Haemodynamic and Metabolic Effects of α-Adrenoceptor Blockade with Phentolamine at Rest and during Forearm Exercise

1983 ◽  
Vol 65 (3) ◽  
pp. 247-253 ◽  
Author(s):  
O. J. Hartling ◽  
J. Trap-Jensen

1. The pre- and post-junctional α-adrenoceptor blocking agent, phentolamine, was given by intravenous infusion to eight healthy volunteers during rest, forearm exercise and post-exercise. 2. Phentolamine produced a sustained increase in heart rate. The diastolic blood pressure decreased slightly whereas systolic and mean blood pressures remained unchanged. Phentolamine caused a marked increase in the forearm blood flow and a decrease in vascular resistance at rest and post-exercise, but did not influence the blood flow or vascular resistance in the exercising forearm. 3. There was a small increase in arterial blood glucose concentration, and a decrease in blood alanine concentration during drug infusion. Blood lactate was not affected by phentolamine. The arterial concentrations of free fatty acids and glycerol increased, and the concentration of triglycerides decreased during phentolamine infusion. 4. Forearm exchange of glucose, lactate, alanine, glycerol, free fatty acids, triglycerides and forearm oxygen consumption were not changed significantly. 5. These findings corroborate the concept that α-adrenoceptor induced vasoconstriction plays a subordinate role in exercising skeletal muscle. All of the metabolic findings might be explained as secondary to an increased noradrenaline release during phentolamine infusion.

1971 ◽  
Vol 125 (2) ◽  
pp. 541-544 ◽  
Author(s):  
R. A. Hawkins ◽  
K. G. M. M. Alberti ◽  
C. R. S. Houghton ◽  
D. H. Williamson ◽  
H. A. Krebs

1. Sodium acetoacetate was infused into the inferior vena cava of fed rats, 48h-starved rats, and fed streptozotocin-diabetic rats treated with insulin. Arterial blood was obtained from a femoral artery catheter. 2. Acetoacetate infusion caused a fall in blood glucose concentration in fed rats from 6.16 to 5.11mm in 1h, whereas no change occurred in starved or fed–diabetic rats. 3. Plasma free fatty acids decreased within 10min, from 0.82 to 0.64mequiv./l in fed rats, 1.16 to 0.79mequiv./l in starved rats and 0.83 to 0.65mequiv./l in fed–diabetic rats. 4. At 10min the plasma concentration rose from 20 to 49.9μunits/ml in fed unanaesthetized rats and from 6.4 to 18.5μunits/ml in starved rats. There was no change in insulin concentration in the diabetic rats. 5. Nembutal-anaesthetized fed rats had a more marked increase in plasma insulin concentration, from 30 to 101μunits/ml within 10min. 6. A fall in blood glucose concentration in fed rats and a decrease in free fatty acids in both fed and starved rats is to be expected as a consequence of the increase in plasma insulin. 7. The fall in the concentration of free fatty acids in diabetic rats may be due to a direct effect of ketone bodies on adipose tissue. A similar effect on free fatty acids could also be operative in normal fed or starved rats.


1981 ◽  
Vol 60 (6) ◽  
pp. 675-679 ◽  
Author(s):  
O. J. Hartling ◽  
T. Lysbo Svendsen ◽  
J. Trap-Jensen

1. The immediate haemodynamic and metabolic effects of intravenous administration of dl-propranolol and d-propranolol were studied in healthy male subjects at rest and during dynamic forearm exercise. The dose of dl-propranolol and of d-propranolol was 0.1 and 1.0 mg/kg body weight respectively. 2. dl-Propranolol reduced heart rate significantly at rest, during forearm exercise and post-exercise, whereas d-propranolol had a lesser effect on heart rate which was significant only at the end of the exercise period. Arterial blood pressure and forearm blood flow were unchanged after either drug. 3. Both drugs reduced the release of lactate from the exercising forearm. Forearm exchange of oxygen, glucose, free fatty acids and triglycerides remained unchanged. 4. The arterial blood glucose concentration increased after d-propranolol, but was unchanged after dl-propranolol. The arterial serum free fatty acid concentration decreased after dl-propranolol, but was not changed after d-propranolol. Arterial concentrations of lactate and triglycerides were not influenced by the drugs. 5. The chronotropic response to β-adrenoceptor blockade appears to be stereoselective, suggesting specific blockade of β-adrenoceptors. Metabolic responses to β-adrenoceptor blockade are difficult to explain in terms of the known adrenoceptor system and may be due to nonspecific actions of β-adrenoceptor antagonists. An exception is inhibition of lipolysis, which is probably mediated via β-adrenoceptors.


1980 ◽  
Vol 58 (4) ◽  
pp. 279-286 ◽  
Author(s):  
O. J. Hartling ◽  
I. Noer ◽  
T. L. Svendsen ◽  
J. P. Clausen ◽  
J. Trap-Jensen

1. The immediate effects of selective (β1) and non-selective (β1+2) β-adrenoreceptor blockade on local blood flow and substrate exchange were studied in young male subjects at rest and during dynamic forearm exercise. After a control period of rest, exercise and recovery, atenolol (β1), propranolol (β1+2) or placebo was infused into the right brachial artery during a second period of rest, exercise and recovery. 2. Neither atenolol nor propranolol influenced forearm blood flow during exercise. Atenolol and propranolol reduced the increase in lactate release from the forearm during exercise by 39 and 34% respectively. Neither agent influenced oxygen and glucose uptake. Propranolol increased forearm uptake of free fatty acids during exercise by 135%. A concomitant fall in forearm respiratory quotient indicated an increased utilization of free fatty acids. Atenolol did not affect free fatty acids uptake or respiratory quotient. 3. Blockade of vascular β2-receptors does not seem to be important for the blood flow regulation during muscular exercise. Both selective and non-selective β-adrenoreceptor blockade reduce the lactate release from exercising skeletal muscle, but appear to have different effects on fat metabolism.


2002 ◽  
Vol 102 (5) ◽  
pp. 495-500 ◽  
Author(s):  
Mark T. KEARNEY ◽  
Philip J. CHOWIENCZYK ◽  
Sally E. BRETT ◽  
Angela SUTCLIFFE ◽  
James M. RITTER ◽  
...  

Circulating free fatty acids (FFA) are elevated in subjects with insulin resistance and Type II diabetes, and increase during myocardial ischaemia, but their haemodynamic effects are incompletely understood. During an investigation of the effects of FFA on endothelial function, we administered lipid emulsion (150mgċmin-1 of soybean oil) with heparin (0.2 unitċkg-1ċmin-1) intravenously to eight healthy men for 2h. This increased circulating FFA to 3.1±0.5mmol/l. Forearm blood flow was measured by venous occlusion plethysmography during brachial artery infusions of saline, acetylcholine and nitroprusside before, and at 1 and 2h. Lipid/heparin infusion had no significant effect on vasodilation to nitroprusside but progressively increased responses to acetylcholine (from 6.3±2.0 during 30μgċmin-1 before-lipid infusion to 7.9±1.3 at 1h and 12.2±1.1mlċmin-1ċ100ml-1 at 2h, P < 0.001). Basal flow increased from 2.7±0.7 to 4.7±0.8mlċmin-1ċ100ml-1 from 0 to 2h. We performed a second study to clarify this effect on basal blood flow. Healthy men (n = 8) received, on separate occasions, 4h intravenous infusions of lipid emulsion with heparin and, as a control, saline with heparin. Lipid with heparin increased mean arterial blood pressure (maximum increment 8.2±2.7mmHg, P < 0.01 compared with saline/heparin control) and forearm blood flow (from 1.7±0.2 to 2.9±0.3mlċmin-1ċ100ml-1, P < 0.01) without a significant effect on heart rate, and reduced calculated forearm vascular resistance (from 49.1±5.4 to 31.3±3.9 arbitrary units, P < 0.01). In conclusion, acute elevation of FFA in healthy men increases arterial blood pressure and reduces vascular resistance. These haemodynamic changes could be clinically relevant.


1997 ◽  
Vol 78 (5) ◽  
pp. 805-813 ◽  
Author(s):  
Kjell Holtenius ◽  
Paul Holtenius

The metabolic effects of a phlorizin-induced drainage of glucose were studied in six lactating ewes with or without peroral alanine drenches in a study of crossover design. Phlorizin gave rise to a small, but significant, elevation of plasma β-hydroxybutyrate. The plasma level of alanine decreased by about 30 % due to the phlorizin injections and alanine was negatively correlated to β-hydroxybutyrate. The plasma level of free fatty acids increased due to phlorizin. Plasma insulin and glucose concentrations were not significantly affected by phlorizin while glucagon level showed a small but significant increase. Peroral alanine drenches to phlorizin-treated ewes gave rise to a transitory elevation of alanine in plasma. The plasma level of free fatty acids was about 40 % lower in phlorizin-treated ewes receiving alanine and β-hydroxybutyrate tended to be lower (P < 0.08). We suggest that β-hydroxybutyrate, apart from its function as an oxidative fuel, might play an important role by limiting glucose oxidation and protein degradation in skeletal muscles during periods of negative energy balance in ruminants. Furthermore, it is suggested that alanine supplementation decreases lipolysis and ketogenesis in lactating ewes.


1997 ◽  
Vol 273 (3) ◽  
pp. R1126-R1131 ◽  
Author(s):  
Y. X. Wang ◽  
J. T. Crofton ◽  
S. L. Bealer ◽  
L. Share

The greater pressor response to vasopressin in male than in nonestrous female rats results from a greater increase in total peripheral resistance in males. The present study was performed to identify the vascular beds that contribute to this difference. Mean arterial blood pressure (MABP) and changes in blood flow in the mesenteric and renal arteries and terminal aorta were measured in conscious male and nonestrous female rats 3 h after surgery. Graded intravenous infusions of vasopressin induced greater increases in MABP and mesenteric vascular resistance and a greater decrease in mesenteric blood flow in males. Vasopressin also increased renal vascular resistance to a greater extent in males. Because renal blood flow remained unchanged, this difference may be due to autoregulation. The vasopressin-induced reduction in blood flow and increased resistance in the hindquarters were moderate and did not differ between sexes. Thus the greater vasoconstrictor response to vasopressin in the mesenteric vascular bed of male than nonestrous females contributed importantly to the sexually dimorphic pressor response to vasopressin in these experiments.


1979 ◽  
Vol 46 (2) ◽  
pp. 288-292 ◽  
Author(s):  
Y. A. Mengesha ◽  
G. H. Bell

Ten to fifteen healthy subjects, ages 18--30 yr, were used to assess the correlation of forearm blood flow with graded passive body tilts and vascular resistance and also to discern the relative effects of body tilts on finger blood flow. In the head-up tilts forearm blood flow and arterial blood pressure fell progressively, whereas forearm vascular resistance and pulse rate increased. In the head-down tilts the forearm blood flow and the arterial blood pressure increased, whereas the forearm vascular resistance and pulse rate decreased. These changes were found to be significantly correlated with the different tilt angles and with one another. In a preliminary study it was found that infrared heating of the carpometacarpal region produced finger vasodilatation similar to the forearm vasodilatation observed by Crockford and Hellon (6). However, unlike forearm blood flow, finger blood flow showed no appreciable response to either the head-up or head-down tilts. This indicates that the sympathetic tone and the volume of blood in the finger are not appreciably altered by this test procedure at least 1 min after the body tilt is assumed.


2002 ◽  
Vol 93 (6) ◽  
pp. 1966-1972 ◽  
Author(s):  
Maria T. E. Hopman ◽  
Jan T. Groothuis ◽  
Marcel Flendrie ◽  
Karin H. L. Gerrits ◽  
Sibrand Houtman

The purpose of the present study was to determine the effect of a spinal cord injury (SCI) on resting vascular resistance in paralyzed legs in humans. To accomplish this goal, we measured blood pressure and resting flow above and below the lesion (by using venous occlusion plethysmography) in 11 patients with SCI and in 10 healthy controls (C). Relative vascular resistance was calculated as mean arterial pressure in millimeters of mercury divided by the arterial blood flow in milliliters per minute per 100 milliliters of tissue. Arterial blood flow in the sympathetically deprived and paralyzed legs of SCI was significantly lower than leg blood flow in C. Because mean arterial pressure showed no differences between both groups, leg vascular resistance in SCI was significantly higher than in C. Within the SCI group, arterial blood flow was significantly higher and vascular resistance significantly lower in the arms than in the legs. To distinguish between the effect of loss of central neural control vs. deconditioning, a group of nine SCI patients was trained for 6 wk and showed a 30% increase in leg blood flow with unchanged blood pressure levels, indicating a marked reduction in vascular resistance. In conclusion, vascular resistance is increased in the paralyzed legs of individuals with SCI and is reversible by training.


1988 ◽  
Vol 66 (1) ◽  
pp. 101-105 ◽  
Author(s):  
P. Kubes ◽  
C. K. Chapler ◽  
S. M. Cain

Redistribution of blood flow away from resting skeletal muscle does not occur during anemic hypoxia even when whole body oxygen uptake is not maintained. In the present study, the effects of sympathetic nerve stimulation on both skeletal muscle and hindlimb blood flow were studied prior to and during anemia in anesthetized, paralyzed, and ventilated dogs. In one series (skeletal muscle group, n = 8) paw blood flow was excluded by placing a tourniquet around the ankle; in a second series (hindlimb group, n = 8) no tourniquet was placed at the ankle. The distal end of the transected left sciatic nerve was stimulated to produce a maximal vasoconstrictor response for 4-min intervals at normal hematocrit (Hct.) and at 30 min of anemia (Hct. = 14%). Arterial blood pressure and hindlimb or muscle blood flow were measured; resistance and vascular hindrance were calculated. Nerve stimulation decreased blood flow (p < 0.05) in the hindlimb and muscle groups at normal Hct. Blood flow rose (p < 0.05) during anemia and was decreased (p < 0.05) in both groups during nerve stimulation. However, the blood flow values in both groups during nerve stimulation in anemic animals were greater (p < 0.05) than those at normal Hct. Hindlimb and muscle vascular resistance fell significantly during anemia and nerve stimulation produced a greater increase in vascular resistance at normal Hct. Vascular hindrance in muscle, but not hindlimb, was less during nerve stimulation in anemia than at normal Hct. The data indicate that (i) maximal sympathetic stimulation produced a significant decrease in both skeletal muscle and hindlimb blood flow during anemia, (ii) the reduction in blood flow in these areas was less with sympathetic stimulation during anemia than at normal Hct., and (iii) the anemic stimulus (Hct. = 14%) does not activate maximal sympathetic vasoconstrictor tone in the skeletal muscle.


2002 ◽  
Vol 282 (2) ◽  
pp. E402-E411 ◽  
Author(s):  
Chang An Chu ◽  
Stephanie M. Sherck ◽  
Kayano Igawa ◽  
Dana K. Sindelar ◽  
Doss W. Neal ◽  
...  

The aim of this study was to determine the effect of high levels of free fatty acids (FFA) and/or hyperglycemia on hepatic glycogenolysis and gluconeogenesis. Intralipid was infused peripherally in 18-h-fasted conscious dogs maintained on a pancreatic clamp in the presence (FFA + HG) or absence (FFA + EuG) of hyperglycemia. In the control studies, Intralipid was not infused, and euglycemia (EuG) or hyperglycemia (HG) was maintained. Insulin and glucagon were clamped at basal levels in all four groups. The arterial blood glucose level increased by 50% in the HG and FFA + HG groups. It did not change in the EuG and FFA + EuG groups. Arterial plasma FFA increased by ∼140% in the FFA + EuG and FFA + HG groups but did not change significantly either in the EuG or HG groups. Arterial glycerol levels increased by ∼150% in both groups. Overall (3-h) net hepatic glycogenolysis was 196 ± 26 mg/kg in the EuG group. It decreased by 96 ± 20, 82 ± 16, and 177 ± 22 mg/kg in the HG, FFA + EuG, and FFA + HG groups, respectively. Overall (3-h) hepatic gluconeogenic flux was 128 ± 22 mg/kg in the EuG group, but it was suppressed by 30 ± 9 mg/kg in response to hyperglycemia. It was increased by 59 ± 12 and 56 ± 10 mg/kg in the FFA + EuG and FFA + HG groups, respectively. In conclusion, an increase in plasma FFA and glycerol significantly inhibited hepatic glycogenolysis and markedly stimulated hepatic gluconeogenesis.


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