinephrine, saponin caused biphasic(initial relaxation-sustained contraction) dose-response in the endothelium dependent manner. But saponin had no effect on the resting tension. 2) When EDRF inhibitors such as methylene blue(10(-5)M), hemoglobin(10(-5)M), N-omega-nitro-L-arginine(100microM) were added to precontracted ring with norepinephrine, the initial relaxation caused by 2mg% saponin was inhibited. 3) When Ca(2+)-channel blocker, nifedipine(5x10(-7)M), was added to precontracted rings with norepinephrine, the sustsined contraction by saponin was inhibited. 4) When hemoglobin(10(-5)M) was added to precontracted rings with norepinephrine, the contractility by norepinephrine was increased and this effect was further augmented by 2mg% saponin. CONCLUSIONS: From the above results, it may be concluded that saponin stimulated the release of both an endothelium-dependent relaxing factor and endothelium-dependent contracting factor.
Endothelium ; Endothelium-Dependent Relaxing Factors ; Muscle, Smooth, Vascular ; Norepinephrine ; Panax ; Relaxation ; Saponins* ; Transducers

BACKGROUND: It is generally accepted that propofol does not inhibit hypoxic pulmonary vasoconstriction (HPV). However, because the previous studies for the effects of propofol on HPV were established in vivo, the effects of physiologic variables could not be ruled out. Therefore, we investigated the effects of various concentrations of propofol on HPV at isolated rat lungs and the relationship of these effects of propofol on HPV and endothelium-derived relaxing factor (EDRF) and an ATP-dependent K+ channel which were candidates as the mechanism of HPV. METHODS: In 30 isolated rat lungs, after three hypoxic challenges for 5 minutes, we administered saline in the control group, N(G)-nitro-L-arginine methyl ester (L-NAME) in the L group and glibenclamide in the G group followed by three hypoxic challenges for 5 minutes. In addition, we studied the effects of various concentrations of propofol on HPV in the three groups. RESULTS: L-NAME and glibenclamide did not alter baseline pulmonary arterial pressure but L-NAME significantly enhanced HPV. Clinical concentrations of propofol did not affect HPV and high concentrations of propofol inhibited HPV. The pretreatment of L-NAME and glibenclamide did not alter the inhibition of HPV even at high concentrations of propofol. CONCLUSIONS: The EDRF and ATP-dependent K+ channel did not largely contribute to baseline pulmonary arterial tone but EDRF might be released and downregulate HPV. Clinical concentrations of propofol did not inhibit HPV but high concentrations of propofol inhibited HPV. In addition, the mechanism of inhibition of HPV at high concentrations of propofol did not relate to the EDRF pathway and ATP-dependent K+ channel.
Animals ; Arterial Pressure ; Endothelium-Dependent Relaxing Factors ; Glyburide* ; Lung* ; NG-Nitroarginine Methyl Ester* ; Propofol* ; Rats* ; Vasoconstriction*

BACKGROUND: The relaxative response of blood vessels to acetylcholine (ACh) is known to be abnormal in diabetic rat due to changes in endothelium-derived relaxing factor (EDRF) and/or endothelium-derived hyperpolarizing factor (EDHF)-mediated action. Oxygen free radical (OFR) interferes with endothelium dependent relaxation to ACh in diabetic rats; this effect rnay be prevented by superoxide dismutase (SOD), OFR scavenger. Then, we determined the effect of SOD on modulation of OFR-induced damage to EDRF and EDHF-mediated relaxations to ACh in diabetic rat aortas. METHODS: After aortas were incubated with free radical generating system for 15 min with or without SOD pretreatment (150 U/mL) and contracted submaximally by norepinephrine (10 (-5) M), relaxative responses to cumulative concentrations (10 (-9) M to 10 (-5) M) of ACh were measured in aortas isolated from the control and 6-8 week streptozotocin-induced diabetic rat. We measured relaxative responses to ACh in these aortas treated with calmidazolium (100uM) or N-nitro-L-arginine methyl ester (luM) after exposure to OFR with/without SOD pretreatment, RESULTS: The ACh-induced relaxation (10 (-9)M to 10 (-5) M) was significantly decreased in diabetic than in control rat aortas (p<0.05). ACh-induced relaxation in diabetic rat aortas was significantly impaired from 79.3% to 71.2% after exposure to OFR (p<0.05), and the degree of ACh-induced relaxation was recovered from 71.2% to 84.0% after pretreatment with SOD (p<0.05). EDRF-mediated relaxation to ACh in diabetic rat aortas was significantly impaired from 71.2% to 61.6% after exposure to OFR (p<0.05), and the degree of impairment of ACh-induced EDRF-mediated relaxation was recovered from 61.6% to 76.0% after pretreatment with SOD. After exposure to OFR, EDHF-mediated relaxation to ACh in diabetic rat aortas was not significanlty impaired. However, the degree of impairment of EDHF-mediated relaxation to ACh was recovered from 46.0% to 59.5% after pretreatment with SOD. CONCLUSION: This study suggests that OFR may impair mainly EDRF-mediated relaxation to ACh and SOD may protect rnainly OFR-induced damage to EDRF-mediated relaxation to ACh in diabetic rat aortas.
Acetylcholine ; Animals ; Aorta* ; Blood Vessels ; Endothelium ; Endothelium-Dependent Relaxing Factors ; Free Radicals* ; Norepinephrine ; Oxygen* ; Rats* ; Relaxation* ; Superoxide Dismutase* ; Superoxides*

BACKGROUND: Coronary artery spasm plays an important role in the pathogenesis of variant angina (VA). Prostacyclin is one of the endothelium derived relaxing factors. The association between the novel single nucleotide polymorphism in the prostacyclin synthase gene and VA is not known. Therefore, we investigated the association between VA and the polymorphysm in the prostacyclin synthase gene. METHODS: We compared 45 variant angina patients who had positive intravenous ergonovine test by coronary angiography with 59 control subjects who had negative intravenous ergonovine test and normal coronary angiogram. Using the polymerase chain reaction-single-strand conformation polymorphism analysis, we identified a single nucleotide polymorphism, C1117A, in exon 8. This nucleotide change did not cause an amino acid change in codon 373. RESULTS: There was no significant difference in characteristics between the control group and the VA group, and there was no significant difference in the genotype distributions between the control group and the VA group. CONCLUSION: The C1117A polymorphism in exon 8 of the prostacyclin synthase gene is not associated with variant angina.
Codon ; Coronary Angiography ; Coronary Vessels ; Endothelium-Dependent Relaxing Factors ; Epoprostenol* ; Ergonovine ; Exons ; Genotype ; Humans ; Polymorphism, Single Nucleotide ; Spasm

BACKGROUND: Desflurane is a new inhaled anesthetic with the lowest blood/gas partition coefficient and enflurane is one of the major anesthetics in these days. But the effect of volatile anesthetics and the site of action on the blood vessel are still controversial. Since Furchgott (1980) discovered endothelium derived relaxing factor (EDRF) from endothelium, many investigators have studied about the relationship between the EDRF and the effect of the volatile anesthetics on blood vessels. In this study, we evaluated that the effect and the action site of enflurane and desflurane on isolated aortic rings of the rabbit. METHODS: Each of obtained thoracic aorta from rabbits (1.5~2.5 kg) was divided into 4~6 mm rings, and a half of that were denuded. All of the aortic rings were preconstricted with phenylephrine 1.5 10-7 Mole in warm organ bath filled with modified Krebs' solution, and then LNAME (inhibitor of nitric oxide synthase, 3 10-4Mole) was administered to one group of aortic rings. MB (inhibitor of soluble guanylyl cyclase, 2 10-5Mole) was administered to another one group and neither of LNAME nor MB was administered to the other group. And then enflurane (1%, 2%, 3%, 4%) or desflurane (6%, 9%, 12%) was administered to all of aortic rings. The polygraph recorded the changes of tension of aortic ring which was transmitted through the force transducer. RESULTS: It was proved that basal EDRF was released from endothelium by the fact that intact aortic rings were more constricted after LNAME or MB administration. The intact aortic rings were constricted in all concentration of enflurane and both intact and denuded rings were maintained from control tension in all concentrations of desflurane. CONCLUSION: It is concluded that enflurane in all concentrations has an endothelium-mediated vasoconstriction effect and desflurane in all concentrations has no effect on isolated aortic rings of rabbit.
Anesthetics ; Aorta, Thoracic ; Arginine* ; Baths ; Blood Vessels ; Endothelium ; Endothelium-Dependent Relaxing Factors ; Enflurane* ; Guanylate Cyclase ; Humans ; Nitric Oxide Synthase ; Phenylephrine ; Rabbits ; Research Personnel ; Transducers ; Vasoconstriction

BACKGROUND: Patients with essential hypertension have abnormal endothelium-dependent vasodilation due to reduced release of nitric oxide(NO). But it is uncertain whether this defect is selective for some pathways of nitric oxide production or a more generalized abnormality of endothelial function. The purpose of this study was to determine whether this defect is due to an impairment at the specific intracellular signal-transduction pathway level or is a more generalized endothelial dysfunction METHOD: Forearm blood flow was measured in 10 patients with essential hypertension (mean blood pressure, 129+/-16.6mmHg ; aged 48+/-10 years old) and 10 control subjects(mean blood pressure, 99.7+/-6.6mmHg ; aged 41+/-10 years old) using strain-gauge plethysmography. The endothelium-dependent vasodilators were acetylcholine(7.5, 15, and 30ug/min), which uses a pertussis toxin-sensitive signal transduction pathway, and bradykinin(100, 200, and 400ng/min), which uses a pertussis toxin-insensitive signal transduction pathway to activate nitric oxide production. Sodium nitroprusside(0.8, 1.6, and 3.2ug/min) was used as an endothelium-independent vasodilator. All drugs were infused into the brachial artery and the order was determined randomly. RESULTS: The maximum flow in response to acetylcholine was markedly impaired in hypertensive patients compared with control subjects(5.29+/-1.86 vs 11.04+/-2.46ml/min/100ml forearm tissue, p<0.001). But the maximum forearm blood flow in response to bradykinin was similar in the two groups(11.96+/-3.57 vs 12.48+/-1.92ml/min/100ml forearm tissue, p=0.69) and that in response to sodium nitroprusside was also similar(10.63+/-3.74 vs 10.51+/-2.39ml/min/100ml forearm tissue, p=0.94). CONCLUSION: Patients with essential hypertension have impaired endothelium-dependent vasodilator response only to acetylcholine, while the response to bradykinin is preserved. This finding indicates that the impairment of endothelial vasodilator function is selective, and suggests the defect occurs at the level of the intracellular signal transduction pathway.
Acetylcholine ; Blood Pressure ; Brachial Artery ; Bradykinin ; Endothelium ; Endothelium-Dependent Relaxing Factors ; Forearm ; GTP-Binding Proteins ; Humans ; Hypertension* ; Nitric Oxide ; Nitroprusside ; Plethysmography ; Signal Transduction ; Sodium ; Vasodilation* ; Whooping Cough

BACKGROUND: Many studies reported that endothelium-dependent vasodilator response is impaired in patients with congestive heart failure. But the opposite results also were reported. The aim of this study was to determine the presence of endothelial dysfunction and its characteristics. METHODS AND MATERIALS: Forearm blood flow was measured in 12 patients with congestvie heart failure (7 males and 5 females, mean age 53+/-11 years old) and 10 normal control subjects (5 males and 5 females, mean age 41+/-10 years old) using strain-gauge plethysmography. The endothelium-dependent vasodilators were acetylcholine (7.5, 15, and 30 microgram/min), which uses a pertussis toxin-sensitive signal transduction pathway, and bradykinin (100, 200, and 400 ng/min), which uses a pertussis toxin-insensitive signal transduction pathway to activate nitric oxide production. Sodium nitroprusside (0.8, 1.6, and 3.2 microgram/min) was used as an endothelium-independent vasodilator. All drugs were infused into the brachial artery with random order. RESULTS: The basal forearm blood flow was similar between both groups. The maximum flow in response to acetylcholine, bradykinin, and sodium nitroprusside was also similar in two groups. CONCLUSIONS: Patients with congestive heart failure showed normal endothelium-dependent vasodilator responses to both acetylcholine and to bradykinin. This finding indicates that the endothelial vasodilator function is normal in the patients with heart failure.
Acetylcholine ; Brachial Artery ; Bradykinin ; Endothelium ; Endothelium-Dependent Relaxing Factors ; Estrogens, Conjugated (USP)* ; Female ; Forearm ; Heart Failure* ; Humans ; Male ; Nitric Oxide ; Nitroprusside ; Plethysmography ; Signal Transduction ; Vasodilation* ; Whooping Cough

Relaxation of penile cavernous smooth muscle is controlled by nerve and endothelium derived substances. Externally applied acetylcholine in human corpus cavernosum has been shown to cause endothelium dependent smooth muscle relaxation and nitric oxide(NO) is known as an endothelium derived relaxing factor(EDRF). NO has been identified as an endothelium derived relaxing factor in blood vessels. We tried to determine whether it is involved in the relaxation of the corpus cavernosum that allows penile erection. The changes of isometric tension in rabbit cavernous smooth muscle strips mounted in organ bath chambers after the addition of drugs were monitored on the biophysical recording system. Acetylcholine induced a dose-dependent relaxation and atropine at 5 x 10(-5) M almost abolished the effects of acetylcholine. N(c)-nitro-L-arginine (L-NOARG) at 5 x 10(-5) M almost abolished the effects of acetylcholine. The subsequent addition of L-arginine at 5 x 10(-5) M further restored to the effect of acetylcholine, but these effect did not occur if D -arginine was substituted for L-arginine. Methylene blue at 10-5 M markedly inhibited effects of acetylcholine. These data suggest that acetylcholine endothelial formation of NO via muscarinic receptor and NO from L-arginine leads to the relaxation of cavernous smooth muscle via activation of guanylate cyclase in rabbit.
Acetylcholine ; Arginine ; Atropine ; Baths ; Blood Vessels ; Endothelium ; Endothelium-Dependent Relaxing Factors ; Guanylate Cyclase ; Humans ; Male ; Methylene Blue ; Muscle, Smooth* ; Nitric Oxide* ; Penile Erection ; Receptors, Muscarinic ; Relaxation*