Basal Blood Research Articles

Changes in renal hemodynamics and physiology after normothermic ischemia in animals supplemented with eicosapentaenoic acid.

In order to determine whether treatment of animals with an n-3 fatty acid, eicosapentaenoic acid (EPA), could modify renal hemodynamics and physiology after normothermic ischemia, we studied 42 Spraque Dawley rats orally supplemented with either olive oil or a purified lysine salt of EPA for 4 weeks. Four experimental groups were established. Three groups were treated with increasing doses of EPA: 20 mg/kg per day (EPA 20), 40 mg/kg per day (EPA 40) and 80 mg/kg per day (EPA 80), and one group was supplemented with isovolumetric olive oil (OLI). A control group that received neither EPA nor ischemia was also studied. On day 28, right nephrectomy was performed, followed by 30 min of left renal warm ischemia. Basal arterial pressure and renal blood flow (RBF) were monitored in two kidneys before arterial occlusion and continuously thereafter throughout the experiment in one kidney using an electronic transducer and a flowmeter. From 60 to 120 min after the end of ischemia, urine output (microliter/min), glomerular filtration rate (GFR, microliter/min), measured by inulin clearance, and fractional reabsortion of sodium (FRNa) were determined every 20 min. Renal plasma flow (RPF, ml/min) and renal vascular resistance (VR, mm Hg/ml per min) were calculated. RPF was estimated as RBF (1-hematocrit). Before ischemia, the mean RPF and RBF were higher in EPA-fed than in olive oil-fed animals and after ischemia showed a significantly greater increase in EPA-fed animals than in olive oil-fed animals. Mean VR was lower in EPA-fed animals than in olive oil-fed animals, both before arterial occlusion and after ischemia. Mean urine output was similar in the OLI and EPA 20 groups, and significantly higher in the EPA 40 and EPA 80 groups than in the control group. GFR was significantly lower in the OLI and EPA 20 groups than in the control group. Finally, the EPA 40 group showed a similar and the EPA 80 group a slightly higher GFR than the control group. We conclude that EPA supplementation provides protection from renal ischemic-reperfusion injury, and this effect is more evident at higher EPA doses.

Cardiac oufflow of endothelin, neuropeptide Y and noradrenaline in relation to hyperaemia in coronary sinus flow following electrical conversion of induced ventricular fibrillation in man

The implanted cardioverter defibrillator represents an alternative therapy for patients with drug-refractory malignant ventricular arrhythmias. Implantation and testing of the device requires that ventricular fibrillation be evoked and converted, thus providing a situation in which cardiovascular haemodynamics can be studied. In this study we have evaluated the effects of electrically induced ventricular fibrillation, followed by defibrillation, on coronary sinus blood flow and cardiac outflow of endothelin- and neuropeptide Y-like immunoreactivity (-LI) and of noradrenaline. Twelve patients were studied during implantation of a defibrillator. Ventricular fibrillation was induced and terminated after 17 +/- 1 s 5 +/- 1 times in each patient. In six patients coronary sinus blood flow was measured continuously. Plasma samples were obtained from four of these patients and another six patients, from the coronary sinus, radial artery and central vein before and during fibrillation and at two time points ( < 30 s and 5 min). Basal coronary sinus blood flow decreased to 38% at 14 +/- 2 s of ventricular fibrillation. Immediately following defibrillation there was a short-lasting increase in coronary sinus blood flow to 244% and a significant increase in the levels of neuropeptide Y-LI (146%) and noradrenaline (158%) in the coronary sinus while endothelin-LI remained unchanged (97%). Neither fibrillation nor defibrillation evoked any changes in the peripheral arterial and venous levels of endothelin-, neuropeptide Y-LI or noradrenaline. It is concluded that coronary sinus blood flow is markedly reduced during fibrillation and that restoration of normal impulse activity is followed by short-lasting hyperaemia. There was no evidence for effects on the vascular endothelium as assessed by endothelin levels.

The effect of polycythemia on skin blood flow in hypertensive rats

Polycythemia has marked effects on blood flow through large arteries, but there has been little study of microvascular flow properties, particularly in the hypertensive state. We have previously shown that skin blood flow in the rat had properties very similar to those in man. We used laser Doppler techniques to determine the effect of erythropoietin-induced polycythemia on skin blood flow in 12 Spontaneously Hypertensive Rats (SHR) as compared with 12 normotensive Wistar-Kyoto (WKY) rats. We contrasted flow values at the back and base of tail, nutritively (NUTR) perfused skin sites, with those at the plantar surface of the paw, a site with substantial arteriovenous anastomotic (AVA) perfusion. Erythropoietin treatment produced a substantially greater hematocrit response in the SHR rats, rising from 47 ± 1 to 64 ± 1, than in the WKY animals, who showed an increase from 46 ± 1 to 55 ± 1. Blood pressure was higher in the EPO-treated WKY and SHR rats: 157 ± 4 mm Hg as compared to 148 ± 2 mmg Hg in the WKY animals and 228 ± 4 mm Hg as compared to 201 ± 3 mm Hg, respectively (both p < 0.03). Erythropoietin treatment had very little effect on basal skin blood flow in either WKY or SHR rats. However, there was significantly lower heat-stimulated flow at the plantar surface of the paw in the EPO treated rats (WKY: 27.3 ± 1.9 ml/min/100 gm vs 35.5 ± 1.5 ml/min/100 gm in the untreated state; p < 0.02; SHR: 32.7 ± 2.6 ml/min/100 gm vs 45.4 ± 2.3 ml/min/100 gm in the untreated state; p < 0.01). In contrast, there was little difference at the back or tail. We conclude that erythropoietin-induced polycythemia affects flow in AVA rather than NUTR microvessels. Although raised vascular pressure has produced microvascular flow in our previous studies, the rise in pressure associated with high hematocrit appears to result from an increase in microvascular resistance, decreasing flow. Our study helps clarify clinical observations on the hemodynamic consequences of hematocrit elevation.

Role of prostaglandins and histamine in hyperemic response to superficial and deep gastric mucosal injury and H+ back-diffusion in cats.

This study was undertaken to examine the role of prostaglandins and histamine in the hyperemic response to gastric mucosal damage followed by H+ back-diffusion. Cat stomachs were exposed to 2 mol/liter NaCl for 10 min followed by luminal perfusion at pH 1. Hypertonic saline caused extensive (microscopic) damage to the surface epithelium, increased gastric mucosal blood flow, and increased release of histamine, PGE2, and 6-keto PGF1 alpha (prostacyclin) into portal venous blood. The effect of indomethacin and histamine blockers (H1 + H2) on the hyperemic response to acid back-diffusion was related to the depth of the mucosal injury and the region of the stomach. In the corpus, indomethacin enhanced mucosal injury. In areas with superficial damage, the hyperemia was inhibited by indomethacin and antihistamines and eliminated by the combination of both. In corpus areas with indomethacin-induced deep lesions, the blood flow was very high, and this hyperemia was partly inhibited by antihistamines. In the antrum the hyperemic response was reduced by antihistamines. Indomethacin increased the release of histamine into portal venous blood (baseline recordings) and reduced basal gastric mucosal blood flow.

Increased basal ganglia blood flow during memory activation in schizophrenia, relationship with auditory hallucinations

Increased basal ganglia blood flow during memory activation in schizophrenia, relationship with auditory hallucinations

Repeated Administration of SL 84.0418, a New Oral Antihyperglycaemic Agent

SL 84.0418 is an α2-adrenoceptor antagonist that has been proposed as an oral antihyperglycaemic agent for its ability to reduce glucose-evoked hyperglycaemia. The aim of the present study was to evaluate the pharmacological activity and safety of SL 84.0418 in healthy volunteers after repeated administrations. Ten male subjects (mean age 25 ± 3.1 years; mean body weight 77 ±11.7kg) took part in this open study. SL 84.0418 was administered as a single 10mg oral dose for 7 consecutive days, 1 hour after a standard breakfast. Pharmacological activity was assessed through plasma glucose and insulin concentrations, determined immediately before and 2 and 4 hours after administration on days 1, 3 and 7. The safety evaluation was based on: (a) daily physical examination (including bodyweight, blood pressure and heart rate); (b) basal and final routine blood tests as well as electrocardiographic findings; (c) adverse events spontaneously reported by the subjects. On days 1, 3 and 7, two hours after drug administration, a significant increase in plasma insulin levels associated with a significant (except for day 3) decrease in plasma glucose levels was observed. Plasma insulin and glucose levels returned to baseline levels 4 hours after administration. SL 84.0418 was well tolerated by all subjects with no clinically relevant adverse events. Physical examination, bodyweight and laboratory tests were unchanged during treatment. Cardiovascular parameters were not significantly modified, except for minor, asymptomatic variations in diastolic blood pressure in the supine position (78 ± 4.2 and 71 ± 9.6mm Hg on days 0 and 3, respectively) and in heart rate in the standing position on the first 2 days of treatment (74 ± 10.1, 83 ± 15.0 and 83 ± 12.0 beats/minute on days 0, 1 and 2, respectively). We conclude that SL 84.0418 is an orally active insulin-releasing agent that was well tolerated in healthy volunteers after administration of 10mg once daily for 7 days.

Basal cutaneous blood flow as a function of anatomical sites in smokers and non-smokers

Basal cutaneous blood flow as a function of anatomical sites in smokers and non-smokers

Effect of chronic ANG I-converting enzyme inhibition on aging processes. IV. Cerebral blood flow regulation

Age-related changes in systemic arterial blood pressure, basal cerebral blood flow (CBF), and CBF regulatory capacity were investigated in awake 6-, 12-, 24-, and 30-mo-old male Wistar (WAG/Rij) rats, one-half of which received the angiotensin I-converting enzyme inhibitor (ACEI) perindopril from 6 mo onward. There was no age-dependent change in mean arterial blood pressure, basal CBF, or cerebrovascular reactivity to hypercapnia, but the lower limit of CBF autoregulation rose from 70 mmHg at 6 and 12 mo to 90 mmHg in 24- and 30-mo-old animals. ACEI lowered mean arterial blood pressure but had no effect on basal CBF or on cerebrovascular reactivity to hypercapnia. ACEI shifted the lower limit of CBF autoregulation to a 20-mmHg-lower level in 12- and 24-mo animals but not in rats treated for 2 yr, i.e., from the ages of 6 to 30 mo. In conclusion, the main age-related change in CBF regulation was an increase in the lower limit of CBF autoregulation to a higher blood pressure level. Treatment with ACEI partially restored the lower limit of CBF autoregulation.

Effect of Local Inhibition of Nitric Oxide Synthesis on Forearm Blood Flow and Dorsal Hand Vein Size in Patients with Alcoholic Cirrhosis

1. Nitric oxide (NO) is a potent endogenous vasodilator and plays a role in the control of resting vascular tone. Patients with cirrhosis have a hyperdynamic circulation with reduced blood pressure and decreased peripheral resistance, and it is possible that increased production of NO due to induction of NO synthase may be involved in maintaining this vasodilatation. We have examined this possibility by studying the effects of local infusions of NG-monomethyl-L-arginine (an inhibitor of NO synthase) in the forearm arteriolar bed and the superficial dorsal hand veins of patients with alcoholic cirrhosis. 2. Drugs were either infused locally into the brachial artery and forearm blood flow was measured by venous occlusion plethysmography, or into a vein on the back of the hand and vein diameter was measured using a linear displacement technique. 3. Basal forearm blood flow was increased and vascular resistance was decreased in the patients with alcoholic cirrhosis compared with healthy control subjects. Noradrenaline and NG-monomethyl-L-arginine caused dose-dependent falls in forearm blood flow in both healthy control subjects and patients with cirrhosis. There was no significant difference in the responses to either noradrenaline or NG-monomethyl-L-arginine between the two groups. 4. In the superficial hand veins there was no change in vein size in response to NG-monomethyl-L-arginine infused alone, and venoconstriction to local infusion of noradrenaline was unaffected by co-infusion with NG-monomethyl-L-arginine. 5. Our results confirm that patients with alcoholic cirrhosis are vasodilated compared with healthy control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of neurally activated postjunctional adrenoceptors in cat forelimb vasculature.

We assessed the relative contribution of postjunctional alpha-adrenoceptor subtypes in neurally evoked vasoconstrictor responses in the forelimb of anesthetized cats. Preganglionic stimulation of the thoracic sympathetic nerve trunk produced frequency-related decreases in blood flow of the entire forelimb as measured by ultrasonic flowmetry as well as vasoconstriction in the digital cutaneous bed as measured by laser-Doppler flowmetry. Vasoconstrictor responses were not altered significantly by intravenous (i.v.) treatment with propranolol (1 mg/kg) or atropine (1 mg/kg). In the entire limb, prazosin, (3-100 micrograms/kg i.v.) was a more potent antagonist of neurally evoked responses as compared with rauwolscine. In contrast, rauwolscine (10-300 micrograms/kg i.v.) was a more effective antagonist in the cutaneous bed. Combined treatment with both prazosin and rauwolscine was far more effective than either antagonist given alone in blocking vasoconstriction regardless of the measurement site. Moreover, basal cutaneous blood flow was increased by rauwolscine but not by prazosin. These results suggest that both subtypes of postsynaptic alpha-adrenoceptors are activated by sympathetic nerve stimulation. In the cutaneous bed, alpha 2-adrenoceptors appear to predominate. In addition, cutaneous vascular tone also appears to be regulated by hormonal alpha 2-adrenoceptor activation in cats.

Effects of H1, H2 and H3 agonists on the neurogenic vasopressor response in the pithed rat

In pithed and vagotomized rats, the electrically induced vasopressor response was not affected by 2-(2-thiazolyl)ethylamine and dimaprit but was inhibited by Nα-methylhistamine (NαMH) in a thioperamidesensitive manner. NαMH did not affect the vasopressor response to exogenously added noradrenaline. NαMH produced a biphasic effect on basal diastolic blood pressure, i.e. a vasodepressor response (abolished by dimethindene plus ranitidine) and a subsequent vasopressor effect (counteracted by dimethindene or adrenalectomy). Basal heart rate was increased by NαMH (effect abolished by propranolol, dimethindene or adrenalectomy). In conclusion, presynaptic H3, but not H1 or H2, receptors are detectable in the resistance vessels of the rat. NαMH allows the characterization of another four histamine receptor-mediated effects, i.e vasodepressor effects mediated via H1 and H2 receptors and an increase in blood pressure and heart rate mediated via catecholamine-releasing H1, receptors in the adrenal medulla.

Identification of endothelial H1, vascular H2 and cardiac presynaptic H3 receptors in the pithed rat

In pithed and vagotomized rats the effects of the H3 receptor agonist R-(-)-alpha-methylhistamine, the H1 receptor agonist 2-(2-thiazolyl)ethylamine and the H2 receptor agonist dimaprit on basal diastolic blood pressure, basal heart rate and the electrically induced rise in heart rate were examined. Basal diastolic blood pressure was not altered by low, but increased by high doses of R-(-)-alpha-methylhistamine; the latter effect was not affected by selective H1, H2 or H3 receptor antagonists and by prazosin, but was attenuated by rauwolscine. Rauwolscine also unmasked a vasodepressor response to R-(-)-alpha-methylhistamine not affected by the H3 receptor antagonist thioperamide, but counteracted by the H1 receptor antagonist dimetindene or the H2 receptor antagonist ranitidine. The vasodepressor responses to 2-(2-thiazolyl)ethylamine and dimaprit were antagonized by dimetindene and ranitidine, respectively. The vasodepressor response to 2-(2-thiazolyl)ethylamine was not altered by indomethacin, but reduced by an inhibitor of endothelial nitric oxide synthase, N omega-nitro-L-arginine methyl ester (which, by itself, markedly increased blood pressure). Both drug tools did not alter the effect of dimaprit. Basal heart rate was not affected by 2-(2-thiazolyl)ethylamine (examined after administration of propranolol), dimaprit and R-(-)-alpha-methylhistamine. The electrically induced increase in heart rate (studied in animals which had received rauwolscine) was decreased by R-(-)-alpha-methylhistamine but not affected by 2-(2-thiazolyl)ethylamine and dimaprit. The effect of R-(-)-alpha-methylhistamine was abolished by thioperamide. R-(-)-alpha-methylhistamine did not influence the increase in heart rate produced by isoprenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Demonstration of the alpha-vasoconstriction-lowering effect of calcium in the pithed rat.

The mechanism by which calcium administration causes hypotension still remains to be explained. In this paper we have studied the alteration of the pressor effect caused by alpha 1- and alpha 2-adrenoceptor stimulation in the pithed rat after increasing the calcium plasma levels of the rats with an intraperitoneal administration of CaCl2. We compared the vasoconstrictor effect of the selective alpha 1-adrenoceptor agonist methoxamine (10-3,000 micrograms/kg) and the pressor effect of the selective alpha 2-adrenoceptor agonist B-HT 920 (1-1,000 micrograms/kg) in control rats (1.24 +/- 0.01 mmol/l ionic plasma calcium) and rats treated intraperitoneally with CaCl2 that had 1.89 +/- 0.04 or 3.03 +/- 0.11 mmol/l ionic plasma calcium. The pressor effect of methoxamine was noticeably less after both of the increases in ionic plasma calcium, and the pressor effect of B-HT 920 was also significantly reduced when the increase in calcium levels was more marked. We have also shown that administration of CaCl2 (8.8 mg Ca/100 g b.w. i.p.) did not alter the basal arterial blood pressure in the pitched rat; however, it caused an important decrease in blood pressure when administered 20 min after beginning an infusion of methoxamine (50 micrograms/min i.v.). The results indicated that the blood-pressure-lowering effect of acute calcium administration is at least in part due to peripheral mechanisms which include a reduction in the pressor responses caused by the alpha 1 and alpha 2 vascular receptor stimulation.

Glibenclamide decreases basal coronary blood flow in anesthetized dogs.

The effects of ATP-sensitive K+ channel blockade on coronary blood flow were studied in 13 anesthetized open-chest dogs. A specific ATP-sensitive K+ channel blocker, glibenclamide, was infused into the left circumflex coronary artery (LCx). Coronary blood flow of LCx and systolic segment shortening at the LCx area were measured. Intracoronary infusion of glibenclamide (0.5, 5, and 50 micrograms.kg-1.min-1) decreased coronary blood flow dose dependently. Glibenclamide at the dose of 50 micrograms.kg-1.min-1 decreased LCx coronary blood flow by 55 +/- 4% (P less than 0.01), which was accompanied by a decrease in percentage segment shortening at the LCx area (P less than 0.01) and ST elevation. When coronary blood flow was maintained at the baseline level by simultaneous infusion of sodium nitroprusside (1-3 micrograms/min ic) or pinacidil (0.3-0.6 mg/min ic), glibenclamide did not alter percentage segment shortening or produced ST elevation. The latter results suggest that glibenclamide decreased coronary blood flow, which secondarily induced myocardial ischemia and dysfunction. Our results suggest that ATP-sensitive K+ channels of coronary arteries are involved in maintaining the level of resting coronary blood flow under physiological conditions in anesthetized dogs.

Uterine prostaglandin production in ovine pregnancy: effects of angiotensin II and indomethacin.

The ovine and human uteroplacental vascular beds are more refractory to angiotensin II (ANG II)-induced vasoconstriction than the systemic vasculature. ANG II increases in vitro prostacyclin (PGI2) production by uterine but not omental arteries from pregnant sheep. Thus vasodilator prostaglandins may account for this difference in vascular responsiveness. We measured uterine and systemic eicosanoid production and hemodynamic responses in pregnant sheep before and during intravenous ANG II (1.15 and 11.5 micrograms/min). ANG II caused dose-related increases in arterial pressure and systemic and uterine vascular resistance (P less than 0.05). PGI2 metabolite (6-keto-PGF1 alpha) in the uterine vein rose from 166 +/- 70 (SE) to 223 +/- 114 and 631 +/- 323 pg/ml, respectively (P less than 0.05), and arterial levels increased from 67 +/- 24 to 145 +/- 78 and 312 +/- 173 pg/ml, respectively (P less than 0.05). Basal uterine venoarterial differences of 6-keto-PGF1 alpha were 99 +/- 43 pg/ml and increased during 11.5 micrograms ANG II/min to 295 +/- 181 pg/ml (P less than 0.05) but not during 1.15 micrograms/min (64 +/- 30 pg/ml). Responses were similar in gravid and nongravid uterine horns. Unilateral uterine prostaglandin inhibition with indomethacin did not alter basal uterine blood flow or systemic responses to ANG II (0.573-11.5 micrograms/min); however, ipsilateral uterine prostaglandin production fell and uterine vasoconstrictor responses increased (P less than 0.05). During ovine pregnancy ANG II increases uterine PGI2 production. PGI2 appears in part to attenuate ANG II-induced uterine vasoconstriction.

Renal failure increases gastric mucosal blood flow and acid secretion in rats: role of endothelium-derived nitric oxide.

Because of the contradictory findings in clinical studies, and the complete lack of animal studies, the purpose of this investigation was to characterize the changes in gastric mucosal blood flow (GMBF) and acid secretion in an animal model of chronic renal failure. Rats with chronic renal failure induced by partial kidney infarction had a significantly higher basal GMBF and lower gastric vascular resistance than control rats. The gastric acid secretory and mucosal hyperemic response to pentagastrin were markedly enhanced in renal failure rats. Because endothelial-derived nitric oxide (NO) is an endogenous vasodilator that regulates gastric vascular tone, we hypothesized that NO mediates the gastric hyperemia of renal failure rats. The administration of N omega-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of NO formation, produced a significantly greater decrease in GMBF in renal failure rats than in control rats, including a low dose inhibiting the basal hyperemia in renal failure rats but having no effect in control rats. It also attenuated pentagastrin-stimulated GMBF in both groups. In contrast, L-NAME produced a similar decrease in basal skeletal muscle blood flow in both renal failure and control rats. We conclude that in the renal failure rat 1) there is an increased basal GMBF and pentagastrin-stimulated acid output and GMBF, and 2) this gastric mucosal hyperemia is mediated by NO.

Inhibition of renal nitric oxide synthesis with NG-monomethyl-L-arginine and NG-nitro-L-arginine.

In barbiturate-anesthetized dogs, the effects of intrarenal infusion of the two selective inhibitors of nitric oxide synthesis, NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine (NO-Arg), were compared. Basal renal blood flow (RBF) was reduced by 15 +/- 2% after L-NMMA at 0.28 mumol/ml, by 20 +/- 3% after NO-Arg at 0.07 mumol/ml, and by 31 +/- 5% after NO-Arg at 0.56 mumol/ml. Endothelium-dependent vasodilation induced by intrarenal infusion of acetylcholine was unaltered after L-NMMA, reduced by 24 +/- 3% after NO-Arg at 0.07 mumol/ml, and reduced by 59 +/- 13% after NO-Arg at 0.56 mumol/ml. Endothelium-independent vasodilation induced by intrarenal infusion of atrial natriuretic factor was not reduced after L-NMMA and NO-Arg. This study shows that NO-Arg is more potent than L-NMMA in inhibiting basal renal nitric oxide synthesis. In contrast to L-NMMA, NO-Arg exerted an inhibitory effect on acetylcholine-induced renal vasodilation. Our findings indicate that one-third of the basal RBF and more than one-half of the increase in RBF during acetylcholine infusion are dependent on nitric oxide synthesis.

Pressor response to a postural change in cirrhosis: an experimental study in the CCl4-treated rat.

1. Systemic hypotension, blunted cardiovascular responsiveness to noradrenaline and an abnormal hypertensive pressor response to a postural change have been described in cirrhotic patients. 2. We have examined the role of blunted responsiveness in these abnormalities by studying basal arterial blood pressure and its response to a postural change (vertical head-up 90 degrees tilting) in conscious and pithed CCl4-treated (cirrhotic) rats, as well as assessing the pressor response to noradrenaline in vivo and the vascular contractile response to noradrenaline in vitro. 3. A diminished hypotensive response to a change in posture was found in pre-cirrhotic portal hypertensive rats, whereas an inverted hypertensive pressor response in the face of systemic hypotension occurred in the cirrhotic rats with portal hypertension. 4. The inverted pressor response was abolished in the pithed portal hypertensive cirrhotic rats. 5. The pressor response to noradrenaline in vivo in conscious cirrhotic rats and the vascular contractile responsiveness to noradrenaline in vitro were intact. 6. We conclude that blunted responsiveness to noradrenaline is not a contributory factor to the development of systemic hypotension or the inverted pressor response to a change in posture in cirrhosis.

Active and basal whole brain blood flow, oxygen and glucose metabolism in monkeys.

By definition, active cerebral metabolic rate for oxygen (ACMRO2) is the oxygen consumption associated with the generation of spontaneous electrical activity.1 The balance, or basal CMRO2, is presumably, the oxygen consumed to maintain neuronal viability through ion pumping and reparative and synthetic metabolic pathways.2 This concept evolved out of interest in the mechanism of action of anesthetics and the hypothesis that the effect of anesthetics on cerebral metabolism is secondary to a direct effect on cerebral function.3

Ouabain and responses to endothelium-dependent vasodilators in the human forearm.

Ouabain inhibits endothelium-dependent vascular relaxation in vitro, but has not been studied in this regard in vivo. We have therefore measured blood flow responses to carbachol, bradykinin and sodium nitroprusside (endothelium-dependent and endothelium-independent vasodilators) infused into the brachial artery with and without co-infusion of ouabain (2 micrograms min-1). Six healthy male volunteers were each studied on two occasions. Ouabain reduced basal forearm blood flow, by 18.0 +/- 4.1% (mean +/- s.e. mean, 2P less than 0.05), but had no significant effect on responses to any of the three vasodilators. These results indicate that effects of ouabain on endothelium-dependent relaxation in vitro must be interpreted with caution.