The Effects of Cardioselective and Non-Selective β-Adrenoceptor Blockade on the Hypokalaemic and Cardiovascular Responses to Adrenomedullary Hormones in Man

Struthers, Allan D.; Reid, JL; Whitesmith, R.; Rodger, J C

doi:10.1042/cs0650143

Cited by 107 publications

(26 citation statements)

References 18 publications

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“…Epinephrine infusion lengthens QTc interval in normal participants (34), predominantly through a ␤-adrenoceptor-mediated process, whereby the cardiac action potential is prolonged by delayed inactivation of inward calcium currents (35). In this study, we observed a relationship, albeit weak, between the magnitude of the hypoglycemic epinephrine response and the degree of QTc lengthening.…”

Section: Discussionmentioning

confidence: 53%

Influence of Autonomic Neuropathy on QTc Interval Lengthening During Hypoglycemia in Type 1 Diabetes

et al. 2004

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Hypoglycemia produces electrocardiographic QTc lengthening, a predictor of arrhythmia risk and sudden death. This results from both sympatho-adrenal activation and a lowered serum potassium. It has been suggested that cardiac autonomic neuropathy (CAN) might indicate those who are at particular risk. We tested this hypothesis in 28 adults with type 1 diabetes and 8 nondiabetic control subjects. After standard tests of autonomic function and baroreflex sensitivity (BRS) measurement, diabetic participants were divided into three groups: 1) CAN؊ with normal BRS (BRS؉; n ‫؍‬ 10), 2) CAN؊ with impaired BRS (BRS؊; n ‫؍‬ 9), and 3) CAN؉ (n ‫؍‬ 9). QTc was then measured during controlled hypoglycemia (2.5 mmol/l) using a hyperinsulinemic clamp. Mean (؎SE) QTc lengthened from 377 ؎ 9 ms (baseline) to a maximum during hypoglycemia of 439 ؎ 13 ms in BRS؉ subjects and from 378 ؎ 5 to 439 ؎ 10 ms in control subjects. Peak QTc tended to be lower in CAN؉ (baseline, 383 ؎ 6; maximum, 408 ؎ 10) and BRS؊ groups (baseline, 380 ؎ 8; maximum, 421 ؎ 11; F ‫؍‬ 1.7, P ‫؍‬ 0.18). Peak epinephrine concentrations (nmol/l) were 3.1 ؎ 0.8 (BRS؉), 2.6 ؎ 0.5 (BRS؊), 1.4 ؎ 0.3 (CAN؉), and 5.7 ؎ 0.8 (control subjects). These data do not indicate that those with CAN are at particular risk for abnormal cardiac repolarization during hypoglycemia. Indeed, they suggest that such patients may be relatively protected, perhaps as a result of attenuated sympatho-adrenal responses. Diabetes 53: [1535][1536][1537][1538][1539][1540][1541][1542] 2004

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Section: Discussionmentioning

confidence: 53%

Influence of Autonomic Neuropathy on QTc Interval Lengthening During Hypoglycemia in Type 1 Diabetes

et al. 2004

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“…In the skeletal muscle of other animal species such as cats (Minneman et al, 1979), cattle (Ijzerman et al, 1984), guinea pigs (Elfellah & Reid, 1987b) and rabbits ) the ,-adrenoceptors are exclusively of the 02-adrenoceptor subtype. The presence of 32-adrenoceptor binding sites on membranes together with the large pool of potassium which is within skeletal muscle is consistent with the involvement of these receptors in short term regulation of plasma potassium (Lockwood & Lum, 1974;Clausen & Flatman, 1980;Struthers et al, 1983;Brown et al, 1983). The density and affinity of the receptors for ICYP in both rectus abdominis and vastus lateralis muscles were similar, suggesting the former was representative of skeletal muscle in man.…”

Section: Discussionmentioning

confidence: 57%

“…Furthermore 3-adrenoceptors in skeletal muscle have been suggested to maintain physiological concentrations of potassium in plasma especially during exercise and stress and also to mediate the hypokalaemic response to P2-adrenoceptor agonists in animals and man (Lockwood & Lum, 1974;Brown et al, 1983;Struthers et al, 1983;Brown, 1985;Williams etal., 1985;Haalboom et al, 1985;Elfellah & Reid, 1987a). Recent studies have shown that in various animal species the skeletal muscle 3-adrenoceptors are of the 32-subtype (Minneman et al, 1979;Ijzerman et al, 1984;Elfellah & Reid, 1987b).…”

Section: Introductionmentioning

confidence: 99%

Beta‐adrenoceptors and human skeletal muscle characterisation of receptor subtype and effect of age.

Elfellah

Dalling

Kantola

et al. 1989

Brit J Clinical Pharma

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1 Rectus abdominis muscle biopsies were obtained from 28 patients undergoing abdominal surgery. In membranes prepared from these biopsies ,-adrenoceptor binding was examined. The apparent affinity (KD) and the density (Bmax) of the receptors for the radioligand (_)_[1251 cyanopindolol were 28.5 ± 2.7 (pM) and 25.9 ± 2.1 (fmol mg-, protein) (mean ± s.e. mean) respectively. In forceps biopsies from vastus lateralis muscle from four healthy volunteers the values for KD and Bmax were 22.5 ± 4.4 (pM) and 16.4 ± 2.2 (fmol mg-' protein). The binding characteristics for the radioligand were similar in the biopsies from the two muscle sites.2 Inhibition of the radioligand binding by the selective P2-adrenoceptor antagonist ICI 118551 (KI = 117 ± 45 nM) and selective 131-adrenoceptor antagonist metoprolol (K1 = 15229 ± 5046 nM) suggests the dominance of 132-adrenoceptor subtype in human skeletal muscle. 3 There were no significant differences in the skeletal muscle ,-adrenoceptor densities or affinities between the young and older patients.

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“…A lower dose infusion in man produces hypokalaemia with no initial hyperkalaemia (Struthers et al, 1983).…”

Section: Potassiummentioning

confidence: 99%

Effects of selective beta 2‐adrenoceptor blockade on serum potassium and exercise performance in normal men.

Gullestad

Birkeland

Nordby

et al. 1991

Brit J Clinical Pharma

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3 Cumulative work was significantly reduced by ICI-118551 (6.4%, P = 0.04) and by propranolol (12.4%, P < 0.01), whereas the reduction with atenolol (5.6%) did not reach statistical significance. 4 Atenolol and propranolol reduced peak heart rate by 23% and 29%, and peak systolic blood pressure by 9% and 11% respectively during maximal exercise. ICI-118551 caused a non-significant reduction in heart rate during submaximal exercise, with a significant reduction at maximum exercise (6% reduction), whereas systolic blood pressure was not different from placebo. Diastolic blood pressures were similar across all treatment regimens. 5 Similar glucose concentrations were obtained at baseline and at exhaustion during all treatment regimens. Lactate concentrations were comparable for any given exercise intensity irrespective of treatment regimens. Propranolol reduced lactate concentrations from the exercising muscles at maximum exercise in proportion to the reduction of maximal exercise capacity.6 The subjective perception of fatigue was not affected by either 13l-or P2-adrenoceptor blockade.7 In a separate study, the effects of selective P2-adrenoceptor stimulation (terbutaline) in resting men on heart rate, systolic blood pressure, serum potassium and glucose were completely blocked by the doses of ICI-118551 used in the exercise study.8 We conclude that both ,l-and ,32-adrenoceptors are of importance for maximal short term exercise performance in healthy young men. The decisive mechanism for the reduction in exercise performance during ,-adrenoceptor blockade is unclear.The present study suggests that other mechanisms than haemodynamic and metabolic factors are of importance. The lack of effect of selective ,32-adrenoceptor antagonists on serum potassium at rest and during exercise, and the finding that the rate of decline in the potassium concentrations after exhaustion was independent of treatment regimens, suggests that ,3-adrenoceptors are of minor importance for potassium release or reuptake in the exercising muscle.

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The Effects of Cardioselective and Non-Selective β-Adrenoceptor Blockade on the Hypokalaemic and Cardiovascular Responses to Adrenomedullary Hormones in Man

Cited by 107 publications

References 18 publications

Influence of Autonomic Neuropathy on QTc Interval Lengthening During Hypoglycemia in Type 1 Diabetes

Influence of Autonomic Neuropathy on QTc Interval Lengthening During Hypoglycemia in Type 1 Diabetes

Beta‐adrenoceptors and human skeletal muscle characterisation of receptor subtype and effect of age.

Effects of selective beta 2‐adrenoceptor blockade on serum potassium and exercise performance in normal men.

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