Thermogenic response to adrenaline during restricted blood flow in the forearm.

To elucidate the underlying mechanism behind the thermogenic effect of adrenaline in human skeletal muscle, nine healthy subjects were studied during intravenous infusion of adrenaline. Restriction of blood flow to one forearm was obtained by external compression of the brachial artery, to separate a direct metabolic effect of adrenaline from an effect dependent on increased blood flow. The other arm served as the control arm. In the control arm, the forearm blood flow increased 4.7-fold (from 2.0 +/- 0.3 to 9.3 +/- 1.5 mL 100 g(-1) min(-1), P < 0.001) during the adrenaline infusion. Adrenaline significantly increased forearm oxygen consumption (from 4.7 +/- 2.1 to 7.0 +/- 3.6 micromol 100 g(-1) min(-1), P < 0.025). In the arm with restricted blood flow, the forearm blood flow increased 2.9-fold (from 1.6 +/- 0.3 to 4.6 +/- 0.8 mL 100 g(-1) min(-1), P < 0.002) but the forearm oxygen consumption did not increase (baseline period: 5.6 +/- 2.3 micromol 100 g(-1) min(-1), adrenaline period: 6.1 +/- 2.1 micromol 100 g(-1) min(-1), P = 0.54). The experimental design and the difficulties in interpretation of the result are discussed. The results give evidence for the hypothesis that the vascular system plays a key role in the thermogenic effect of adrenaline in skeletal muscle in vivo.     

Global cerebral blood flow during infusion of adenosine in humans: assessment by magnetic resonance imaging and positron emission tomography

Adenosine, an endogenous vasodilator, induces a cerebral vasodilation at hypotensive infusion rates in anaesthetized humans. At lower doses (< 100 μg kg^?1 min^?1), adenosine has shown to have an analgesic effect. This study was undertaken to investigate whether a low dose, causing tolerable symptoms of peripheral vasodilation affects the global cerebral blood flow (CBF). In nine healthy volunteers CBF measurements were made using axial magnetic resonance (MR) phase images of the internal carotid and vertebral arteries at the level of C2–3. Quantitative assessment of CBF was also obtained with positron emission tomography (PET) technique, using intravenous bolus []> ¹⁵O]butanol as tracer in four of the subject at another occasion. During normoventilation (5.4 ± 0.2 kPa, mean ± s.e.m.), the cerebral blood flow measured by magnetic resonance imaging technique, as the sum of the flows in both carotid and vertebral arteries, was 863 ± 66 mL min^?1, equivalent to about 64 ± 5 mL 100 g^?1 min^?1. The cerebral blood flow measured by positron emmission tomography technique, was 59 ± 4 mL 100 g^?1 min^?1. All subjects had a normal CO₂ reactivity. When adenosine was infused (84 ± 7 μg kg^?1 min^?1) the cerebral blood flow, measured by magnetic resonance imaging was 60 ± 5 mL 100 g^?1 min^?1. The end tidal CO₂ level was slightly lower (0.2 ± 0.1 kPa) during adenosine infusion than during normoventilation. In the subgroup there was no difference in cerebral blood flow as measured by magnetic resonance imaging or positron emission tomography. In conclusion, adenosine infusion at tolerable doses in healthy volunteers does not affect global cerebral blood flow in unanaesthetized humans.     

The cortical and medullary blood flow at different levels of renal nerve activity

The effect of (1) renal denervation and (2) stimulation of the renal nerve on the regional renal blood flow were determined by the Rb uptake method. Under control conditions the total renal blood flow was 3.64±0.09 ml·min^-1·g^-1 tissue increasing significantly (p<0.02) to 4.39±0.28 ml·min^-1·g^-1 after denervation. Upon stimulation of the peripheral portions of the sectioned renal nerves the blood flow decreased almost linearly with the frequency of stimulation reaching 0.99±0.24 ml·min^-1·g^-1 at 10 Hz. Utilizing the relation between blood flow and stimulation frequency the control blood flow correspond to a spontaneous activity of 1.5 Hz. As expected the cortical blood flow responded in the same way as for the total renal blood flow. In the renal medulla denervation gave a much more pronounced response where e.g. the inner medullary flow increased from 0.88±0.09 to 1.30±0.16 ml·min^-1·g^-1, i.e. a 50% increase (p<0.05). Stimulation with 2 Hz produced a steep fall in the blood flow, whereafter it decreased linearly with the stimulation frequency reaching 0.11 ml·min^-1·g^-1 at 10 Hz stimulation. This demonstrates again that the renal medulla is sensitive to renal nerve activity primarily in the low level range. It should be remarked, however, that the 86-Rb uptake method reflects the effective blood flow, which might differ from the blood flow in absolute terms. It is concluded that the renal nerve activity influences the blood flow of all regions of the kidney within the entire range 0–10 Hz. The renal medullary blood flow is affected presumably to a greater extent in the low level range around the basal tone. The sympathetic nerves might then also be important with respect to the urine concentration mechanism.     

Effect of anaesthetizing the region of the paraventricular hypothalamic nuclei on energy metabolism during exercise in the rat

The ventromedial and posterior hypothalamic nuclei are known to influence glucoregulation during exercise. The extensive projections of the paraventricular hypothalamic nucleus (PVN) to the sympathetic nervous system suggest that the PVN also may be involved in glucoregulation during exercise. The region of the PVN was anaesthetized with bupivacaine before running (26 m min^-1) or continued rest, via previously implanted bilateral brain cannulas aimed at the dorsal aspect of the PVN. Control rats were treated identically to PVN-anaesthetized rats, but were not infused. Blood, for determination of plasma concentrations of metabolites and hormones, was drawn from a tail artery, and ³H-glucose was infused in a tail vein for glucose turnover determinations. At rest, no significant changes in plasma concentrations of metabolites or hormones were induced by anaesthesia of the region of the PVN. During exercise, glucose production and utilization and plasma concentrations of glucose, lactate, glycerol, noradrenaline, adrenaline, corticosterone, and glucagon increased (P < 0.02) and plasma insulin decreased (P < 0.02) in all rats. However, initially in exercise, adrenaline (4.3 ±0.8 vs. 7.9 ± 1.0 nmol 1^-1 in controls, P < 0.05, t= 6 min) and later corticosterone levels (1.37 ± 0.06 vs. 1.69 ± 0.10 nmol 1^-1 in controls, P < 0.05, t = 20 min) were attenuated by PVN anaesthesia. Initially during exercise, glucose utilization was higher and plasma glucose lower in PVN-anaesthetized rats compared to controls (16.6 ± 0.8 vs. 12.7 ± 0.6 μmol min^-1 100 g^-1 and 7.1 ± 0.2 vs. 8.1 ± 0.2 mmol 1^-1, respectively. P < 0.05, t= 6 min) and exercise-induced liver glycogen breakdown was only significant in the controls. In conclusion, the region of the PVN does not influence glucoregulation at rest, but affects glucoregulation during exercise, by stimulating adrenaline and corticosterone secretion during exercise.     

Influence of adenosine on the vascular responses to sympathetic nerve stimulation in the canine subcutaneous adipose tissue

Adenosine appears to regulate resting blood flow in canine subcutaneous adipose tissue. Sympathetic nerve stimulation has been shown to enhance the adenosine production in this tissue. This study therefore tested the possibility that adenosine may influence the vascular responses to sympathetic nerve stimulation. Intraarterial infusion of adenosine (5–20 μM in arterial blood) increased the resting vascular conductance (from 0.048 ± 0.007 to 0.095 ± 0.013 ml ± min^-1100 g^-1± mmHg^-1) and the percental reduction in vascular conductance due to sympathetic nerve stimulation (4 Hz) by 34 per cent (p<0.05) and to i. a.noradrenaline by 27 per cent (p<0.05). The vasodilator response due to nerve stimulation after α-blockade was reduced by adenosine. Dipyridamole (0.5–1.5 μM) + EHNA (3–10 μM), which increases plasma adenosine levels, had similar effects to adenosine, while theophylline (30–80 μM) decreased the vasoconstrictor response. The vasoconstrictor escape was enhanced by EHNA alone and in combination with dipyridamole, but was reduced by theophylline. On the other hand, the poststimulatory hyperemia was unaffected by adenosine, dipyridamole and EHNA, and theophylline. The results show that adenosine does not reduce the magnitude of the initial vasoconstrictor response in proportion to the increase in resting blood flow. The autoregulatory escape in adipose tissue during nerve stimulation appears to be mediated both by adenosine and by noradrenaline acting on β-adrenoceptors. Poststimulatory hyperemia does not seem to be greatly influenced by exogenous or endogenous adenosine     

Exogenous endothelin-1 causes peripheral insulin resistance in healthy humans

In states of insulin resistance, increased plasma levels of endothelin-1 and a disturbed vascular reactivity have been reported. In order to investigate the effects of endothelin-1 on peripheral insulin sensitivity and the vasoactive interactions between insulin and endothelin-1, six healthy subjects were studied on two different occasions with the euglycaemic hyperinsulinaemic clamp technique combined with an intravenous infusion of either endothelin-1 (4 pmol kg^?1 min^?1) or 0.9% sodium chloride. During the endothelin-1 infusion, arterial plasma endothelin-1 levels rose 10-fold. The endothelin-1 infusion reduced insulin sensitivity as demonstrated by a 31 ± 7% decrease in whole-body glucose uptake (P < 0.05) and a 26 ± 11% fall in leg glucose uptake (P < 0.05) compared with the control protocol. During the state of hyperinsulinaemia, exogenous endothelin-1 increased mean arterial blood pressure by 8 ± 1% (P < 0.05) and decreased splanchnic and renal blood flow by 30 ± 6% (P < 0.001) and 20 ± 4% (P < 0.001), respectively. However, the endothelin-1 infusion did not lower skeletal muscle blood flow measured as leg and forearm blood flow. In summary, exogenous endothelin-1 induced insulin resistance in healthy humans by reducing insulin-dependent glucose uptake in skeletal muscle without decreasing skeletal muscle blood flow. Furthermore, endothelin-1 also preserved its vasoactive potency in the presence of hyperinsulinaemia.     

Blood flow in the rabbit tenuissimus muscle Influence of preparative procedures for intravital microscopic observation

LINDBOM, L., TUMA, R. F. & ARFORS, K.-E.: Blood flow in the rabbit tenuissimus muscle: Influence of preparative procedures for intravital microscopic observation. Acta Physiol Scand 1982, 114 :121–127. Received 21 April 1981. ISSN 0001–6772. Department of Experimental Medicine, Pharmacia AB, Uppsala, Sweden. The tenuissimus muscle in the rabbit and the cat is a suitable tissue for intravital microscopic investigation of skeletal muscle blood flow. In this study the influence of surgical procedures necessary for direct microscopic observation on the physiological state of the rabbit tenuissimus muscle was assessed by means of blood flow measurements. Mean resting blood flow was 2.8±0.8 (mean ± S.D.) ml. min^-1. 100 g^-1 in the left tenuissimus muscle when prepared for microscopic observation as determined by the radioactive microsphere method. This value was not significantly different from that in the intact unexposed muscle in the contralateral leg, 3.3 ±1.1 ml. min^-1. 100 g^-1. Exposure of the muscle to atmospheric oxygen tension resulted in a reduction of blood flow to 0.7±0.4 ml. min^-l. 100g^-l, suggesting that local metabolic control mechanisms were active. The normal range of vascular control seemed to be maintained, as demonstrated by an increase in blood flow to 64.2± 18.8 ml. min-¹. 100 g^-l during “maximal” vasodilation induced by topical application of PGE₁. The tenuissimus muscle showed a marked sensitivity to mechanical stimulation. Slight stretching of the muscle, similar to what may occur during surgical preparation, resulted in an increase in blood flow to 17.5±5.7 ml. min^-1. 100 g^-1. Flow values calculated from data obtained by direct microscopic measurements in the tenuissimus muscle agreed well with those obtained by the microsphere method.     

Physiological and morphological effects of perfusing isolated rat kidneys with hyperosmolal mannitol solutions

Recently, we were able to modify the glomerular charge barrier using perfusates with low and normal ionic strengths keeping the osmolality unchanged. The concentration of fixed charges was reversibly reduced from 35 to 12 mEq L^–1 as the solution with low content of NaCl was introduced with no apparent effect on the size selectivity. It can be argued however, that the mannitol used for maintenance of osmolality may induce changes in glomerular permeability per se. To explore this possibility, isolated kidneys were perfused at 8° with hyperosmolal mannitol solutions (560 mOsm) and compared with those perfused with standard albumin solutions (295 mOsm). The vascular resistance (PRU₁₀₀) fell from 0.14 ± 0.01 to 0.11 ± 0.01 mmHg min 100 g mL^–1 as the mannitol solution was introduced (P < 0.001). As the blood pressure should remain unchanged, the flow was increased from 8 to 11 mL min^–1. The glomerular filtration rate (GFR) increased by 50% from 320 ± 40 to 490 ± 20 μL min^?1 g^–1 (P < 0.001). Despite these changes in haemodynamical parameters, there was no significant change in the fractional clearance for albumin. Kidneys perfused with the mannitol solution showed well-preserved histology, while there was a conspicuous collapse of the cortical tissue and signs of tubular epithelial swelling with the standard perfusate. Moreover, all glomeruli were perfused in the mannitol group, as revealed by fluorescence of FITC dextran, while the distribution was uneven in the control kidneys. We conclude that perfusion of isolated kidneys with a hyperosmolal mannitol solution increased GFR by increasing the number of functionally active nephrons with no apparent effect on the glomerular barrier, a pattern differing from alteration of ionic strength.     

Effects of alpha2-adrenoceptor blockade and thyrotropin-releasing hormone (TRH) on the cardiovascular system in the rabbit

The effects of two different doses of thyrotropin-releasing hormone on regional blood flows were studied in urethane-anaesthetized rabbits pretreated with the α₂ adrenergic antagonists yohimbine and idazoxan. The effects of yohimbine were also studied using unanaesthetized rabbits. Blood flow measurements were performed using the tracer microsphere method. Thyrotropin-releasing hormone was injected i. v. at a dose of either 0.1 mg kg^-1 or 2.0 mg kg^-1. Yohimbine and idazoxan did not modify the effect of thyrotropin-releasing hormone on mean arterial blood pressure. In the anaesthetized animals, blockade of the α₂ adrenoceptors resulted in a vasoconstriction in several peripheral organs and the vasoconstriction increased after thyrotropin-releasing hormone administration. Pretreatment with yohimbine reduced total cerebral blood flow moderately and in such animals thyrotropin-releasing hormone elicited only minor cerebral blood flow effects. Pretreatment with idazoxan did not reduce the total cerebral blood flow and in such animals it increased from 53± 1 to 75±4 g min^-1 100 g^-1 (P < 0.01) after the administration of the lower dose of thyrotropin-releasing hormone and from 64±5 to 112±17 g min^-1 100 g^-1 (P < 0.01) after the higher dose. In the conscious animals, yohimbine caused an increase in mean arterial blood pressure and heart rate. Vascular resistance increased in several organs. The cerebral blood flow decreased in white matter (P <0.05) and the caudate nucleus (P < 0.05). The results indicate that there is a yohimbine-sensitive mechanism involved in the cerebrovasodilating effect of thyrotropin-releasing hormone in anaesthetized rabbits. There is also an activation of the sympathetic nervous system by thyrotropin-releasing hormone which results in increased vascular resistance and mean arterial blood pressure. Its effect on the vascular resistance may be enhanced by α₂ adrenoceptor blockade. In conscious animals, there seems to be a yohimbine-sensitive mechanism involved in the control of cerebral blood flow.     

Natriuresis in conscious dogs caused by increased carotid [Na+] during angiotensin II and aldosterone blockade

The renal response to a selective increase in the Na⁺ concentration of the blood perfusing the central nervous system was investigated in conscious dogs treated with the converting enzyme inhibitor enalaprilat and the aldosterone antagonist canrenoate. In split-infusion experiments the plasma [Na⁺] of carotid blood was increased (approx. 6 mM) by bilateral infusion of hypertonic NaCl. Concomitantly distilled water was infused into the v. cava making the sum of the infusions isotonic. In control experiments isotonic saline was infused at identical rates into all three catheters. Na⁺ excretion increased markedly in both series, 103 ± 14 to 678± 84 μmol min^-1 during split-infusion and 90 ± 14 to 496 ± 74 μmol min^-1 during the isotonic volume expansion. Peak rate of excretion, peak fractional sodium excretion, and cumulative sodium excretion were all significantly higher (P < 0.05) during split-infusion than during control experiments. Plasma vasopressin increased only during split-infusion (0.68 ± 0.11 to 2.4 ± 0.8 pg ml^-1) while the increases in plasma atrial natriuretic peptide were similar in the two series. Urinary excretion of urodilatin (ANP95-126) increased significantly more during split-infusion (46 ±11 to 152 ±28 fmol min^-1) than during the isotonic volume expansion (45 ± 14 to 84 ± 16 fmol min^-1) (P < 0.05). It is concluded that the natriuretic mechanisms activated by a selective increase in the Na⁺ concentration of carotid blood and associated with increased excretion of urodilatin cannot be eliminated by blockade of the renin-angiotensin-aldosterone system.     

High afterload during 10 min of regional ischaemia affects diastolic creep but not systolic function in reperfused (stunned) myocardium

The effect of afterload during regional ischaemia on myocardial stunning was studied in 15 pentobarbital anaesthetized cats. 10 min occlusion of the left anterior descending artery (LAD) was followed by 60 min of reperfusion. Afterload was decreased by intravenous infusion of nitroglycerine 3–8 μg kg^-1 min^-1 in group I (n=8); left ventricular peak systolic pressure (LVSP) 84±4 mmHg (mean±SEM) during coronary artery occlusion. In group II (n=7) LVSP was increased to 188±10 mmHg by inflating an intraaortic balloon during coronary artery occlusion. Regional function in the LAD perfused region was evaluated by cross-oriented sonomicrometry. Myocardial tissue blood flow was evaluated by radio-labelled microspheres. Afterload alterations did not affect regional systolic shortening (10.8±2.0% vs. 11.0±1.5% in group I and II, respectively, after 60 min of reperfusion). However, increased end-diastolic dimensions (diastolic creep) in both the circumferential and longitudinal segments were markedly more pronounced in the high afterload group (group II). Also important, the markedly increased myocardial tissue blood flow during reperfusion in group II as compared with group I (2.30±0.18 vs.  1.34±0.08 mL min^-1 g^-1 and 2.58±0.23 vs. 1.49±0.07 mL min^-1 g^-1 in subepicardial and subendocardial layers in the LAD perfused region) suggests that increased diastolic creep increased metabolic demands. This study indicates that passive stretching of the ischaemic area during coronary artery occlusion is an important mechanism behind diastolic creep.     

Reduced platelet glutathione peroxidase activity and serum selenium concentration in atopic asthmatic patients

Background Asthmatic inflammation results in increased oxygen free radical generation and assessment of the activity of the selenitim (Se) dependent anti-oxidant enzyme, glutathione peroxidase (GSH-Px) in asthma may therefore be important. Objective To test the hypothesis that reduced GSH-Px activity and Se intake contribute to asthmatic infiammation, platelet and whole blood GSH-Px activities and serum and whole blood Se concentrations were measured and compared in atopic and non-atopic asthmatic patients and non-asthmatic control subjects. Methods GSH-Px activities of whole blood and isolated platelets were assessed in 41 asthmatic patients (33 atopic) and 41 age- and sex-matched non-asthmatic sttbjects (15 atopic) by spectrophotometric assay based oti the oxidation of NADPH. Se concentrations were determined by semi-automated fluorimetric assay. Results Mean (± sd) platelet GSH-Px activity was lower in asthmatic (89.5 ± 45.7 μmol NADPH oxidized min^?1 g^?1 of protein) than in non-asthmatic subjects (109,9 ± 41.9; P= 0.038) and in atopic (89.7 ± 45.1, n = 48) compared with non-atopie subiects (113.7 ± 40.9, n= 34: P= 0.016). Mean whole blood GSH-Px activity was also lower in atopic (12.2 ± 5.2 μmol NADPH oxidized min^?1 g^?1 of Hb) than in non-atopic subjects (14.5 ± 4.2; P= 0.038). In non-asthmatic subjects, the mean whole blood GSH-Px activity was lower in men (9.9 ± 3.5) than in women (14.5 ± 3.7; P = 0.0004) and was positively correlated with age (r= 0.51; P = 0.0006). Mean serum Se was lower in asthmatic (1.07 ± 0.12 μmol/L) than in non-asthmatic subjects (1.16 ± 0.31; P = 0.036), Using multiple linear regression, asthma was an independent predictor of decreased platelet GSH-Px after gender, age and serum Se were taken into account (P = 0.048) while atopy was a significant predictor of low whole blood GSH-Px independent of asthma, gender, age and whole blood Se (P = 0.033). Conclusions In addition to Se status, atopy, gender and uge all appear to influence GSH-Px activity, although the relative importance of these factors may difler in asthmatic and non-asthmatic populations. It seems likely that the reduced activity of this enzyme in platelets und hiood may reflect mechanisms associated with the pathogenesis and severity of asthma.     

Effects of indomethacin on regional blood flow in conscious rabbits—a microsphere study

In an attempt to reveal the importance of prostaglandins in the control of regional blood flow 20 mg/kg b.wt. indomethacin was given i.v. in conscious resting rabbits. Regional blood flow determinations were made before and 20 min after the injection using the labelled microsphere technique. The blood flow in the stomach wall was reduced by 0.75 ± 0.17 g·min^-1·g^-1 from a level of 1.64 ± 0.24 g·min^-1·g^-1. In jejunum the corresponding figures were 0.44 ± 0.12 and 1.26 ± 0.17 and in the brain 0.29 ± 0.10 and 1.24 ± 0.10. The blood flow in the liver via the hepatic artery increased by 0.20 ± 0.02 g·min^-1·g^-1 from a level of 0.13 ± 0.02 g·min^-1·g^-1. In the retina there was a reduction in blood flow by 2.75 ± 1.03 mg·min^-1 from a starting level of 15.1 ± 2.3 mg·min^-1. In a number of other tissues investigated there were no significant effects of the drug. The results suggest that under resting conditions prostaglandins play a role in the control of blood flow in the gastrointestinal tract, the brain and the retina—tissues which are likely to be rather active under such conditions.     

Cardiovascular and endocrine responses to haemorrhage in the pig

Heart rate (HR), mean arterial pressure (MAP), indices of sympathetic and parasympathetic activity (plasma concentrations of adrenaline, noradrenaline and pancreatic polypeptide, PP), vasopressin (VP) and aldosterone (ALDO) were measured in six pigs during continuous bleeding resulting in hypovolaemic shock, from which five survived. Three stages of haemorrhage could be defined. Stage I. Resting MAP was 85 ± 6 mmHg and increased to 96 ± 5 mmHg with a blood loss of 275 (range 250–300) (10 (9–12)% of the estimated blood volume) concomitant with an increase in HR from 105 ± 5 to 113 ± 6 beats min^-1 (P < 0.05). Stage II. After a blood loss of 375 (300–500) ml (15 (13–16)%) MAP fell to 62 ± 9 mmHg and HR to 95 ± 5 beats min^-1 (P < 0.05). Stage III. A blood loss of 1113 (825–1450) ml (44 (30–52)%) resulted in a MAP of 50 ± 4 mmHg and an increase in HR to 206 ± 3 beats min^-1 (P < 0.05). Adrenaline increased from 0.3 ± 0.1 to 0.8 ± 0.3 (stage II) and 3.6 ± 1.1 nmol l^-1 (stage III) (P < 0.05); noradrenaline from 0.4 ± 0.1 to 1.5 ± 0.4 (stage II) and 5.9 ± 1.7 nmol l^-1 (stage III) (P < 0.05); PP from 6.2 ± 1.6 to 13.3 ± 2.3 (stage II) and 20.9 ± 7.8 pmol l^-1 (stage III) (P < 0.05). VP changed only marginally, but ALDO increased from 496 ± 54 to 623 ± 76 pmol l^-1 (stage III) (P < 0.05). The results suggest that a high HR and intense sympathetic activity is seen during severe haemorrhage in the pig while vagal slowing of the heart and moderate hypotension are prominent when bleeding amounts to approximately 15% of the estimated blood volume.     

Influence of intravenously administered catecholamines on cerebral oxygen consumption and blood flow in the rat

In order to study effects of catecholamines on cerebral oxygen consumption (CMRo₂) and blood flow (CBF), rats maintained on 75 % N₂O and 25 % O₂, were infused i.v. with noradrenaline (2, 5, or 8 μpg. kg^-1. min^-1) or adrenaline (2 or 8, μg. kg^-1.min^-1) for 10 min before CBF and CMR_oz were measured. In about 50% of animals infused with 2–8, μg. kg^-1 min^-1 of noradrenaline, CMRo_z (and CBF) rose. However, there was no dose-dependent response, and CMRo₂, did not exceed 150% of control. The effects of noradrenaline in a dose of 5 μg. kg^-l. min^-1 on CMRo₂, and CBF were blocked by propranolol (2.5μg.kg^-1). In animals infused with adrenaline (8 μg.kg^-1.min^-1) CMRo₂, was doubled and, in many, CBF rose 4- to 6-fold. It is concluded that, when given in sufficient amounts, catecholamines have pronounced effects on cerebral metabolism and blood flow, the effects of adrenaline on CMRo₂, and CBF resembling those observed in status epilepticus.     

Acute renal denervation causes time-dependent resetting of the tubuloglomerular feedback mechanism

Renal effects of acute renal denervation (DNX) were studied in anaesthetized rats. In a first series, whole kidney clearance measurements were made 120 and 240 min after unilateral DNX. At 240 min, urine production was 3.59±0.87 μL min^-1 in control kidneys and 7.74±1.97 μL min^-1 in denervated kidneys. The corresponding values for sodium excretion were 0.56±0.17 and 1.41±0.34 μmol min^-1, potassium excretion 0.48±0.08 and 0.97±0.37 μmol min^-1 and glomerular filtration rate (GFR) 0.83±0.08 and 1.05±0.16 mL min^-1, respectively. In a second series, tubuloglomerular feedback (TGF) characteristics were determined with the stop-flow pressure (P_sf) technique. With increasing time, the sensitivity of the TGF mechanism diminished in denervated rats, as indicated by an increased turning point (TP). TP was significantly increased 2 h after DNX from 19.1±1.13 in control to 25.9±1.10 nL min^-1. TP was further increased 4 h after DNX to 37.3±3.12 nL min^-1. However, the maximal TGF response to increased flow in the late proximal tubule was not altered. But, P_st was significantly higher in DNX rats than in the controls (47.4±1.01 vs. 43.0±1.53 mmHg) in spite of a lower blood pressure (107±2.9 vs. 119±2.2 mmHg). We conclude that intact renal nerves are essential for the setting of the TGF sensitivity and hence the regulation of GFR     

Effects of bradykinin and papaverine on renal autoregulation and renin release in the anaesthetized dog

The present study on six anaesthetized dogs investigates the influences of two different vasodilators, bradykinin and papaverine, on the relationship between autoregulation of renal blood flow and glomerular filtration rate, sodium excretion and renin release. At control conditions renal blood flow and glomerular filtration rate was autoregulated to the same levels of renal arterial pressure, 55 ± 3 and 58 ± 3 mmHg, respectively. Renin release increased from 0.3±0.1 to 22±4 μg AI min^-1, and sodium excretion decreased from 99 +29 to 4.6 ± 3.3 μmol min^-1 when renal arterial pressure was reduced from 122±6 to 44±2 mmHg. Infusion of bradykinin (50 ng kg^-1 min^-1) increased renal blood flow by 50% at control blood pressure without changing glomerular filtration rate, and both renal blood flow and glomerular filtration rate autoregulated to the same pressure levels as during control. Sodium excretion increased threefold at control renal arterial pressure, but was unchanged at low renal arterial pressure. Bradykinin did not change renin release neither at control nor low renal arterial pressure. Papaverine infusion at a rate of 4 mg min^-1 increased renal blood flow 50% without changing glomerular filtration rate. The lower pressure limits of renal blood flow and glomerular filtration rate autoregulation were increased to 94±6 and 93±6 mmHg, respectively. Sodium excretion increased sixfold at control renal arterial pressure and was still as high as the initial control values at low renal arterial pressure (97±27 μmol min^-1) accompanied by only a small increase in renin release (1.4±0.3 to 6±2 μg AI min^-1). We conclude that bradykinin does not influence autoregulatory pressure limits of renal blood flow and glomerular filtration rate nor the accompanying increase in renin release during reductions in renal arterial pressure. Papaverine on the other hand maintains high sodium chloride delivery to macula densa at low renal arterial ressure, suppressing renin release and impairing autoregulation through effects on the tubulo-glomerular feedback mechanism.     

Capillary diffusion capacity for Cr-EDTA and cyanocobalamine in spontaneously beating rat hearts

In order to obtain a functional estimate of the diffusional capacity of the myocardial capillary bed, the permeability surface area product (PS) for Cr-EDTA (mol. wt = 341) and cyanocobalamine (vitamin B₁₂, mol. wt = 135) was determined in spontaneously beating Langendorff-perfused rat hearts over a wide range of coronary flow rates (700–3000 ml min-¹ 100 g-^l). PS was determined by a single injection, colorimetric indicator dilution technique, allowing multiple, rapid and accurate determinations to be made in the same heart. During maximal vasodilation with nitroprusside Na PS averaged 535 ± 33 and 220 ± 22 ml min^-1 100 g^-1 for Cr-EDTA and vitamin B₁₂ respectively at the highest flow (2917 ±74 ml min^-1 100 g^-1). The vasculature of the heart was found to be highly hererogeneous, since PS increased with flow and there were marked variations of extraction over transit times. A functional estimate of ‘equivalent pore radius’ was obtained from the ratio PS_Cr.EDTA/PS_B12, which was 2.61 ± 0.15 demonstratiag a marked restriction to diffusion corresponding to a pore radius of 51 (41–75) Å. This value is similar to that from skeletal muscle determined by the same method while PS-values are 40–45 times higher in the heart (Haraldsson & Rippe 1986). Taken together with morphological estimations of capillary surface area and endothelial path depth, these data indicate a 3-fold increase in the density of pores available for diffusion in the myocardium, compared to skeletal muscle.     

The energetics of the quiescent heart muscle: high potassium cardioplegic solution and the influence of calcium and hypoxia on the rat heart

Heart basal metabolism has been classically studied as the energy expenditure of those processes unrelated to mechanical activity and often measured by rendering the heart inactive using cardioplegic solutions (usually by increasing extracellular K concentration ([K]_e). In arterially perfused rat heart (at 25 °C), raising [K]e from 7 to 25 mM at a constant extracellular Ca concentration ([Ca]_e) (0.5 mM ), induced an increase in resting heat production (Hr) from 4.1 ± 0.3 to 5.1 ± 0.3 mol. wt g^?1. Under 25 mM K additional increase in [Ca]_e further increased Hr to 6.0 ± 0.4, 7.0 ± 0.4 and 8.3 ± 0.9 mol. wt g^?1 for 1, 2 and 4 mM Ca, respectively. While under 7 mM K perfusion Hr was not affected by 4 μM verapamil, under 25 mM K and 2 mM Ca 0.4 μM verapamil induced a decrease in Hr (?1.6 ± 0.2 mol. wt g^?1, n = 5, P < 0.001). Caffeine increased Hr under 0.5 mM Ca and 7 mM K perfusion (+0.32 ± 0.06 and +1.19 ± 0.25 mol. wt g^?1 for 1 and 5 mM caffeine respectively), but under 25 mM K conditions Hr was not affected by caffeine 2 mM . Severe hypoxia decreased Hr under both 7 and 25 mM K (3.7 ± 0.5 to 2.7 ± 0.4 mol. wt g^?1 and 7.0 ± 0.4 to 2.2 ± 0.5 mol. wt g^?1, respectively) suggesting that the increased Hr associated with the verapamil sensitive fraction of heat released is associated to a mitochondrial mechanism. Therefore, the use of high [K]_e overestimates basal values by increasing a verapamil sensitive fraction of the energy released. In addition, high [K]_e modifies a caffeine sensitive energy component probably due to a depletion of caffeine-dependent Ca stores.     

Skeletal muscle perfusion in electrically induced dynamic exercise in humans

Leg blood flow, blood pressure and metabolic responses were evaluated in six men during incremental one-legged dynamic knee extension exercise tests (no load exercise - 40 W); one performed with voluntary contractions (VOL) and one with electrically induced contractions (EMS). Pulmonary oxygen uptake was the same in both exercise modes, but the ventilatory coefficient was 2–5 L per L O₂ higher in EMS than VOL (P < 0.05). Heart rate and mean arterial pressure were slightly higher with EMS than VOL at all exercise intensities reaching 138 (EMS) and 126 bpm (VOL), as well as 148 (EMS) and 137 mmHg (VOL) at 40 W, respectively (P < 0.05). Leg blood flow, oxygen uptake and conductance were similar in the two exercise modes. At 40 W, mean muscle blood flow was close to 200 (range: 165–220) mL 100 g^-1 min^-1, mean peak muscle oxygen uptake reached 230 mL kg^-1 min^-1, and mean conductance became as high as around 45 mL min^-1 mmHg^-1, and normalized for muscle size and arterial pressure it approached 100 mL min^-1 100 g^-1 100 mmHg^-1. Lactate and ammonia efflux from the leg were higher with EMS than with VOL and the difference became larger with increasing exercise intensity (P < 0.05). Muscle glucose uptake was the same in each exercise mode. Femoral venous K⁺ concentration increased with exercise intensity and was higher with EMS than with VOL, reaching 5.1 (EMS) and 4.7 mmol L^-1 (VOL) at 40 W (P < 0.05). The study demonstrates that electrically induced dynamic exercise is associated with a marked cardiovascular response similar to voluntarily performed exercise and a more pronounced activation of the anaerobic metabolism of the muscle. Furthermore, as the electrically activated muscle group is well defined, the present results confirm that peak muscle blood flow can reach 200–250 mL 100 g^-1 min^-1.