Interaction between beta-adrenergic receptor stimulation and nitric oxide release on tissue perfusion and metabolism.
Nitric oxide (NO) may be an important modulator of sympathetic tone. We used im and sc microdialysis in humans to characterize the interaction of NO synthase inhibition and adrenoreceptor stimulation on tissue perfusion, metabolism, and norepinephrine release. Microdialysis probes were perfused with L- or D-nitro-L-arginine-methyl-ester (100 micromol/L) followed by incremental doses of isoproterenol, epinephrine, or nitroprusside. Blood flow was estimated based on the ethanol dilution technique. In muscle, the increase in blood flow with isoproterenol was abolished by L-NAME. The ethanol ratio was 0.03 +/- 0.011 with D-NAME and 0.075 +/- 0.014 with L-NAME during isoproterenol treatment (1 micromol/L). The effect was less pronounced in adipose tissue. The vasodilatory effect of nitroprusside was similar with D- and L-NAME. L-NAME augmented isoproterenol- and epinephrine-induced glycerol release. Dialysate glycerol during 1 micromol/L isoproterenol was 47 +/- 6.7 micromol/L with D-NAME and 72 +/- 15 micromol/L with L-NAME. In skeletal muscle, dialysate norepinephrine during 1 micromol/L isoproterenol treatment was 0.73 +/- 0.17 and 1.3 +/- 0.15 nmol/L with D- and L-NAME, respectively. We conclude that NO synthase inhibition attenuates beta(2)-adrenoreceptor-mediated vasodilation and enhances beta-adrenoreceptor-mediated lipolysis. These effects are in part mediated through an increase in interstitial norepinephrine concentrations. The data are consistent with the idea that in humans, NO is important in modulating and ameliorating sympathetic effects in peripheral tissues.
Jordan
J
J
Clinical Research Center, Franz Volhard Clinic, Max Delbrück Center, Medical Faculty of the Charité, Humboldt University, 13125 Berlin, Germany. jordan@fvk-berlin.de
Tank
J
J
Stoffels
M
M
Franke
G
G
Christensen
N J
NJ
Luft
F C
FC
Boschmann
M
M
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D001775:Blood Circulation / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester; D004837:Epinephrine