Acute and chronic inhibition of nitric oxide synthase in conscious rabbits: role of nitric oxide in the control of vascular tone

Acute and chronic effects of Nw-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide synthase, were examined on the hindquarter hemodynamics of conscious rabbits. After pharmacological autonomic reflex blockade on four experimental days (days 0, 1, 2, and 7), responses to aortic occlusion (balloon cuff, 5-80 s inflation), intra-aortic infusion of acetylcholine, adenosine, and sodium nitroprusside (SNP) were measured before and after vehicle (day 0) or L-NNA (16 mg/kg/h i.v., days 1, 2, and 7). On day 1, L-NNA raised the mean arterial pressure (MAP), and lowered the heart rate (HR) and hindquarter vascular conductance (HVC = abdominal aortic Doppler blood flow/MAP). On days 2 and 7, L-NNA only slowly raised the MAP. The dilator response to acetylcholine was inhibited by L-NNA on day 1 and before and after L-NNA on days 2 and 7. The responses to aortic occlusion, adenosine, or SNP infusion were unaffected by L-NNA treatment on any day. Thus, if nitric oxide synthase inhibition by L-NNA abolishes NO release, then (i) reactive hyperaemia is independent of NO, (ii) basal NO release normalises the arterial pressure in the short term but other factors become important in the long term, and (iii) the blockade by L-NNA of receptor-stimulated NO release by acetylcholine is only very slowly reversible.     

Sarcoidosis and thyrotoxicosis: A study of five patients

Regional blood flow of the gastrointestinal (GI) tract and cardiac output have been determined in male Sprague-Dawley rats weighing from 30-726 g. The cardiac output (ml/min per kg) was highest in rats weighing 80-100 g. In heavier rats the cardiac output decreased proportionally with the body weight. The gradient of blood flow to the different parts of the GI tract develops step by step. In the weaning period the blood flow (ml/min per g tissue) through the stomach was less than that through the distal parts of the GI tract. However, the blood flow through the small intestine, cecum and large intestine was uniform at this age. In rats weighing 80-100 g the blood flow through both the cecum and large intestine was less than that through the small intestine. The gradient in blood flow through the various segments of small intestine developed last.     

NO does not mediate inhibitory neural responses in sheep airway and bronchial vascular smooth muscle

Endogenous nitric oxide (NO) influences acetylcholine-induced bronchovascular dilation in sheep and is a mediator of the airway smooth muscle inhibitory nonadrenergic, noncholinergic neural response in several species. This study was designed to determine the importance of NO as a neurally derived modulator of ovine airway and bronchial vascular smooth muscle. We measured the response of pulmonary resistance (RL) and bronchial blood flow (Qbr) to vagal stimulation in 14 anesthetized, ventilated, open-chest sheep during the following conditions: 1) control; 2) infusion of the alpha-agonist phenylephrine to reduce baseline Qbr by the same amount as would be produced by infusion of Nomega-nitro-L-arginine (L-NNA), a NO synthase inhibitor; 3) infusion of L-NNA (10(-2) M); and 4) after administration of atropine (1.5 mg/kg). The results showed that vagal stimulation produced an increase in RL and Qbr in periods 1, 2, and 3 (P < 0.01) that was not affected by L-NNA. After atropine was administered, there was no increase in Qbr or RL. In vitro experiments on trachealis smooth muscle contracted with carbachol showed no effect of L-NNA on neural relaxation but showed a complete blockade with propranolol (P < 0.01). In conclusion, the vagally induced airway smooth muscle contraction and bronchial vascular dilation are not influenced by NO, and the sheep's trachealis muscle, unlike that in several other species, does not have inhibitory nonadrenergic, noncholinergic innervation.     

Hemodynamic effects of sub-chronic NO synthase inhibition in conscious dogs: role of EDRF/NO in muscular exertion

Acute and chronic administration of nitric oxide (NO) synthase (NOS) inhibitors increase mean arterial blood pressure (MAP) in rats but their hemodynamic effects in other species remain unknown. Moreover, the role of NO in the control of exercise-induced vasodilation is still debated. To answer these questions, six dogs were instrumented for the continuous measurement of cardiac output (CO, electromagnetic flow probe on the aorta), MAP (aortic catheter) and left ventricular pressure (Konigsberg gauge). Total peripheral resistance (TPR) was calculated as MAP/CO ratio and dP/dt was used as an index of cardiac inotropism. The dogs were treated from day 0 (D0) to 7 (D7) by the NOS inhibitor, N omega-nitro-L-arginine (L-NNA), 20 mg/kg/day (IV). Such a dose regimen resulted in NOS inhibition evidenced (a) in vivo by a reduction of the hypotensive responses to graded doses of acetylcholine and bradykinin, (b) ex vivo by a decrease in the relaxation of the femoral artery to acetylcholine (EC 50 = 2.2 +/- 0.6 10(-7) M after L-NNA vs 2.2 +/- 0.8 10(-8) M in controls). One month after instrumentation, the dogs being conscious, MAP measured at rest remained unchanged following one week L-NNA treatment (from 90 +/- 2 at D0 to 91 +/- 5 mmHg at D7). However, TPR increased (from 3,600 +/- 290 at D0 to 6,300 +/- 510 dyn.s.cm-5 at D7) and CO decreased (from 2.1 +/- 0.2 at D0 to 1.2 +/- 0.1 l/min at D7) (all p < 0.01), partly as the result of a marked bradycardia (from 100 +/- 7 at D0 to 60 +/- 7 beats/min at D7). L-NNA induced-increase in TPR was completely reversed by a bolus injection of nitroglycerin (10 micrograms/kg). During treadmill exercise (12 km/h), heart rate (251 +/- 9 at D0 vs 226 +/- 11 beats/min at D7), CO (6.3 +/- 0.9 at D0 vs 4.3 +/- 0.7 l/min at D7) and stroke volume remained significantly lower, and TPR significantly higher (1,662 +/- 278 at D0 vs 2,621 +/- 489 dyn.s.cm-5 at D7) after L-NNA than in the control state. Thus, NOS inhibition in resting conscious dogs by L-NNA markedly increases peripheral resistance but does not increase arterial pressure. In addition, L-NNA blunts both exercise-induced peripheral vasodilation and increase in cardiac output, despite metabolic vasodilation.     

Nitric oxide mediates intestinal hyperaemic responses to intraluminal bile-oleate

It has long been recognized that intestinal blood flow increases at mealtimes. Mesenteric hyperaemia is also evoked by activation of sensory peptidergic nerves. Our studies explored the possible role of endogenous nitric oxide (NO) in the rat intestinal vasodilator response to luminal instillation of an oleic acid plus bile mixture before and after acute intrajejunal instillation of capsaicin and after chronic pretreatment with capsaicin. In anaesthetized rats we measured jejunal blood flow (BF) with an ultrasonic Doppler flowmeter and systemic arterial pressure (AP) with a pressure transducer. Intestinal perfusion with 80 mM oleic acid in bile increased BF by 98 +/- 12%. Instillation of 4 mg of capsaicin into the jejunal lumen initially increased BF by 42 +/- 9% but was followed by vasoconstriction. Inhibition of NO synthase with 25 mg/kg i.v. N-nitro-L-arginine (L-NNA) decreased BF by 27 +/- 5% and increased AP by 37 +/- 11%. After treatment with L-NNA and after acute and chronic administration of capsaicin, the bile-oleate-induced maximal increases in BF above control levels were 42 +/- 7%, 65 +/- 12%, and 58 +/- 8%, respectively. The observed inhibitory effect of L-NNA on the intestinal hyperaemic response to the bile-oleate mixture was reversed by pretreatment with L-arginine (100 mg/kg i.v.). In capsaicin pretreated rats the subsequent bile-oleate-induced hyperaemia was reduced in magnitude but the inhibitory effects of L-NNA were proportionately the same as in animals not receiving capsaicin. These findings support the hypothesis that NO is involved with bile-oleate-induced mesenteric hyperaemia.     

Effects of microinjection of L-NNA and SNP into ventrolateral medulla on blood pressure, heart rate and renal sympathetic nerve activity in rats

The effects of microinjection of a NO synthase inhibitor--N-nitro-L-arginine (L-NNA) and NO donor-sodium nitroprusside (SNP) into ventrolateral medulla on blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were examined in anesthetized rats to define the role of L-arginine: NO pathway in the central regulation of BP and to explore the underlying mechanism. The results obtained were as follows: (1) Following microinjection of L-NNA into rostral ventrolateral medulla (RVLM), both of MAP and RSNA were increased. The effects lasted for more than 30 min and could be reversed by prior intravenous injection of L-arginine. (2) In response to microinjection of SNP into RVLM, MAP and RSNA were decreased, while HR showed no significant change. (3) During microinjection of L-NNA into caudal ventrolateral medulla (CVLM), MAP, HR and RSNA were decreased. (4) Upon injection of SNP into CVLM, MAP and RSNA were increased, but HR showed no significant change. The above-mentioned results indicate that the L-arginine: NO pathway may exhibit a modulatory action on the activity of ventrolateral medulla neurons.     

Cerebral blood flow is increased throughout 12 h of hypoxaemia in the mid-gestation ovine fetus

The changes in regional cerebral blood flow (CBF) in response to prolonged hypoxaemia were measured using coloured microspheres in the 0.6-gestation ovine fetus (n = 5). Fetal hypoxaemia was induced for 12 h by reducing maternal uterine blood flow with an adjustable clamp. CBF (mL min-1 100 g-1) was increased (P < 0.05) from control values (38.7 +/- 3.5) to 105.6 +/- 5.6 at 6 h of hypoxaemia, and to 121.9 +/- 23.1 at 12 h of hypoxaemia. One hour after fetal hypoxaemia had ceased, CBF (54.0 +/- 3.3) had decreased (P < 0.05) towards control values indicating incomplete cardiovascular recovery. Cerebral vascular resistance at 6 h and 12 h of hypoxaemia was lower (P < 0.05) than control values, and returned to control values 1 h after fetal hypoxaemia had ceased. Cerebral oxygen delivery at 6 h and 12 h of hypoxaemia was not significantly different from control values, but was higher (P < 0.05) 1 h after hypoxaemia had ceased. It is concluded that CBF is sufficiently increased during prolonged hypoxaemia in the mid-gestation fetus to maintain cerebral oxygen delivery.     

Single-tube mixed agglutination test for the detection of staphylococcal protein A

Intra-arterial and intravenous catheters were inserted in six fetal lambs at 125-130 days of gestation. On the following day, fetal arterial pressures and blood gases were monitored and fetal cardiac output and its distribution were measured by injection of radionuclide-labeled microspheres 15 mum in diameter. Acetylsalicylic acid, 55-90 mg/kg of estimated fetal weight, then was administered into the fetal stomach. Fetal pulmonary arterial pressure rose significantly after an average of 58 minutes, increasing the pressure difference between the pulmonary artery and the aorta from 2 +/- 0.3 (SEM) mm Hg during control to 11.2 +/- 1.6 mm Hg. Resistance across the ductus arteriosus rose from 4.2 +/- 0.5 (SEM) to 27.4 +/- 4.01 units, and flow fell from 495 +/- 44 (SEM) to 409 +/- 20 ml/minute. The proportion of combined ventricular output distributed to the placenta, adrenals, heart, and lungs increased, whereas the proportion of combined ventricular output distributed to the brain, liver, intestine, kidneys, and upper and lower body fell. In two fetuses infusion of prostaglandin E1 reversed the pulmonary hypertension. Inhibition of prostaglandin synthesis in fetal lambs produced constriction of the ductus arteriosus and redistribution of cardiac output. It is probable that prostaglandins, particularly E1, are involved in regulation of blood flow through the ductus arteriosus and various vascular beds in the normal resting fetus.     

Topical clonidine for orofacial pain: a pilot study

BACKGROUND: To preserve postoperative digestive function in patients with esophageal carcinoma, jejunal or colonic segments on long vascular pedicles are transplanted and anastomosed between the esophagus and residual stomach. A postoperative survey showed pedicled jejunum transplantation to be superior in terms of digestive and absorptive functions, intraesophageal pressure, pH, and the quality of life of long-term postoperative survivors. Anastomotic leakage and necrosis of the pedicled intestinal graft are occasional complications; circulatory disorders of the pedicled intestine are a probable cause of both complications. STUDY DESIGN: To simulate pedicled jejunum transplantation, we prepared pedicled colonic segments from dogs and measured blood flow volume at the cut end of the oral side of the colonic segments using the hydrogen clearance method and at the nutrient vascular pedicle with an electromagnetic blood flowmeter. RESULTS: Resection of excess colon increased blood flow volume per unit weight of the colonic segment. CONCLUSIONS: It is essential to resect excess intestine and keep only the minimum length of pedicled intestinal graft needed for reconstruction of the esophagus.     

Human salivary sugar clearance after sugar rinses and intake of foodstuffs

Effects of chronic intraluminal amylase inhibition on eating and the digestive system are unclear. In growing rats, we determined the effect of ingesting a wheat amylase inhibitor (AI) on eating, weight, small intestinal mucosal growth, and disaccharidases. Three groups of 12 rats received AI, were pair-fed controls (PFC), or had free access to food (FAC). After measuring food intake and body and stool weight for 21 d, rats were decapitated and the small intestine was divided into four segments. AI and PFC rats had similar food intake, weight gain, and stool output, but these were less than FAC rats (P < 0.005). AI rats ate less (P < 0.001) than PFC during the light cycle and less than FAC rats during darkness. Mucosal DNA and RNA were reduced (P < 0.05) in the upper small intestine of AI and PFC rats compared with FAC rats. Mucosal weight, RNA, and disaccharidase activities were greater (P < 0.01) in the ileum of AI rats compared with PFC and FAC rats. AI alters the amount and pattern of food intake, reduces weight gain, upper small intestinal mucosal weight, protein and DNA, and increases distal small intestinal mucosal weight, RNA, and disaccharidases. AI likely causes these effects by inducing satiety and increasing carbohydrate delivery to the distal intestine.     

In vitro study of the effect of miglitol on carbohydrate digestion and intestinal metabolism in normal and non-insulin-dependent diabetic rats

The effect of miglitol was studied (20 mg/kg body weight), administered intraduodenally alone or together with maltose, on the absorption and intestinal metabolism of glucose during its translocation from the lumen of the intestine to the blood, using in vitro perfused preparations of complete small intestine-pancreas, proximal small intestine alone, or distal small intestine alone, isolated from normal and non-insulin-dependent diabetic rats. In the absence of a luminal administration of maltose in normal rats, the glucose uptake from the vascular perfusate was greater in the presence (0.52 +/- 0.04 mmol/h) than in the absence (0.39 +/- 0.02 mmol/h) of miglitol (p < 0.05). In diabetic rats, no significant variations were observed in glucose uptake from the vascular perfusate as an effect of miglitol, but the glucose uptake in the presence of this drug was significantly less (p < 0.05) than that observed in normal rats. Portal lactate was significantly greater (p < 0.05) in diabetic than in normal rats and, after administration of miglitol, rose in both normal and diabetic rats, the rise being significantly greater in normal than in diabetic rats (p < 0.01). When maltose was administered luminally (2 g/kg body weight), the values of portal glucose in both normal and diabetic rats were significantly less in the presence of miglitol in the complete as well as in the distal and proximal small intestine preparations (p < 0.05); the glucose uptake from luminal administered maltose was greater in the presence of miglitol in diabetic (p < 0.05) and in normal (p < 0.05) rats except in the complete small intestine of normal rats; and no significant differences were observed in portal lactate levels between normal and diabetic rats in the presence of miglitol. In conclusion, our results show that miglitol administered luminally at the doses employed here, as well as reducing the transport of glucose from the lumen of the intestine into the blood supply, significantly stimulate intestinal glucose metabolism.     

Contribution of endogenous endothelin-1 to the maintenance of vascular tone: role of nitric oxide

Studies were designed to compare the effect of the nitric oxide inhibitor, N omega-nitro-L-arginine (L-NNA), and the novel ETB receptor antagonist, RES-701-1, on changes in blood pressure and renal blood flow induced by exogenous endothelin receptor agonists and to determine the effect of L-NNA on basal hemodynamics in conscious, chronically instrumented rats. Infusion of low (nonpressor) doses of L-NNA or RES-701-1 potentiated systemic and renal vasoconstriction induced by bolus injections of endothelin-1 or sarafotoxin 6c. Bolus intravenous injection or sustained infusion of L-NNA alone resulted in dose-dependent increases in blood pressure and decreases in renal blood flow, similar to our recently reported results with RES-701-1. Vasoconstriction induced by inhibition of nitric oxide was attenuated by SB 209670, a mixed ETA/B receptor antagonist, but not by BQ123, an ETA receptor antagonist; neither antagonist altered basal hemodynamics. Collectively, the results indicate that: (1) endothelin plays an important role in the control of basal vascular tone by mediating both vasodilation and vasoconstriction; (2) these effects are mediated by different ETB receptor subtypes in the rat, one located on the endothelium that mediates vasodilation via the nitric oxide pathway, the other located on the vascular smooth muscle that mediates contraction.     

An autopsied case of multiple system atrophy with remarkable cerebral atrophy

OBJECTIVES: We tested the effects of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, on plasma levels of interleukin (IL) IL-6, IL-8, tumor necrosis factor-alpha (TNFalpha) and nitrite/nitrate (NO2-/ NO3-) in patients with severe septic shock. DESIGN: Prospective clinical study. SETTING: Surgical intensive care unit at a university hospital. PATIENTS: 11 consecutive patients with severe septic shock. INTERVENTIONS: Standard hemodynamic measurements were made and blood samples taken at intervals before, during, and after a 12-h infusion of L-NAME 1 mg x kg(-1) x h(-1) for determination of plasma IL-6, IL-8, TNFalpha and NO2-/NO3- concentration. MEASUREMENTS AND RESULTS: Patients with sepsis had increased plasma levels of IL-6, IL-8, TNFalpha and NO2-/NO3- (p < 0.05). Plasma levels of IL-6. IL-8, and NO2-/NO- were negatively correlated with systemic vascular resistance (r = -0.62, r = -0.65, and r = -0.78, respectively, all p < 0.05). Continuous infusion of L-NAME increased mean arterial pressure and systemic vascular resistance, with a concomitant reduction in cardiac output (all p < 0.01). No significant changes were seen in levels of plasma IL-6, IL-8, and NO-/NO3- during the 24-h observation period. Plasma levels of TNFalpha were significantly reduced during L-NAME infusion compared to baseline (p < 0.05). CONCLUSIONS: NO plays a role in the cardiovascular derangements of human septic shock. Inhibition of NO synthesis with L-NAME does not promote excessive cytokine release in patients with severe sepsis.     

Renovascular interaction of epinephrine, dopamine, and intraperitoneal sepsis

OBJECTIVE: To determine the effect of intraperitoneal sepsis on the systemic and renal actions of the continous infusion of epinephrine or dopamine, and during the concurrent administration of both drugs. DESIGN: Prospective, randomized study. SETTING: Laboratory at a university hospital. SUBJECTS: Seven conscious, chronically catheterized, adult merino sheep. INTERVENTIONS: Epinephrine at 40 micrograms/min or dopamine at 2 micrograms/kg/min, or both drugs concurrently were infused for 4 hrs on separate study days in healthy sheep. This protocol was then repeated following the induction of sepsis after the intraperitoneal injection of 10(11) Escherichia coli, 10(12) Bacteroides fragilis, and bran. MEASUREMENTS AND MAIN RESULTS: Systemic oxygen delivery (DO2) and consumption were measured using thermodilution cardiac output and measured oxygen content. Renal blood flow was measured using an electromagnetic flow transducer, and creatinine clearance was calculated as the quotient of renal blood flow and the renal extraction ratio of creatinine. Infusion of epinephrine augmented systemic DO2 and mean arterial pressure (MAP) during both healthy and septic studies. Systemic oxygen consumption was only increased during epinephrine infusion in the septic study. During the healthy animal study, renal blood flow was initially decreased during epinephrine infusion, but increased to 36% above baseline (p = .003). However, creatinine clearance remained unchanged. During the experimental sepsis study, the infusion of epinephrine had less marked effects on renal blood flow (unchanged from baseline), while an initial reduction (15 mins) in creatinine clearance (p = .04) was not sustained and had returned to baseline by 3 hrs. Dopamine alone produced no change in systemic oxygen variables or MAP during the studies on healthy or septic animals. Although dopamine produced renal vasodilation and an increase in renal blood flow in the healthy state, these results were not found during the septic state. In addition, concurrent infusion of dopamine with epinephrine did not alter the systemic or renal effects of epinephrine during the healthy or septic states. CONCLUSIONS: These results do not support the routine use of low-dose dopamine, and demonstrate a change in renovascular responses to catecholamines during intraperitoneal sepsis. The infusion of epinephrine at 40 micrograms/min had few deleterious effects on the kidney, and augmented both MAP and systemic DO2. Its role as a catecholamine in the management of sepsis may need to be reconsidered.     

Participation of nitric oxide in the mucosal injury of rat intestine induced by ischemia-reperfusion

The dual role of nitric oxide as a cytoprotective or a cytotoxic free radical gas has been noted in various types of pathophysiological conditions, including the digestive system. The aim of this study was to examine the role of nitric oxide in the mucosal injury induced by ischemia-reperfusion in the rat small intestine. A transient intestinal ischemia was produced in the catheterized ileal segments of rats by occluding the anterior mesenteric artery for 60 min. Nitric oxide metabolites (NO2- and NO3-) and lactate dehydrogenase activity in perfusates of the intestinal lumen were measured over 5 hr periods. The time-course of histological changes in small intestine was also observed. After ischemia-reperfusion, nitric oxide release in the intestinal lumen increased significantly and the dynamics of nitric oxide release correlated with that of lactate dehydrogenase leakage. The administration of NG-nitro-L-arginine methyl ester (1.0-2.5 mg/kg) inhibited this increased nitric oxide release and the lactate dehydrogenase leakage and afforded protection against the mucosal injury induced by ischemia-reperfusion. In conclusion, the nitric oxide production that was accelerated by ischemia-reperfusion of small intestine may possibly participate in the breakdown of intestinal mucosa after ischemia-reperfusion insult.     

Role of nitric oxide in responses to renin-angiotensin system inhibition in sodium-depleted guinea pig and rat

Previous reports have suggested that NO is an important mediator of the antihypertensive effects of renin-angiotensin system (RAS) inhibition. We examined the effects of the NO synthase inhibitor L-NNA on the hypotensive effects of captopril, the Ang II antagonist EXP 3174, or the renin inhibitor terlakiren. In sodium-depleted guinea pigs (GPs), L-NNA (3 mg/kg) increased MAP by 15-21% for at least 5 hours. L-NNA partially blocked the hypotensive effects of captopril (1 mg/kg, iv), but not those of EXP 3174 (1 mg/kg, iv) or terlakiren (3 mg/kg). In sodium-depleted rats, 10 mg/kg L-NNA (iv) increased MAP by 16-22%, and partially or fully blocked the hypotensive effect of EXP 3174 (1 mg/kg, iv) or captopril (3 mg/kg, iv), respectively. Thus, in contrast to the rat, NO in GPs appears to participate only in the hypotensive action of ACE inhibition and does not appear to be strongly involved in the hypotensive action of AII antagonism or renin inhibition. The involvement of NO in the hypotensive effects of RAS antagonists other than ACE inhibitors may be species-dependent.     

Hepato-splanchnic blood flow and oxygen extraction capabilities during experimental tamponade: effects of endotoxin

We studied the hepato-splanchnic vascular response and changes in O2 extraction capabilities to a reduction in blood flow following endotoxemia. Fourteen anesthetized and mechanically ventilated dogs were divided into two groups of seven each. Group 1 received 2 mg/kg of E. coli endotoxin, and group 2 served as a control. After initial fluid resuscitation following endotoxic shock, regional blood flow estimated by an ultrasonic technique increased similarly in the hepatic artery, portal vein, and mesenteric artery, but microvascular blood flow estimated by a laser Doppler technique was lower in the liver than in the intestinal mucosa. When blood flow was reduced by cardiac tamponade, endotoxin-treated animals had greater whole body and regional critical O2 delivery (DO2crit) and lower whole body, liver, and intestinal critical O2 extraction ratios (O2ERcrit). DO2crit was higher in the liver than in intestine but O2ERcrit was similar in the two organs. Whole body DO2crit at the onset of organ O2 supply dependency was similar under control (9.4 +/- 1.9 mL/kg. min for whole body, 10.3 +/- 4.7 mL/kg. min for liver, and 10.0 +/- 2.6 mL/kg. min for intestine) and endotoxic conditions (13.6 +/- 3.2 mL/kg. min for whole body, 15.6 +/- 2.7 mL/kg. min for liver, and 15.4 +/- 8.7 mL/kg. min for intestine). We conclude that fluid-resuscitated endotoxic shock in dogs is characterized by blood flow redistribution within the liver and intestine. Microvascular depression may be more severe in the liver than in the intestinal mucosa, although the whole body, the liver, and the intestine became O2 supply-dependent simultaneously.     

A study of the mechanism of L-NNA on sleep inhibition]

In the present study, the sleep-waking cycle and the immunoreactivity of 5-HT-containing neurons in rats receiving intraperitoneal injections of N-Nitro-L-arginine (L-NNA, 50 mg/kg) and L-arginine (L-arg, 110 mg/kg) were observed respectively. The results showed that injection of L-NNA suppressed both slow wave sleep (SWS) and rapid eye movement sleep (REMS) and increased mean arterial pressure (MAP). L-arg markedly attenuated MAP, whereas SWS and REMS were unchanged. The effects of L-NNA on sleep and MAP were reversed by preinjection of L-arg. In comparison with control group, the positive cells in dorsal raphe nucleus (DR) and raphe magus nucleus (MnR) increased 2 h after injection of L-NNA. The effect was attenuated by preadministration of L-arg. All these results suggest that L-arg: NO pathway is involved in the regulation of sleep-waking cycle and the increment of the positive immunoreactivity of the 5-HT-containing neurons in the DR may be related to the sleep-suppressive effects induced by L-NNA.     

Quality of life assessment in reflux disease

It has been suggested that inhibitors of nitric oxide synthesis are of value in the treatment of hypotension during sepsis. In this pilot study, we examined the effects of inhibition of nitric oxide synthesis by continuous infusion of N(omega)-nitro-L-arginine methyl ester (L-NAME) at 1.5 mg/kg/h in a patient with severe septic shock. L-NAME produced a rise in mean arterial blood pressure and systemic vascular resistance; catecholamine infusion could be reduced. Parallel to these findings, there was a 50% reduction in cardiac output and a 5-fold rise in pulmonary vascular resistance, which resulted in severe pulmonary hypertension after 3 h of L-NAME infusion, for which the infusion had to be stopped. Following the termination of L-NAME infusion, pulmonary artery pressure and blood pressure returned to baseline values, although pulmonary and systemic vascular resistance remained elevated for several hours. We conclude that nitric oxide appears to play a role in the cardiovascular derangements during human sepsis. Inhibition of nitric oxide synthesis with L-NAME can increase blood pressure and systemic vascular resistance. However, reduced cardiac output and pulmonary hypertension are possible side effects of continuous NO synthase inhibition. These side effects necessitate careful monitoring and may hinder the clinical application of NO synthase inhibitors.