Metabolic Effects of Atenolol and Doxazosin in Healthy Volunteers During Prolonged Physical Exercise

Cosenzi, Alessandro; Sacerdote, A; Bocin, Elena; Molino, Rossella; Mangiarotti, M; Bellini, Giuseppe

doi:10.1097/00005344-199501000-00022

Cited by 4 publications

(2 citation statements)

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“…This double contribution was suspected since, when using the in situ microdialysis method, part of the exercise-induced lipid mobilization was found to be resistant to the ␤-AR antagonist propranolol (Hellstrom et al, 1996). In addition, a number of studies have demonstrated that oral treatment with ␤-AR antagonists only partially suppressed the exercise-induced lipid mobilization (Bulow, 1981;Cosenzi et al, 1995). Finally, under efficient oral ␤-AR blockade, which initiates a strong ANP release during exercise (Berlin et al, 1993a,b), a recent study in our laboratory has shown that the lipid mobilization promoted by exercise in subcutaneous adipose tissue was related to the action of ANP (Moro et al, 2003).…”

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confidence: 99%

Functional and Pharmacological Characterization of the Natriuretic Peptide-Dependent Lipolytic Pathway in Human Fat Cells

Moro

Galitzky²,

Sengenès³

et al. 2003

J Pharmacol Exp Ther

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A lipolytic pathway involving natriuretic peptides has recently been discovered in human fat cells. Its functional characteristics and the interactions of the atrial natriuretic peptide (ANP)-induced effects with adrenergic and insulin pathways were studied. Characterization of the action of ANP antagonists, i.e., A71915, anantin, S-28-Y (Ser-28-Tyr, a synthesized peptide), and HS-142-1 (a microbial polysaccharide), was performed. Lipolytic assays and intracellular cGMP and cAMP determinations were performed on isolated fat cells. Cell membranes were used for binding studies. At low concentrations ANP and isoproterenol [␤-adrenergic receptor (␤-AR) agonist] exerted additive lipolytic effects. The ␣ 2 -AR pathway did not interfere with that of ANP. Lipolytic effects of ANP were unaltered by a 2-h pretreatment of fat cells with insulin, whereas ␤-AR-induced lipolysis was reduced. Homologous desensitization occurred for ANP-dependent lipolytic pathways. Dendroapsis natriuretic peptide exhibited a similar maximal effect but a 10-fold higher lipolytic potency than ANP and mini-ANP (the shortest form of ANP). The antagonist A71915 exhibited competitive antagonistic properties with a pA 2 value of 7.51. Anantin displayed noncompetitive antagonism and exerted an inhibitory action on basal and ␤-adrenergic receptor-induced lipolytic response. S-28-Y exhibited antagonist potencies toward ANPinduced lipolysis and behaved as a partial lipolytic agonist with a lower pD 2 value (7.4 Ϯ 0.2) than ANP (9.4 Ϯ 0.3). HS-142-1 exerted the weakest antagonistic effects. The results demonstrate that ANP-dependent effects do not interfere with ␤-and ␣ 2 -adrenergic pathways in human fat cells. They are unaffected by insulin pretreatments of fat cells but undergo desensitization. In the search of potent and specific natriuretic peptide receptor-A antagonist, in the human fat cell, A71915 was the only reliable one found.Natriuretic peptides ANP, BNP, and C-type natriuretic peptide (NPs) are a family of peptides that exert potent diuretic, natriuretic, and vasodilator activities (Athanassopoulos and Dennis, 1991; Levin et al., 1998). They are synthesized as preprohormones in the mammalian heart, stored as prohormones, and then released into the plasma after cardiomyocyte stretch. ANP sequence comprises 28 amino acids with a Cys 7 -Cys 23 bridge, which enables binding to atrial natriuretic peptide receptors (NPRs) (Levin et al., 1998). ANP binds with high affinity to human fat cell membranes, and we have recently demonstrated that NPs are potent lipolytic agents in human and in nonhuman primate fat cells only (Sengenes et al., 2000(Sengenes et al., , 2002a. Among the members of the NP family, the relative order of lipolytic potencies is ANP Ͼ BNP Ͼ C-type natriuretic peptide. The lipolytic activity of ANP and BNP is mediated by specific fat cell-plasma membrane receptors (NPR-A) bearing a guanylyl cyclase activity. They operate via a cGMP-dependent pathway and independently of phosphodiesterase-3B inhibition (Sengenes et al., 2000)....

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confidence: 99%

Functional and Pharmacological Characterization of the Natriuretic Peptide-Dependent Lipolytic Pathway in Human Fat Cells

Moro

Galitzky²,

Sengenès³

et al. 2003

J Pharmacol Exp Ther

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“…Adrenaline infusion increases ATBF and induces lipolysis through the b 2 -adrenoreceptors in adipose tissue [14]. Treatment with atenolol (a b 1 -blocker) reduced plasma NEFA concentrations after exercise in fed healthy volunteers, whereas doxazosin was without effect [15]. The technique of microdialysis has been used to study these interactions further.…”

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confidence: 99%

Effects of Acute Administration of Doxazosin on Fasting and Postprandial Haemodynamics and Lipid Metabolism in Healthy Subjects

Ulahannan

Karpe²,

Humphreys³

et al. 2002

Horm Metab Res

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The selective alpha1 -adrenoceptor antagonist doxazosin has apparently beneficial effects on insulin sensitivity and on plasma lipid concentrations. In order to understand these effects better, we investigated the acute effects of doxazosin on adipose tissue and forearm blood flow and on postprandial lipid metabolism in healthy subjects. Nine subjects were studied in a balanced, placebo-controlled design. Pulse rate, blood pressure, forearm and subcutaneous adipose tissue blood flow were measured before and for 6 h after a mixed meal, with concomitant measurements of blood metabolites and insulin. Doxazosin increased pulse rate (p = 0.02) and forearm blood flow (p < 0.01 in fasting state), and decreased vascular resistance in forearm (p < 0.05 for fasting values) and subcutaneous abdominal adipose tissue (p = 0.04). Fasting plasma non-esterified fatty acid concentrations were increased by 40 % (p < 0.05). No other metabolic effects were detected. The effects on adipose tissue vascular resistance and lipolysis (reflected in elevated non-esterified fatty acid concentrations) were unexpected, as these are usually considered to be mediated by the balance of alpha2 - and beta-adrenoceptor activity in humans. We conclude that alpha1 -adrenoceptor activity may be more important in regulation of human lipid metabolism than previously recognized.

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Effect of bisoprolol and atenolol on endurance exercise capacity in healthy men

Vanhees

Defoor

Schepers

et al. 2000

Journal of Hypertension

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Metabolic Effects of Atenolol and Doxazosin in Healthy Volunteers During Prolonged Physical Exercise

Cited by 4 publications

References 0 publications

Functional and Pharmacological Characterization of the Natriuretic Peptide-Dependent Lipolytic Pathway in Human Fat Cells

Functional and Pharmacological Characterization of the Natriuretic Peptide-Dependent Lipolytic Pathway in Human Fat Cells

Effects of Acute Administration of Doxazosin on Fasting and Postprandial Haemodynamics and Lipid Metabolism in Healthy Subjects

Effect of bisoprolol and atenolol on endurance exercise capacity in healthy men

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