atrial-natriuretic-factor and tertatolol

Involvement of sympathetic nervous system and natriuretic peptides in the control of exercise-induced lipid mobilization was compared in overweight and lean men. Lipid mobilization was determined using local microdialysis during exercise. Subjects performed 35-min exercise bouts at 60% of their maximal oxygen consumption under placebo or after oral tertatolol [a beta-adrenergic receptor (AR) antagonist]. Under placebo, exercise increased dialysate glycerol concentration (DGC) in both groups. Phentolamine (alpha-AR antagonist) potentiated exercise-induced lipolysis in overweight but not in lean subjects; the alpha(2)-antilipolytic effect was only functional in overweight men. After tertatolol administration, the DGC increased similarly during exercise no matter which was used probe in both groups. Compared with the control probe under placebo, lipolysis was reduced in lean but not in overweight men treated with the beta-AR blocker. Tertatolol reduced plasma nonesterified fatty acids and insulin concentration in both groups at rest. Under placebo or tertatolol, the exercise-induced changes in plasma nonesterified fatty acids, glycerol, and insulin concentrations were similar in both groups. Exercise promoted a higher increase in catecholamine and ANP plasma levels after tertatolol administration. In conclusion, the major finding of our study is that in overweight men, in addition to an increased alpha(2)-antilipolytic effect, the lipid mobilization in subcutaneous adipose tissue that persists during exercise under beta-blockade is not dependent on catecholamine action. On the basis of correlation findings, it seems to be related to a concomitant exercise-induced rise in plasma ANP when exercise is performed under tertatolol intake and a decrease in plasma insulin.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Adult; Atrial Natriuretic Factor; Blood Glucose; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Exercise; Glycerol; Humans; Insulin; Lipid Mobilization; Male; Overweight; Phentolamine; Propanolamines; Subcutaneous Fat; Thiophenes

In humans, lipid mobilization is considered to depend mainly on sympathetic nervous system activation and catecholamine action. A contribution of ANP was hypothesized because we have previously shown that atrial natriuretic peptide (ANP) is a lipolytic agent on isolated human fat cells. Control of lipid-mobilizing mechanisms was investigated using in situ microdialysis in subcutaneous adipose tissue (SCAT) in healthy young men during two successive exercise bouts performed at 35% and 60% peak oxygen consumption (VO2max) after placebo or acute oral tertatolol (nonselective beta-antagonist) treatment. In placebo-treated subjects, infusion of propranolol in the probe (100 micromol/l) only partially reduced (40%) the increment in extracellular glycerol concentration (EGC) promoted by exercise. Moreover, oral beta-adrenergic receptor blockade did not prevent exercise-induced lipid mobilization in SCAT while exerting fat cell beta-adrenergic receptor blockade. Exercise-induced increase in plasma ANP was potently amplified by oral tertatolol. A positive correlation was found between EGC and plasma ANP levels but also between extracellular cGMP (i.e., index of ANP-mediated lipolysis) and EGC. Thus, we demonstrate that exercise-induced lipid mobilization resistant to local propranolol and lipid-mobilizing action observed under oral beta-blockade is related to the action of ANP. Oral beta-adrenergic receptor blockade, which potentiates exercise-induced ANP release by the heart, may contribute to lipid mobilization in SCAT. The potential relevance of an ANP-related lipid-mobilizing pathway is discussed.

Topics: Adipocytes; Adipose Tissue; Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Adult; Atrial Natriuretic Factor; Blood Glucose; Cross-Over Studies; Cyclic GMP; Double-Blind Method; Epinephrine; Exercise; Exercise Test; Extracellular Fluid; Fatty Acids, Nonesterified; Glycerol; Guanylate Cyclase; Humans; Isoproterenol; Lipolysis; Male; Microdialysis; Norepinephrine; Oxygen Consumption; Phentolamine; Propanolamines; Propranolol; Receptors, Adrenergic, beta; Receptors, Atrial Natriuretic Factor; Subcutaneous Tissue; Sympathetic Nervous System; Thiophenes

To evaluate the contribution of atrial distension and/or adrenergic mechanisms in the regulation of atrial natriuretic peptide (ANP) secretion, plasma immunoreactive ANP, norepinephrine (NE), epinephrine (E), and left atrial diameter were measured at rest, during, and after graded upright standardised bicycle exercise in 8 healthy male subjects after single-dose administration of placebo, tertatolol (5 mg), prazosin (1 mg), or combination of tertatolol (5 mg) and prazosin (1 mg). Systolic and diastolic left atrial diameters were measured before, during, and just after exercise by bidimensional echocardiography. Exercise raised plasma ANP concentrations. This rise was greater on tertatolol alone and tertatolol and prazosin than on placebo or prazosin alone: mean area under the plasma ANP concentration curve increased by 35% on tertatolol alone, 45% on tertatolol and prazosin when compared with placebo (p < 0.01), and by 82 and 94%, respectively, when compared with prazosin alone (p < 0.01). The rise in plasma ANP was greater during the postexercise period: 80% for tertatolol alone, 67% for tertatolol and prazosin when compared with placebo (p < 0.01) and 133 and 115%, respectively, when compared with prazosin alone (p < 0.01). The rise in plasma ANP was accompanied by an increase in both systolic and diastolic atrial diameters which was significantly greater on tertatolol alone and on the tertatolol and prazosin combination than on placebo or prazosin alone (p < 0.001). Beta-blockade alone did not affect plasma catecholamine concentrations but exercise-induced increase in plasma NE was significantly potentiated by prazosin and the prazosin and tertatolol combination, and that of plasma E by the prazosin and tertatolol combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenergic beta-Antagonists; Adult; Atrial Function, Left; Atrial Natriuretic Factor; Double-Blind Method; Echocardiography; Epinephrine; Exercise; Exercise Test; Heart Atria; Humans; Male; Myocardial Contraction; Norepinephrine; Prazosin; Propanolamines; Receptors, Adrenergic, alpha; Receptors, Adrenergic, beta; Thiophenes

The role of atrial distension and/or adrenergic mechanisms in the regulation of atrial natriuretic peptide (ANP) secretion, plasma immunoreactive ANP, norepinephrine (NE), epinephrine (E) and left atrial diameter at rest, during and after graded bicycle exercise has been studies in 8 healthy male subjects after single doses of placebo, tertatolol 5 mg (a non-selective beta-adrenoceptor blocker), prazosin 1 mg (an alpha 1-adrenoceptor antagonist) and their combination. Systolic and diastolic left atrial diameters were measured before, during and just after exercise by bidimensional echocardiography. Exercise caused an increase in plasma ANP, which was greater after tertatolol alone, and tertatolol plus prazosin, than after placebo or prazosin alone; the mean area under the plasma ANP concentration curve was increased by 35% after tertatolol alone, by 45% after tertatolol and prazosin compared to placebo, and by 82% and 94%, respectively when compared to prazosin alone. The rise in plasma ANP was more marked during the post-exercise period: 80% after tertatolol alone, 67% after tertatolol and prazosin compared to placebo, and 133% and 115%, respectively, compared to prazosin alone. The rise in plasma ANP was accompanied by an increase in both the systolic and diastolic atrial diameter, which was also significantly greater after tertatolol alone and the combination than placebo, or after prazosin alone. beta-Adrenoceptor blockade alone did not affect the plasma catecholamine concentrations, but the exercise-induced increase in plasma norepinephrine was significantly potentiated by prazosin and by prazosin plus tertatolol, and that of plasma epinephrine by the drug combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenergic beta-Antagonists; Adult; Atrial Function; Atrial Natriuretic Factor; Blood Pressure; Double-Blind Method; Echocardiography; Epinephrine; Exercise; Heart Atria; Humans; Male; Norepinephrine; Prazosin; Propanolamines; Thiophenes

The effect of a non selective and a cardio-selective beta-blocker on basal and exercise-stimulated plasma atrial natriuretic peptide concentrations in healthy volunteers has been studied. Nine healthy volunteers received single oral doses of 5 mg tertatolol, 100 mg atenolol or placebo, at one week intervals, in a double blind cross over trial. At rest plasma atrial natriuretic peptide, aldosterone, antidiuretic hormone and cyclic GMP concentrations and plasma renin activity were not modified by the treatments. During exercise plasma atrial natriuretic peptide concentrations were significantly increased by each treatment, the increment being significantly greater on beta-blockers than on placebo. The rise in atrial natriuretic peptide was 72% after placebo (from 24 to 42 pg/ml), 184% after atenolol (from 30 to 86 pg/ml), and 183% after tertatolol (from 34 to 95 pg/ml), respectively. Thus, the study has shown that in healthy subjects the plasma natriuretic peptide concentration is increased by exercise and that the increase is considerably and equally potentiated by selective and non selective beta-adrenoceptor blockade. The effect may be mainly due to a reduction in ventricular contractility with an increase in atrial pressure. The beta-blockers did not influence the resting plasma atrial natriuretic peptide levels, which suggests that in healthy subjects basal atrial natriuretic peptide secretion is not controlled via beta-receptors.

Topics: Adrenergic beta-Antagonists; Adult; Atenolol; Atrial Natriuretic Factor; Double-Blind Method; Exercise; Humans; Male; Propanolamines; Thiophenes

Left kidneys obtained from male Wistar rats were perfused with Tyrode solution; the perfusion pressure was measured continuously and taken as an index of vascular resistance in the kidneys. 5-Hydroxytryptamine (5-HT; 3-50 nmol) caused dose-dependent dilator responses in kidneys preconstricted with noradrenaline (0.6 microM) and pretreated with ritanserin (10 nM) and ICS 205930 (10 nM). The 5-HT1 agonist 5-carboxamidotryptamine (5-CT; 16-64 nmol) also caused renal dilatations under similar conditions. The dilator responses to both 5-HT and 5-CT were antagonized by the non-selective 5-HT receptor antagonist metergoline (0.2 microM) and by the selective 5-HT1A receptor antagonist BMY 7378 (0.4 microM). The guanylate cyclase inhibitor methylene blue (30 microM) and the nitric oxide (NO) synthase inhibitor nitro-L-arginine (L-NNA; 100 microM) significantly attenuated the dilator responses to 5-HT and 5-CT. The 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.5-16 nmol) also caused dose-dependent dilator responses in preconstricted rat kidneys. These responses were antagonized by metergoline and BMY 7378 and significantly attenuated by the NO inhibitors hemoglobin (10 microM) and L-NNA. The renal dilator responses noted with the beta-adrenoceptor blocker tertatolol (1-32 nmol) were also antagonized by metergoline and BMY 7378 and significantly reduced by L-NNA and hemoglobin. Both 8-OH-DPAT and tertatolol (1-30 microM) significantly reduced the vasoconstrictor responses to angiotensin II (20 pmol). Our data indicate that 5-HT receptors located on the vascular endothelium of the renal circulation are involved in the dilator actions of 5-HT, 5-CT, 8-OH-DPAT and tertatolol, and suggest that these receptors resemble the 5-HT1A subtype.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Acetylcholine; Angiotensin II; Animals; Atrial Natriuretic Factor; Endothelium, Vascular; Kidney; Male; Nitroglycerin; Papaverine; Piperazines; Propanolamines; Rats; Rats, Inbred Strains; Receptors, Serotonin; Serotonin; Tetrahydronaphthalenes; Thiophenes; Vasodilation

The aim of the studies summarized in the present review was to obtain a pharmacological characterization of the in vitro renal vasodilator action of tertatolol. In isolated Tyrode-perfused rat kidneys, previously constricted with norepinephrine, serotonin or BaCl2, tertatolol evokes vasodilatation. These dilator responses cannot be explained by an interaction of tertatolol with alpha- or beta-adrenoceptors, muscarinic or nicotinic receptors, opioid receptors, dopamine receptors or histamine receptors, and they occur independently of the release of prostaglandins. Since methylene blue, an inhibitor of the soluble form of guanylate cyclase, reduces the renal dilator effect of tertatolol, this action could ultimately depend, at least in part, on the production of cyclic guanosine monophosphate; in this respect, the renal effects of tertatolol and atrial natriuretic factor (ANF) are different. From experiments performed with canine renal arteries and with the perfused rat mesentery, it can be concluded that the effect of tertatolol is more pronounced at the level of the resistance vessels. The in vitro renal dilator response observed with tertatolol may help to explain the beneficial effect on the renal circulation observed in both humans and experimental animals treated with the compound.

Topics: Adrenergic beta-Antagonists; Animals; Anti-Arrhythmia Agents; Atrial Natriuretic Factor; Cyclic GMP; Dogs; Endothelium, Vascular; Kidney; Microcirculation; Propanolamines; Rats; Renal Circulation; Thiophenes; Vasodilation