The role of α-adrenergic receptors in carbon monoxide hypoxia

The importance of α-adrenergic receptors in the cardiac output and peripheral circulatory responses to carbon monoxide (CO) hypoxia was studied in anesthetized dogs. Phenoxybenzamine (3 mg/kg i.v.) was injected to block α-receptor activity and the data obtained were then compared with those from a previous study of CO hypoxia in unblocked animals. Values for cardiac output, hindlimb blood flow, vascular resistance, and oxygen uptake were obtained prior to and at 30 and 60 min of CO hypoxia which reduced arterial oxygen content by approximately 50%. α-Adrenergic blockade resulted in a lower (p < 0.05) control value for cardiac output than observed in unblocked animals, but no differences were present between the two groups at 30 or 60 min of CO hypoxia. Similarly, limb blood flow was lower (p < 0.05) during the control period in the α-blocked group but rose to the same level as that in the unblocked animals at 60 min of COH. No change in limb blood flow occurred during CO hypoxia in the unblocked group. These findings demonstrated that during CO hypoxia (i) α-receptor mediated venoconstriction does not contribute to the cardiac output response and (ii) α-receptor mediated vasoconstriction probably does prevent a rise in hindlimb skeletal muscle blood flow.

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Effects of khellin on coronary blood flow and related metabolic functions

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1959.196.2.391 ◽

1959 ◽

Vol 196 (2) ◽

pp. 391-393 ◽

Cited By ~ 6

Author(s):

Richard L. Farrand ◽

Steven M. Horvath

Keyword(s):

Blood Flow ◽

Cardiac Output ◽

Coronary Blood Flow ◽

Control Period ◽

Systemic Arterial Pressure ◽

Arterial Oxygen ◽

Arterial Oxygen Content ◽

Fick Principle ◽

Metabolic Functions ◽

Pulmonary Arterial

Khellin, a drug employed as a coronary dilator, was tested to determine its effects on the cardiovascular system of the dog. Ten mongrel dogs were anesthetized with Nembutal and, after control observations were made, given an intravenous administration of 1 mg/kg body weight of khellin. Coronary blood flow and cardiac output samples were drawn during the control period and at 10, 40 and 80 minutes after administration of the drug Cardiac output was calculated by the direct Fick principle and coronary blood flow by the nitrous oxide method. There was a significant (5%) increase in the arterial oxygen content during the 10- and 40-minute intervals, but no change was observed at 80 minutes. An increase in arterial-mixed venous oxygen difference occurred at 40 and 80 minutes. No change in systemic arterial pressure or cardiac output was noted at any time. Coronary blood flow had decreased slightly at 80 minutes. A significant decrease in carbon dioxide content of the arterial, pulmonary arterial and coronary sinus blood was observed, possibly as a consequence of hyperventilation. Khellin appeared to alter the metabolism of the myocardial and splanchnic tissues.

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Adrenoceptor regulation of canine skeletal muscle blood flow during carbon monoxide hypoxia

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y91-209 ◽

1991 ◽

Vol 69 (10) ◽

pp. 1399-1404 ◽

Cited By ~ 1

Author(s):

P. Kubes ◽

K. A. Nesbitt ◽

S. M. Cain ◽

C. K. Chapler

Keyword(s):

Skeletal Muscle ◽

Carbon Monoxide ◽

Blood Flow ◽

Muscle Blood Flow ◽

Peripheral Blood Flow ◽

Neural Activation ◽

Adrenergic Blockade ◽

Skeletal Muscle Blood Flow ◽

Anesthetized Dogs ◽

Adrenoceptor Regulation

We questioned whether carbon monoxide hypoxia (COH) would affect peripheral blood flow by neural activation of adrenoceptors to the extent we had found in other forms of hypoxia. We studied this problem in hindlimb muscles of four groups of anesthetized dogs (untreated, α1-blocked, α1 + α2-blocked, and β2-blocked). Cardiac output increased, but hindlimb blood flow [Formula: see text] and resistance (RL) remained at prehypoxic levels during COH (O2 content reduced 50%) in untreated animals. When activity in the sciatic nerve was reversibly cold blocked, [Formula: see text] doubled and RL decreased 50%. These changes with nerve block were the same during COH, suggesting that neural activity to hindlimb vasculature was not increased by COH. In animals treated with phenoxybenzamine (primarily α1-blocked), RL dropped (~50%) during COH, an indication that catecholamines played a significant role in maintaining tone to skeletal muscle. Animals with both α1 + α2-adrenergic blockade (phenoxybenzamine and yohimbine added) did not survive COH. RL was higher in β2-block than in the untreated group during COH, but nerve cooling indicated that β2-adrenoceptor vasodilation was accomplished primarily by humoral means. The above findings demonstrated that adrenergic receptors were important in the regulation of [Formula: see text] and RL during COH, but they were not activated by sympathetic nerve stimulation to the limb muscles.Key words: α1-adrenoreceptor blockade, α2-adrenoreceptor blockade, peripheral vascular resistance, skeletal muscle, blood flow.

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Cardiovascular responses to dynamic exercise with acute anemia in humans

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.273.4.h1787 ◽

1997 ◽

Vol 273 (4) ◽

pp. H1787-H1793 ◽

Cited By ~ 29

Author(s):

Maria D. Koskolou ◽

Robert C. Roach ◽

José A. L. Calbet ◽

Göran Rådegran ◽

Bengt Saltin

Keyword(s):

Blood Flow ◽

Cardiac Output ◽

Muscle Blood Flow ◽

Knee Extensor ◽

Hemoglobin Concentration ◽

Cardiovascular Responses ◽

Submaximal Exercise ◽

Peak Exercise ◽

Limb Blood Flow ◽

Maximal Cardiac Output

We hypothesized that reducing arterial O2 content ([Formula: see text]) by lowering the hemoglobin concentration ([Hb]) would result in a higher blood flow, as observed with a low [Formula: see text], and maintenance of O2 delivery. Seven young healthy men were studied twice, at rest and during two-legged submaximal and peak dynamic knee extensor exercise in a control condition (mean control [Hb] 144 g/l) and after 1–1.5 liters of whole blood had been withdrawn and replaced with albumin {mean drop in [Hb] 29 g/l (range 19–38 g/l); low [Hb]}. Limb blood flow (LBF) was higher ( P < 0.01) with low [Hb] during submaximal exercise (i.e., at 30 W, LBF was 2.5 ± 0.1 and 3.0 ± 0.1 l/min for control [Hb] and low [Hb], respectively; P < 0.01), resulting in a maintained O2 delivery and O2 uptake for a given workload. However, at peak exercise, LBF was unaltered (6.5 ± 0.4 and 6.6 ± 0.6 l/min for control [Hb] and low [Hb], respectively), which resulted in an 18% reduction in O2 delivery ( P < 0.01). This occurred despite peak cardiac output in neither condition reaching >75% of maximal cardiac output (∼26 l/min). It is concluded that a low CaO2 induces an elevation in submaximal muscle blood flow and that O2 delivery to contracting muscles is tightly regulated.

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Hindlimb vascular responses to sympathetic augmentation during acute anemia

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y85-130 ◽

1985 ◽

Vol 63 (7) ◽

pp. 782-786 ◽

Cited By ~ 1

Author(s):

Stephen M. Cain ◽

C. K. Chapler

Keyword(s):

Skeletal Muscle ◽

Blood Flow ◽

Sympathetic Activity ◽

Carotid Arteries ◽

Muscle Blood Flow ◽

Recovery Period ◽

Control Period ◽

Whole Body ◽

Block Group ◽

Limb Blood Flow

The effect of increased sympathetic activity on skeletal muscle blood flow during acute anemic hypoxia was studied in 16 anesthetized dogs. Sympathetic activity was altered by clamping the carotid arteries bilaterally below the carotid sinus. One group (n = 8) was beta blocked by administration of propranolol (1 mg/kg); a second group (n = 8) was untreated. Venous outflow from the left hindlimb was isolated for measurement of blood flow and O2 uptake [Formula: see text]. After a 20-min control period, both carotid arteries were clamped (CC) for 20 min followed by a 20-min recovery period. The sequence was repeated after hematocrit was lowered to about 15% by dextran exchange for blood. Prior to anemia, CC did not alter cardiac output or limb blood flow in either group. After induction of anemia, hindlimb resistance was higher with CC in the beta block than in the no block group. Both limb blood flow and [Formula: see text] fell in the β-block group with CC during anemia. Beta block also prevented the additive increases in whole body [Formula: see text] seen with CC and induction of anemia. The data showed that the increased vasoconstrictor tone that was obtained with beta block during anemia was successful in redistributing the lower viscosity blood away from resting skeletal muscle, even to the point that muscle [Formula: see text] was decreased.

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Effect of mild carboxy-hemoglobin on exercising skeletal muscle: intravascular and intracellular evidence

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00226.2002 ◽

2002 ◽

Vol 283 (5) ◽

pp. R1131-R1139 ◽

Cited By ~ 24

Author(s):

R. S. Richardson ◽

E. A. Noyszewski ◽

B. Saltin ◽

J. González-Alonso

Keyword(s):

Blood Flow ◽

Oxygen Uptake ◽

Muscle Blood Flow ◽

Knee Extensor ◽

Arterial Oxygen ◽

Arterial Oxygen Content ◽

Muscle Oxygen ◽

Progressive Exercise ◽

Maximum Work ◽

Young Subjects

We studied muscle blood flow, muscle oxygen uptake (V˙o 2), net muscle CO uptake, Mb saturation, and intracellular bioenergetics during incremental single leg knee-extensor exercise in five healthy young subjects in conditions of normoxia, hypoxia (H; 11% O2), normoxia + CO (COnorm), and 100% O2+ CO (COhyper). Maximum work rates and maximal oxygen uptake (V˙o 2 max) were equally reduced by ≈14% in H, COnorm, and COhyper. The reduction in arterial oxygen content (CaO2 ) (≈20%) resulted in an elevated blood flow (Q) in the CO and H trials. Net muscle CO uptake was attenuated in the CO trials. Suprasystolic cuff measurements of the deoxy-Mb signal were not different in terms of the rate of signal rise or maximum signal attained with and without CO. At maximal exercise, calculated mean capillary Po 2 was most reduced in H and resulted in the lowest Mb-associated Po 2. Reductions in ATP, PCr, and pH during H, COnorm, and COhyper occurred earlier during progressive exercise than in normoxia. Thus the effects of reduced CaO2 due to mild CO poisoning are similar to H.

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Muscle blood flow, hypoxia, and hypoperfusion

Journal of Applied Physiology ◽

10.1152/japplphysiol.00620.2013 ◽

2014 ◽

Vol 116 (7) ◽

pp. 852-857 ◽

Cited By ~ 44

Author(s):

Michael J. Joyner ◽

Darren P. Casey

Keyword(s):

Blood Flow ◽

Oxygen Delivery ◽

Muscle Blood Flow ◽

Oxygen Demand ◽

Arterial Oxygen ◽

Arterial Oxygen Content ◽

Sympathetic Vasoconstriction ◽

Response To Exercise ◽

Metabolic Vasodilation ◽

Hypoxic Exercise

Blood flow increases to exercising skeletal muscle, and this increase is driven primarily by vasodilation in the contracting muscles. When oxygen delivery to the contracting muscles is altered by changes in arterial oxygen content, the magnitude of the vasodilator response to exercise changes. It is augmented during hypoxia and blunted during hyperoxia. Because the magnitude of the increased vasodilation during hypoxic exercise tends to keep oxygen delivery to the contracting muscles constant, we have termed this phenomenon “compensatory vasodilation.” In a series of studies, we have explored metabolic, endothelial, and neural mechanisms that might contribute to compensatory vasodilation. These include the contribution of vasodilating substances like nitric oxide (NO) and adenosine, along with altered interactions between sympathetic vasoconstriction and metabolic vasodilation. We have also compared the compensatory vasodilator responses to hypoxic exercise with those seen when oxygen delivery to contracting muscles is altered by acute reductions in perfusion pressure. A synthesis of our findings indicate that NO contributes to the compensatory dilator responses during both hypoxia and hypoperfusion, while adenosine appears to contribute only during hypoperfusion. During hypoxia, the NO-mediated component is linked to a β-adrenergic receptor mechanism during lower intensity exercise, while another source of NO is engaged at higher exercise intensities. There are also subtle interactions between α-adrenergic vasoconstriction and metabolic vasodilation that influence the responses to hypoxia, hyperoxia, and hypoperfusion. Together our findings emphasize both the tight linkage of oxygen demand and supply during exercise and the redundant nature of the vasomotor responses to contraction.

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The role of aortic chemoreceptors during severe CO hypoxia

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y85-087 ◽

1985 ◽

Vol 63 (5) ◽

pp. 509-514 ◽

Cited By ~ 2

Author(s):

C. E. King ◽

S. M. Cain ◽

C. K. Chapler

Keyword(s):

Carbon Monoxide ◽

Blood Flow ◽

Cardiac Output ◽

Whole Body ◽

Limb Blood Flow ◽

Intact Group ◽

Anesthetized Dogs ◽

Dialysis Method

The importance of aortic chemoreceptors in the circulatory responses to severe carbon monoxide (CO) hypoxia was studied in anesthetized dogs. The aortic chemoreceptors were surgically denervated in eight dogs prior to the induction of CO hypoxia, with nine other dogs serving as intact controls. Values for both whole body and hindlimb blood flow, vascular resistance, and O2 uptake were determined prior to and at 30 min of CO hypoxia in the two groups. Arterial O2 content was reduced 65% using an in situ dialysis method to produce CO hypoxia. At 30 min of hypoxia, cardiac output increased but limb blood flow remained at prehypoxic levels in both groups. This indicated that aortic chemoreceptor input was not necessary for the increase in cardiac output during severe CO hypoxia, nor for the diversion of this increased flow to nonmuscle tissues. Limb O2 uptake decreased during CO hypoxia in the aortic-denervated group but remained at prehypoxic levels in the intact group. The lower resting values for limb blood flow in the aortic-denervated animals required a greater level of O2 extraction to maintain resting O2 uptake. When CO hypoxia was superimposed upon this compensation, an O2 supply limitation occurred because the limb failed to vasodilate even as maximal levels for O2 extraction were approached.

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Regional Blood Flow in Borderline and Sustained Essential Hypertension

Clinical Science ◽

10.1042/cs0600653 ◽

1981 ◽

Vol 60 (6) ◽

pp. 653-658 ◽

Cited By ~ 22

Author(s):

M. M. Temmar ◽

M. E. Safar ◽

J. A. Levenson ◽

J. M. Totomoukouo ◽

A. Ch. Simon

Keyword(s):

Blood Flow ◽

Cardiac Output ◽

Essential Hypertension ◽

Lower Limb ◽

Regional Blood Flow ◽

Muscle Blood Flow ◽

Limb Blood Flow ◽

Normal Range ◽

Borderline Hypertension ◽

Blood Flows

1. Cardiac output, lower-limb blood flow, hepatic and renal blood flows were studied in 16 patients with borderline and 16 patients with sustained essential hypertension and compared with 16 age-matched control subjects. 2. In borderline hypertension cardiac output and lower-limb blood flow were significantly elevated, while hepatic and renal blood flows were within the normal range. Cardiac output and lower-limb blood flow were positively correlated. 3. In sustained hypertension cardiac output, lower-limb blood flow and hepatic blood flow were within the normal range. Renal blood flow was significantly reduced. Lower-limb blood flow was negatively correlated with mean arterial pressure. 4. If borderline hypertension is an early stage of fixed hypertension, the present study suggests that the changes in cardiac output observed in hypertension are mainly related to lower-limb (and muscle) blood flow.

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Human muscle length-dependent changes in blood flow

Journal of Applied Physiology ◽

10.1152/japplphysiol.01223.2011 ◽

2012 ◽

Vol 112 (4) ◽

pp. 560-565 ◽

Cited By ~ 17

Author(s):

John McDaniel ◽

Stephen J. Ives ◽

Russell S. Richardson

Keyword(s):

Blood Flow ◽

Knee Joint ◽

Joint Angle ◽

Muscle Blood Flow ◽

Muscle Length ◽

Limb Blood Flow ◽

Knee Joint Angle ◽

Femoral Blood Flow ◽

Femoral Blood ◽

Cyclic Changes

Although a multitude of factors that influence skeletal muscle blood flow have been extensively investigated, the influence of muscle length on limb blood flow has received little attention. Thus the purpose of this investigation was to determine if cyclic changes in muscle length influence resting blood flow. Nine healthy men (28 ± 4 yr of age) underwent a passive knee extension protocol during which the subjects' knee joint was passively extended and flexed through 100–180° knee joint angle at a rate of 1 cycle per 30 s. Femoral blood flow, cardiac output (CO), heart rate (HR), stroke volume (SV), and mean arterial pressure (MAP) were continuously recorded during the entire protocol. These measurements revealed that slow passive changes in knee joint angle did not have a significant influence on HR, SV, MAP, or CO; however, net femoral blood flow demonstrated a curvilinear increase with knee joint angle ( r2 = 0.98) such that blood flow increased by ∼90% (125 ml/min) across the 80° range of motion. This net change in blood flow was due to a constant antegrade blood flow across knee joint angle and negative relationship between retrograde blood flow and knee joint angle ( r2 = 0.98). Thus, despite the absence of central hemodynamic changes and local metabolic factors, blood flow to the leg was altered by changes in muscle length. Therefore, when designing research protocols, researchers need to be cognizant of the fact that joint angle, and ultimately muscle length, influence limb blood flow.

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