Biomaterial Database

Glucocorticoids, sympathetic activity, and presynaptic alpha 2-adrenoceptor function in humans. 1995

J W Lenders, and A Golczynska, and D S Goldstein

Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.

The sympathetic nervous system and the pituitary-adrenocortical system are two of the body's main stress effector systems. Animal studies have indicated that exogenously administered glucocorticoids inhibit sympathetic outflows and interfere with the function of presynaptic alpha 2-adrenoceptors modulating neuronal norepinephrine (NE) release. The present study tested whether glucocorticoids produce similar effects in humans. In a randomized, double-blind, placebo-controlled cross-over experiment, 15 healthy subjects took 20 mg prednisone or placebo orally daily each morning for 1 week, followed by the other drug after a 1-week washout. On the last day of each treatment week, blood samples were drawn for assays of plasma levels of catechols and ACTH before and after iv infusion of the alpha 2-adrenoceptor antagonist yohimbine (YOH) (0.125 mg/kg bolus, 0.001 mg.kg-1.min-1 infusion). In 7 subjects, directly recorded peroneal skeletal muscle sympathetic nerve activity (MSNA) was also measured at baseline and after YOH infusion at the end of both treatment weeks. Prednisone decreased plasma NE levels and MSNA compared with levels after placebo (1.09 +/- 0.11 nmol/L vs. 1.40 +/- 0.13 nmol/L, P < 0.01; 30 +/- 4 bursts/min vs. 36 +/- 3 bursts/min, P < 0.05) without affecting blood pressure or pulse rate. YOH increased mean arterial blood pressure by 12% (P < 0.001) and heart rate by 7% (P < 0.05); prednisone did not alter these effects of YOH. YOH-induced proportionate increments in plasma NE levels averaged about 10 times those in MSNA. Prednisone did not affect the YOH-induced proportionate increments in plasma NE levels (placebo, 243%; prednisone, 237%) or MSNA (placebo, 22%; prednisone, 23%). The decrements in MSNA and plasma NE levels after prednisone treatment indicate that glucocorticoids inhibit sympathoneural outflows in humans. The 10-fold larger NE than MSNA response to YOH confirms substantial inhibitory modulation of NE release by alpha 2-adrenoceptors on noradrenergic terminals, and the similarity of responses to YOH after prednisone or placebo suggests that glucocorticoid-induced sympathoinhibition occurs independently of altered modulatory function of alpha 2-adrenoceptors on noradrenergic terminals.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008734	Methoxyhydroxyphenylglycol	Synthesized from endogenous epinephrine and norepinephrine in vivo. It is found in brain, blood, CSF, and urine, where its concentrations are used to measure catecholamine turnover.	Hydroxymethoxyphenylglycol,MHPG,MOPEG,Vanylglycol,4-Hydroxy-3-methoxyphenylethylene Glycol,4-Hydroxy-3-methoxyphenylethyleneglycol,4-Hydroxy-3-methoxyphenylglycol,Methoxyhydroxyphenylglycol, (+)-Isomer,Methoxyhydroxyphenylglycol, (+-)-Isomer,Methoxyhydroxyphenylglycol, (-)-Isomer,4 Hydroxy 3 methoxyphenylethylene Glycol,4 Hydroxy 3 methoxyphenylethyleneglycol,4 Hydroxy 3 methoxyphenylglycol
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009638	Norepinephrine	Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic.	Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010919	Placebos	Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol.	Sham Treatment
D011241	Prednisone	A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver.	Dehydrocortisone,delta-Cortisone,Apo-Prednisone,Cortan,Cortancyl,Cutason,Dacortin,Decortin,Decortisyl,Deltasone,Encorton,Encortone,Enkortolon,Kortancyl,Liquid Pred,Meticorten,Orasone,Panafcort,Panasol,Predni Tablinen,Prednidib,Predniment,Prednison Acsis,Prednison Galen,Prednison Hexal,Pronisone,Rectodelt,Sone,Sterapred,Ultracorten,Winpred,Acsis, Prednison
D011942	Receptors, Adrenergic, alpha	One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.	Adrenergic alpha-Receptor,Adrenergic alpha-Receptors,Receptors, alpha-Adrenergic,alpha-Adrenergic Receptor,alpha-Adrenergic Receptors,Receptor, Adrenergic, alpha,Adrenergic alpha Receptor,Adrenergic alpha Receptors,Receptor, alpha-Adrenergic,Receptors, alpha Adrenergic,alpha Adrenergic Receptor,alpha Adrenergic Receptors,alpha-Receptor, Adrenergic,alpha-Receptors, Adrenergic
D001794	Blood Pressure	PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.	Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D004311	Double-Blind Method	A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment.	Double-Masked Study,Double-Blind Study,Double-Masked Method,Double Blind Method,Double Blind Study,Double Masked Method,Double Masked Study,Double-Blind Methods,Double-Blind Studies,Double-Masked Methods,Double-Masked Studies,Method, Double-Blind,Method, Double-Masked,Methods, Double-Blind,Methods, Double-Masked,Studies, Double-Blind,Studies, Double-Masked,Study, Double-Blind,Study, Double-Masked
D005260	Female		Females