cyclic-gmp and tertatolol

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

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