Effects of Glibenclamide and L-NAME on Hypoxic Pulmonary Vasoconstriction in Rats / 대한마취과학회지

BACKGROUND: This study was performed with NW-nitro-L-arginine methyl ester ((L)-NAME), an inhibitor of EDRF production, and glibenclamide, which closes ATP dependent K+ channels, to determine their effects on hypoxic pulmonary vasoconstriction in isolated perfused rat lungs ventilated with normoxia (21% O2, 5% CO2, balanced N2) and hypoxia (5% O2, 5% CO2, balanced N2). METHODS: Thirty male Sprague-Dawley rats (250 - 350 g) were divided into the control group (n = 10), glibenclamide group (n = 10), and (L)-NAME group (n = 10). In the control group, after the lungs were isolated and stabilized, they were exposed to angiotensin II and 3 consecutive hypoxias. In glibenclamide group, they were exposed to angiotensin II and 3 consecutive hypoxias, and exposed to 3 more hypoxias after injection of glibenclamide 10 uM. In the (L)-NAME group, they were exposed to angiotensin II and 3 consecutive hypoxias, and exposed to 3 more hypoxias after injection of (L)-NAME 100 uM. RESULTS: Hypoxic pulmonary vasoconstriction (deltaPpa) after the (L)-NAME 100nM injection was 12.5 +/- 1.1 mmHg, and it was significantly greater than that of the control group 4.2 +/- 1.1 mmHg (P < 0.05). Hypoxic pulmonary vasoconstriction (deltaPpa) after glibenclamide 10nM injection was 5.3 +/- 1.1 mmHg, and there was no difference with the control group, 4.2 +/- 1.1 mmHg. CONCLUSIONS: We concluded that (L)-NAME, an inhibitor of EDRF production, significantly increased hypoxic pulmonary vasoconstriction, but glibenclamide, which closes ATP dependent K+ channels, did not affect hypoxic pulmonary vasoconstriction in this model.

Effects of Nitric Oxide Synthase Inhibitior on Energy Metabolism in Acute Ischemic-Reperfused Cat Brain: Investigated by 31P and 1H Magnetic Resonance Spectroscopy / 대한마취과학회지

BACKGROUND: The effects of the inhibitor of nitric oxide synthase (NOS) in cerebral ischemia have been debated. Recently, it has been suggested that it depends on the amount of the inhibitor used. Therefore, this study was carried out to evaluate the effects of the NOS in the acute ischemia-reperfusion of the cat model using variable amounts of the inhibitor. METHODS: Nineteen cats were divided into 3 groups: group 1 (n = 6), 10 mg/kg of N-nitro-L-arginine methyl ester (L-NAME); group 2 (n = 7), 0.5 mg/kg; group 3 (n = 6), control group. Incomplete global cerebral ischemia was induced by ligation of both carotid arteries with arterial hypotension (-40 mmHg) for 30 minutes followed by 3 hours of reperfusion. The NOS inhibitor (L-NAME), was injected intraperitoneally 5 minutes before reperfusion. 31P and 1H MR spectroscopy were performed. A series of spectra was acquired in the time intervals before ligation, during ischemia, and after reperfusion. RESULTS: Phosphocreatine/inorganic phosphate (PCr/Pi) ratios for group 1 were significantly lower than for groups 2 and 3 (P < 0.05), and there was no significant difference between groups 2 and 3. Lactate/N-acetyl aspartate (Lac/NAA) and lactate/creatine (Lac/Cr) ratios at 180 minutes after reperfusion were higher for group 1 than for groups 2 and 3 (P < 0.05). There were no significant differences in pH and lactate/choline (Lac/Cho) ratios among the 3 groups. CONCLUSIONS: It is demonstrated that the effect of the NOS inhibitor is dosage dependent. A high dose (10 mg/kg) of L-NAME seems to have an adverse effect on recovery of the ischemia, but a low dose (0.5 mg/kg) seems to have no effect.

Effects of Inhibition of Endogenous Nitric Oxide System on Regional Myocardial Function and Systemic Hemodynamics in Anesthetized Dogs / 대한마취과학회지

BACKGROUND: The present study was aimed (1) to assess the effects of nitric oxide (NO) synthesis inhibitor on regional myocardial function and systemic and pulmonary hemodynamics; (2) to determine whether the blockade of the cyclo-oxygenase (COX) pathway modifies these effects on the variables, and (3) to investigate the mechanism of cardiac depression following NO synthesis inhibition in an open-chest canine model. METHODS: Twenty-five dogs of either sex were acutely instrumented under 1.6% ethrane anesthesia to measure aortic, pulmonary arterial and left ventricular pressure, pulmonary (cardiac output) and left circumflex coronary flow, and subendocardial segment length. NG-nitro-L-arginine methyl ester (L- NAME) at doses of 0.3, 1.0, 3.0, or 10.0 mg/kg i.v. was administered alone (control dogs, n = 10) or in the presence of COX inhibitor, indomethacin (10 mg/kg i.v., n = 10). Seven dogs (n = 7) received phenylephrine at doses of 0.1, 0.3, 1.0, or 3.0 microgram/kg/min i.v. to compare its hemodynamic effects with those of L-NAME. The preload recruitable stroke work slope (Mw) and percent systolic shortening (%SS) as an index of regional myocardial contractility, and the maximum segment lengthening rate (dL/dt max) and percent post-systolic shortening (%PSS) as an index of regional diastolic function, were evaluated. RESULTS: L-NAME dose-dependantly attenuated both regional systolic (Mw and %SS) and diastolic functions (dL/dt max and %PSS), whereas it caused an increase of coronary flow. L-NAME dose- dependently increased systemic blood pressure and vascular resistance as well as pulmonary arterial pressure and vascular resistance. L-NAME also reduced cardiac and stroke volume indices. Pretreatment with indomethacin did not affect the regional myocardial and systemic hemodynamic responses to L-NAME, but did blunt the coronary flow and pulmonary pressure responses. The magnitude of decreases in cardiac and stroke volume indices and Mw was greater with L-NAME than with phenylephrine (P <0.05), despite the comparable blood pressure increases. CONCLUSIONS:These results suggest (1) that NO plays a significant role in cardiac function as well as in systemic and pulmonary but not coronary, vasomotor activities, and (2) that COX products are involved in pulmonary hemodynamic responses to NO synthesis inhibition. It is also suggested that the decline in cardiac output following the NO synthesis inhibition results from a direct myocardial depressant effect of the drug.