| 1. |
- Ekelund, Ulf, et al.
(author)
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Alpha 2-adrenoceptor activation may trigger the increased production of endothelium-derived nitric oxide in skeletal muscle during acute haemorrhage
- 1998
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In: Acta Physiologica Scandinavica. - 0001-6772. ; 164:3, s. 285-292
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Journal article (peer-reviewed)abstract
- Our previous studies indicated that acute haemorrhage leads to a pronounced increase in the release of endothelium-derived nitric oxide (EDNO) graded in relation to the magnitude of the blood loss. The EDNO-induced vasodilatation, confined selectively to the arterial 'feeder' vessels, attenuates the concomitant reflex adrenergic constriction and thereby prevents deleterious reduction of blood flow. The present study aimed at investigating whether the reflex release of blood-borne catecholamines might trigger this EDNO release via activation of endothelial alpha 2-adrenoceptors. The study was performed on the sympathectomized vascular bed of cat skeletal muscle with a technique permitting quantitative recordings of resistance (tone) in consecutive vascular sections. Selection alpha 2-adrenoceptor blockade with idazoxan applied at steady state vasoconstriction after a 35% blood loss evoked an initial generalized dilator response (attributable to inhibition of post-synaptic smooth muscle alpha 2-adrenoceptors), followed by a constrictor response selectively in the arterial feeder vessels, the latter compatible with the hypothesis of reduced EDNO release by alpha 2-adrenoceptor blockade. More direct evidence for the hypothesis was obtained from studies of the vascular response to EDNO blockade (L-NAME) after haemorrhage in the presence and absence of alpha 2-adrenoceptor blockade. The constrictor response to EDNO blockade, which is a measure of the pre-existing EDNO dilator influence (EDNO production), was significantly smaller (P < 0.01) in the presence than absence of alpha 2-adrenoceptor blockade. The results indicate that blood-borne catecholamines, via activation of endothelial alpha 2-adrenoceptors, trigger the increase in the EDNO release in acute haemorrhage, implying a functionally important negative feedback in the integrated control of vascular tone in bleeding.
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| 2. |
- Ekelund, Ulf
(author)
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Effects of angiotensin-converting enzyme inhibition on arterial, venous and capillary functions in cat skeletal muscle in vivo
- 1996
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In: Acta Physiologica Scandinavica. - 0001-6772. ; 158:1, s. 29-37
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Journal article (peer-reviewed)abstract
- The aim of the present study was to analyse quantitatively, on a cat gastrocnemius muscle preparation in vivo, the effects of local angiotensin-converting enzyme (ACE) inhibition by enalaprilat on total regional vascular resistance (tone) and its distribution to the large-bore arterial resistance vessels (> 25 microns), the small arterioles (< 25 microns) and the veins. Associated effects on capillary pressure and fluid exchange were also studied. Close-arterial infusion of enalaprilat (0.05-0.20 mg kg muscle tissue min-1) elicited a moderate dilator response in all three consecutive sections of the muscle vascular bed, an increase in capillary pressure and transcapillary fluid filtration. This dilation could be abolished by the selective bradykinin B2-receptor antagonist Hoe 140 (2 mg kg-1 min-1, i.a.), indicating that the dilator mechanism of ACE inhibition was an increased local concentration of bradykinin, and hardly at all a decreased concentration of angiotensin (AT) II. The generalized dilator response to ACE inhibition along the vascular bed suggested a relatively uniform distribution of ACE from artery to vein and this was further supported by the finding that a close-arterial infusion of AT I (0.04-0.32 microgram kg-1 min-1), which was vasoactive only after conversion to AT II by local ACE, elicited a generalized constrictor response in all three vascular sections. In contrast, infused AT II (0.01-0.16 microgram kg-1 min-1) constricted almost selectively the large-bore arterial vessels. The specific angiotensin AT1-receptor antagonist losartan (2 mg kg-1 min-1, i.a.) abolished the constrictor response to AT II but did not affect vascular tone under control conditions, indicating that AT II is not involved in the initiation of basal vascular tone in muscle. These results, taken together, indicate that under basal conditions vascular ACE contributes to the local control of vascular tone in skeletal muscle by degrading the endogenous dilator bradykinin, and not by converting AT I into vasoconstrictor AT II.
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| 3. |
- Ekelund, Ulf, et al.
(author)
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Effects of the combined ETA and ETB receptor antagonist PD145065 on arteries, arterioles, and veins in the cat hindlimb
- 1995
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In: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 26:Suppl. 3, s. 211-213
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Journal article (peer-reviewed)abstract
- The aim of this study was to describe in quantitative terms the effects of ETA and ETB receptor blockade on vascular tone (resistance) in large-bore arterial resistance vessels (> 25 microns), small arterioles (< 25 microns), and veins in the cat gastrocnemius muscle in vivo. In the muscle vascular bed, the combined ETA and ETB receptor antagonist PD145065 (1 mg/kg/min, intra-arterially) abolished the biphasic vascular responses (dilatation followed by constriction) to both ET-1 (0.4 microgram/kg/min, intra-arterially) and to the selective ETB receptor agonist IRL1620 (3.2 micrograms/kg/min, intra-arterially). In the cat femoral artery and vein in vitro, PD145065 competitively inhibited the contractile responses to both ET-1 and IRL1620. The contractile response to the latter agonist could be evoked only after long-term incubation of the vessels (37 degrees C for 5 days). These results indicate that PD145065 is a potent antagonist at both ETA and ETB receptors in vivo and in vitro. Therefore, this antagonist may prove useful for elucidating the possible physiologic and/or pathophysiologic roles of the endothelins. For example, it was shown that PD145065 had no effect on vascular tone in the resting state, indicating no role for the endothelins in the regulation of basal vascular tone in cat skeletal muscle.
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| 4. |
- Ekelund, Ulf, et al.
(author)
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Endogenous nitric oxide as a physiological regulator of vascular tone in cat skeletal muscle during haemorrhage
- 1996
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In: Acta Physiologica Scandinavica. - 0001-6772. ; 157:4, s. 471-479
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Journal article (peer-reviewed)abstract
- The problem whether endogenous nitric oxide (NO) may serve as a true physiological regulator of vascular tone in vivo was approached by testing its role during graded acute haemorrhage with the aid of the nitric oxide synthase (NOS) inhibitor L-NAME. The study was performed on the vascular bed of cat skeletal muscle with a technique permitting quantitative recordings of vascular resistance in the whole vascular bed (RT) and in its consecutive sections, the proximal arterial resistance ('feeder') vessels (> 25 microns; Ra,prox), the small arterioles (< 25 microns) and the veins. NO blockade by close-arterial L-NAME infusion in the control situation increased RT from 16.3 to 33.0 PRU (+102%), because of a selective increase in Ra,prox by 16.7 PRU. A 35% blood loss per se raised RT from 13.6 to 21.7 PRU. Superimposed NO blockade in this state caused a much stronger vasoconstriction than in the control situation, increasing RT to 60.9 PRU (+181%) and Ra,prox by 40.5 PRU, which indicated an approximately 2.4-fold increase (P < 0.001) in the NO dilator influence in the Ra,prox section above control. The effect was independent of autonomic nerves. The increased NO dilator influence during haemorrhage most likely was caused by an increased production of endothelium-derived nitric oxide (EDNO), The constrictor response to L-NAME was graded in relation to the blood loss (17.5 vs. 35%). The results indicate that EDNO functions as a physiological regulator of vascular tone in the arterial 'feeder' vessels during haemorrhage, serving to counterbalance to a significant extent the concomitant adrenergic constriction, and thereby preventing critical reduction of blood flow and untoward heterogeneous flow distribution within the tissue.
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| 5. |
- Ekelund, Ulf, et al.
(author)
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In vivo receptor characterization of neuropeptide Y-induced effects in consecutive vascular sections of cat skeletal muscle
- 1997
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In: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 120:3, s. 387-392
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Journal article (peer-reviewed)abstract
- 1. It has been suggested that the vasoconstrictor response to neuropeptide Y (NPY) is located in the microvessels and that it increases with reduced vessel diameter. The aim of the present study was to analyse quantitatively, on the cat gastrocnemius muscle preparation in vivo, the effects of NPY on total regional vascular resistance (RT) and its distribution to large-bore arterial resistance vessels (> 25 microns; Ra,prox), small arterioles (< 25 microns; Ra,micro) and the veins (Rv). Associated effects on capillary pressure (Pc,v) and fluid exchange were also studied. 2. Close-arterially infused NPY (1-32 micrograms kg-1 min-1) caused a dose-dependent, slowly developing vasoconstriction in all three vascular sections, yet with a preferential action in the small arterioles. At 32 micrograms kg-1 min-1, NPY raised RT by 133 +/- 22%, Ra,prox by 94 +/- 15%, Ra,micro by 277 +/- 104% and Rv by 81 +/- 11%. However, the veins (ED50 = 3.9 +/- 1.2 micrograms kg-1 min-1) were more sensitive to NPY than both large-bore arterial vessels (ED50 = 7.7 +/- 1.6) and small arterioles (ED50 = 7.0 +/- 1.4). NPY decreased Pc,v due to an increase in the pre-to post-capillary resistance ratio. 3. Close-arterial infusions of Pro34NPY and peptide YY evoked vasoconstrictor responses which did not differ from the response to NPY. In contrast, the Y2-preferring C-terminal fragments: Ac-[Leu28, Leu31]-NPY (24-36) and NPY(13-36) were without effect in the muscle vascular bed. The selective NPY Y1 receptor antagonist BIBP3226 (100 micrograms kg-1 min-1, i.a.) abolished the vascular response to NPY. 4. The present findings indicate that the vasoconstrictor response to NPY in skeletal muscle is preferentially located in the small arterioles and mediated via the Y1 receptor and, further, that Y2 and Y3 receptors do not play a significant role in the vasoconstrictor response to NPY in cat skeletal muscle. BIBP3226 was found to be an effective NPY antagonist in vivo and to lack agonist activity.
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| 6. |
- Ekelund, Ulf, 1960-, et al.
(author)
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Total daily energy expenditure and patterns of physical activity in adolescents assessed by two different methods
- 1999
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In: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 9:5, s. 257-264
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Journal article (peer-reviewed)abstract
- Minute-by-minute heart rate monitoring and an activity diary were used simultaneously during three days in 30 randomly selected adolescents (16 boys, 14 girls; mean age 15.0+/-1.0). Total daily energy expenditure (TDEE) and its components (energy expenditure during sleep, during rest and in physical activity) and times spent at different intensity levels (sedentary, light, moderate physical activity and vigorous physical activity) were compared. TDEE from heart rate monitoring averaged 10.9+/-2.7 MJ x d(-1) compared to 11.3+/-2.3 MJ x d(-1) from the activity diary (NS). The limits of agreement (mean+/-2 SD) were -3.54 MJ x d(-1) and 2.74 MJ x d(-1). There was no significant difference for any of the TDEE components between the methods (MANOVA). A significant method effect (P<0.001) was observed for time spent in sedentary and light physical activity (MANOVA). No significant difference was observed for time spent in moderate and vigorous physical activity. According to this, heart rate monitoring and activity diary are comparable for group assessment of TDEE and its components, and for estimating time spent in moderate and vigorous physical activity. The activity diary underestimated time spent in moderate and vigorous physical activity for inactive subjects and consequently overestimated highly active subjects.
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| 7. |
- Hickner, R C, et al.
(author)
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Muscle blood flow in cats: comparison of microdialysis ethanol technique with direct measurement
- 1995
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In: Journal of Applied Physiology. - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 79:2, s. 638-647
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Journal article (peer-reviewed)abstract
- A quantitative validation of the microdialysis ethanol technique was performed in cat gastrocnemius muscle. Six to eight microdialysis probes were inserted into the isolated muscle preparation and perfused (0.5-10.0 microliters/min) with Krebs-Henseleit buffer containing between 5 and 1,000 mmol/l ethanol. Skeletal muscle blood flow was held constant in the range of 4-99 ml.100 g-1.min-1 by a servo-controlled roller pump and was determined with the microdialysis ethanol technique as well as by timed collection of venous outflow. The ethanol concentration outflow-to-inflow ratio ([ethanol]collected dialysate/[ethanol]infused perfusion medium) decreased in a nonlinear fashion when microdialysis perfusion flow rates of 0.5 and 1.0 microliter/min were employed. However, a linear decrease was found between 4 and approximately 45 ml.100 g-1.min-1 (r = -0.92 to -0.99). The lower outflow-to-inflow ratio was at 4 ml.100 g-1.min-1 (i.e., due to a low probe perfusion flow rate or a large dialysis membrane), the greater the sensitivity of the method was. It is concluded that this nonradioactive technique provides a simple and valid method for determining nutritive blood flow in skeletal muscle.
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| 8. |
- Jahr, John, et al.
(author)
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In vivo effects of prostacyclin on segmental vascular resistances, on myogenic reactivity, and on capillary fluid exchange in cat skeletal muscle
- 1995
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In: Critical Care Medicine. - 1530-0293. ; 23:3, s. 523-531
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To analyze the local circulatory effects of prostacyclin in skeletal muscle. DESIGN: A prospective experimental study. SETTING: A university laboratory. SUBJECTS: Twelve adult cats. INTERVENTIONS: The study was performed on autoperfused, sympathectomized gastrocnemius muscle. MEASUREMENTS AND MAIN RESULTS: Arterial blood flow, total and segmental vascular resistances (arterial vessels of > 25 microns, arterioles of < 25 microns, and veins), hydrostatic capillary pressure, tissue volume, myogenic reactivity, and the capillary filtration coefficient were followed. The capillary filtration coefficient reflects the functional capillary fluid exchange area. Myogenic reactivity was evaluated as the arteriolar resistance increase after a standardized decrease in extravascular pressure. Arterial infusion of prostacyclin decreased vascular resistance by approximately 50% at the highest dose given (500 ng/kg/min). This effect was more pronounced on the arterial side, especially in arterial vessels of > 25 microns. Hydrostatic capillary pressure increased by 1.9 +/- 0.3 mm Hg, causing fluid filtration. The relative fluid filtration was less than that value shown for some other vasodilator drugs (isoprenaline, calcium-channel blockers, thiopental) in this muscle preparation. Capillary filtration coefficient decreased by 25%. Myogenic reactivity was depressed but to a lesser extent than previously observed for other vasodilator mechanisms (muscle exercise, beta-adrenergic receptor stimulation, thiopental infusion, nifedipine infusion). CONCLUSIONS: Prostacyclin is a vasodilator, both on the arterial and venous side, that restricts the increase in hydrostatic capillary pressure. The decrease in capillary filtration coefficient most likely reflects a decrease in capillary permeability, explaining the smaller relative filtration rate. The relatively well-preserved myogenic reactivity may imply a better preserved microvascular flow distribution and peripheral oxygen uptake.
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| 9. |
- Mellander, Stefan, et al.
(author)
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Cardiovascular regulation by endogenous nitric oxide is essential for survival after acute haemorrhage
- 1997
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In: Acta Physiologica Scandinavica. - 0001-6772. ; 160:1, s. 57-65
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Journal article (peer-reviewed)abstract
- Our previous studies have indicated that endogenous nitric oxide serves as a physiologically important inhibitor of vascular tone during acute haemorrhage. This vasodilator action attenuates the concomitant reflex adrenergic constriction and thereby prevents critical reduction of tissue blood flow. The present study aimed to evaluate the overall importance of this nitric oxide regulation for survival after acute haemorrhage. This was done by comparative observations of survival time and circulatory, metabolic and histopathological changes after an acute standardized lethal blood loss (45%) in cats exposed to nitric oxide synthase (NOS) inhibition and in matched control animals with intact nitric oxide regulation. NOS inhibition was instituted by intravenously administered N omega-nitro-L-arginine methyl ester. The survival time averaged 2 h 49 min in the NOS-blocked animals and 10 h 14 min in the control animals (P < 0.001). NOS inhibition thus reduced the posthaemorrhagic survival time to < 30% of that in the control cats. Haemorrhage in the NOS-blocked animals led to rapidly developing arterial hypotension, increased anaerobic metabolism, metabolic lactacidosis, hyperkalaemia, and morphological tissue damage especially in heart and liver, in spite of maintained arterial normoxia, which signifies tissue hypoxia caused by seriously impaired nutritional blood supply. At the time of death of the NOS-blocked cats, the control animals still exhibited a virtually normal circulatory/metabolic state. A much later, and more slowly developing circulatory/metabolic deterioration was observed in the control animals. These differences between the two groups of animals indicate that nitric oxide release, by its vasodilator action, to a significant extent helps to maintain an adequate nutritional blood supply to the tissues in acute haemorrhage.
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| 10. |
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