Beta 2-adrenergic Mechanism Research Articles

Cerebral non‐oxidative carbohydrate consumption in humans driven by adrenaline

During brain activation, the decrease in the ratio between cerebral oxygen and carbohydrate uptake [6 O2/(glucose + 1/2lactate); OCI] is attenuated by the non‐selective beta‐adrenergic receptor antagonist propranolol, whereas OCI remains unaffected by the beta1‐adrenergic receptor antagonist metroprolol. These observations suggest involvement of a beta2‐adrenergic mechanism in non‐oxidative metabolism for the brain. Therefore, we evaluated the effect of adrenaline (0.08 micrograms kg‐1 min‐1 iv. for 15 min) and noradrenaline (0.5, 0.1 and 0.15 micrograms kg‐1 min‐1 iv. for 20 min) on the arterial to internal jugular venous concentration differences (a‐v diff) of O2, glucose, and lactate in healthy humans. Adrenaline (n=10) increased the arterial concentrations of O2, glucose and lactate (P < 0.05) and also increased the a‐v diff for glucose from 0.6 ± 0.1 to 0.8 ± 0.2 mM (mean ± SD; P < 0.05). The a‐v diff for lactate shifted from a net cerebral release to an uptake and OCI was lowered from 5.1 ± 1.5 to 3.6 ± 0.4 (P < 0.05) indicating a 8‐fold increase in the rate of non‐oxidative carbohydrate uptake during adrenaline infusion (P < 0.01). Conversely, noradrenaline (n=8) did not affect the OCI despite an increase in the a‐v diff for glucose (P < 0.05). These results support that non‐oxidative carbohydrate consumption for the brain is driven by a beta2‐adrenergic mechanism, making neurons abundantly provided with energy when plasma adrenaline increases.

Role of Presynaptic β2-Adrenergic Facilitation in the Development and Maintenance of DOCA-Salt Hypertension

The present study evaluated the contribution of the presynaptic beta 2-adrenergic facilitation in the increase of plasma norepinephrine levels observed in deoxycorticosterone acetate (DOCA)-salt hypertension. Epinephrine is thought to be the major endogenous activator of this presynaptic mechanism and although basal epinephrine levels were similar in normotensive and DOCA-salt hypertensive rats, the sensitivity of the presynaptic beta 2-adrenergic facilitatory mechanism was found to be increased in hypertensive animals. This was shown in vivo by the enhanced plasma norepinephrine increases induced by a direct presynaptic stimulation with a selective beta 2-adrenergic receptor agonist. Furthermore, the adrenal medulla was hyperreactive in response to a hemorrhagic hypotension of 50 mm Hg, as shown by a greater plasma epinephrine increase in DOCA-salt-treated rats, and tissue concentrations of epinephrine were found to be greatly increased in the aorta of hypertensive animals. The possible contribution of epinephrine activation of the presynaptic beta 2-adrenergic mechanism on the development and maintenance of DOCA-salt hypertension was assessed by evaluating the effects of chronic or acute adrenalectomy, respectively. Acute adrenalectomy decreased significantly the blood pressure only in hypertensive animals, whereas chronic adrenalectomy abolished the plasma norepinephrine and blood pressure differences between normotensive and DOCA-salt-treated rats. The present results therefore suggest that the presynaptic beta 2-adrenergic facilitation is exaggerated in DOCA-salt hypertension, mainly due to an increased sensitivity of this mechanism and to a hyperreactivity of the adrenal medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

Beta-adrenergic blockade attenuates insulin resistance induced by tumor necrosis factor

The macrophage secretory product tumor necrosis factor (TNF) impairs insulin action on peripheral glucose uptake and hepatic glucose output. Because circulating catecholamines are also elevated by TNF, the present study was performed to determine the role of the adrenergic system in eliciting the insulin resistance. Human recombinant TNF (1 microgram.h-1.kg-1) was infused intravenously into chronically catheterized fasted rats for approximately 18 h. Before TNF, an infusion of either saline, propranolol (nonselective beta-antagonist), atenolol (selective beta 1-antagonist), or phentolamine (alpha-antagonist) was started and continued throughout the experimental protocol. Infusion of either the alpha- or beta-receptor antagonist failed to prevent the TNF-induced increase in basal glucose uptake or hepatic glucose output. Under euglycemic hyperinsulinemic conditions, whole body glucose disposal was lower in TNF-infused rats than in control animals. This resulted from a decreased rate of insulin-stimulated glucose uptake by skeletal muscle, skin, and intestine. In propranolol-infused rats, but not in those receiving atenolol or phentolamine, the TNF-induced decrease in whole body glucose uptake was partially prevented. Propranolol attenuated the development of peripheral insulin resistance by selectively preventing the decrease in glucose uptake by skeletal muscle but not by skin and ileum. Propranolol was also able to ameliorate the hepatic insulin resistance produced by TNF. These results suggest that beta-adrenergic stimulation, probably mediated by a beta 2-adrenergic mechanism, is partially responsible for the development of both peripheral and hepatic insulin resistance in animals infused with TNF.

Sepsis-induced insulin resistance in rats is mediated by a beta-adrenergic mechanism.

Bacterial infection decreases insulin-mediated glucose uptake (IMGU) by skeletal muscle and produces whole body insulin resistance. Because circulating catecholamines are elevated by the septic insult, the present study was performed to determine the potential role of the beta-adrenergic system in eliciting these changes. Before induction of sepsis, an infusion containing saline, propranolol, or atenolol was started and continued throughout the experimental protocol. Sepsis increased the basal rate of glucose production and utilization and impaired IMGU by peripheral tissues. The peripheral insulin resistance in septic rats was manifested by an increase in the dose producing 50% of maximal response and a decrease in the maximal responsiveness. Infusion of propranolol, a nonselective beta-adrenergic antagonist, attenuated the sepsis-induced increase in basal glucose turnover by 70% and completely prevented the decrease in IMGU by the whole body. In contrast, atenolol, a selective beta 1-antagonist, did not alter the glucose metabolic response to infection. Under basal conditions, propranolol prevented or attenuated the increase in glucose uptake by the gastrocnemius, diaphragm, skin, liver, lung, spleen, and ileum normally observed in septic rats. In addition, propranolol prevented the decrease in IMGU by various muscles and skin in septic animals. These results suggest that adrenergic stimulation, probably mediated by a beta 2-adrenergic mechanism, is partially responsible for the sepsis-induced increases in basal whole body glucose turnover and plays a prominent role in the development of peripheral insulin resistance in this condition.

Enzymatic adaptation to physical training under beta-blockade in the rat. Evidence of a beta 2-adrenergic mechanism in skeletal muscle.

Nonselective and beta 1-selective adrenergic antagonists were tested for their effects on enzymatic adaptation to exercise training in rats as follows: trained + placebo (TC); trained + propranolol (TP); trained + atenolol (TA); and corresponding sedentary groups, SC and SP. Trained rats ran 1 h/d at 26.8 m/min, 15% grade, 5 d/wk, 10 wk. Both beta-antagonists were given at doses that decreased exercise heart rates by 25%. Training increased skeletal muscle citrate synthase, cytochrome c oxidase (Cyt-Ox), carnitine palmitoyltransferase (CPT), beta-hydroxyacyl coenzyme A dehydrogenase, mitochondrial malate dehydrogenase (MDH), and alanine aminotransferase (ALT) activities significantly in the TC group, but not in TP. These enzyme activities, except Cyt-Ox and CPT, were also significantly increased in TA. Hepatic phosphoenolpyruvate carboxykinase activity did not alter with training or beta-blockade. Fructose 1,6-bisphosphatase activity was lower in TC than in SC, but unchanged in TP or TA. Hepatic mitochondrial MDH and ALT activities increased with training only in TC. It is concluded that beta 2-adrenergic mechanisms play an essential role in the training-induced enzymatic adaptation in skeletal muscle.

Elevation of brachial arterial blood velocity and volumic flow mediated by peripheral beta-adrenoreceptors in patients with borderline hypertension.

Simultaneous determinations of cardiac output and brachial arterial blood flow were performed in patients with hypertension and high cardiac output in comparison with normal subjects of the same age. Brachial arterial blood flow was measured with a previously described pulsed Doppler apparatus that permitted the noninvasive determination of arterial diameter and blood flow velocity. In patients with borderline hypertension, brachial blood flow was significantly increased (136 +/- 11 vs 72 +/- 8 ml/min; p less than .001). After short-term administration of indomethacin, cardiac output decreased while brachial blood flow remained constant. After short-term administration of a selective beta 1-receptor antagonist (primidolol) and nonselective blocker (propranolol), cardiac output decreased significantly in both cases but the decrease in brachial blood flow was significant only after the administration of the nonselective beta-blocking agent. The study strongly suggested that in patients with borderline hypertension, the increased cardiac output is related to a prostaglandin and beta 1-adrenergic mechanisms whereas the increased brachial blood flow depends mainly on beta 2-adrenergic mechanisms.

The Effect of Alpha- and Beta-Adrenergic Agonists and Blockers on Postprandial Pancreatic Polypeptide Release in Dogs

The influence of adrenergic agonists--phenylephrine (alpha), isoproterenol (beta), and salbutamol (beta 2)--and of adrenergic blockers--phentolamine (alpha), pranolol (beta), and practolol (beta 1)--on the postprandial pancreatic polypeptide (PP) release has been assessed in five Labrador retrievers. Infusions of phenylephrine, 0.12 mg kg-1h-1; isoproterenol, 3 micrograms kg-1h-1; salbutamol, 12 micrograms kg-1h-1, did not significantly affect PP release. Propranolol, 0.5 mg kg-1, and propranolol, 0.5 mg kg-1, + phentolamine, 1 mg kg-1, combined, given as intravenous boluses before the meal significantly reduce PP release (44% and 58% of controls, p less than 0.05), whereas phentolamine, 1 mg kg-1, and practolol, 1 mg kg-1, had no effect. Phenylephrine combined with phentolamine and isoproterenol combined with propranolol and practolol did not influence PP secretion. It is concluded that the postprandial PP release is stimulated by beta 2-adrenergic mechanisms.