Effect of centrally acting alpha-adrenergic agonists on sympathetic nervous system function in humans.
Three studies were undertaken to reevaluate whether there is a peripheral component in the reduction of sympathetic activity caused by centrally acting drugs; and whether the antihypertensive effect of these drugs is due entirely to this reduction. Plasma growth hormone and norepinephrine concentrations were used as respective markers of central alpha-adrenoceptor stimulation and peripheral sympathetic activity. In six normal volunteers, intravenous infusion of 0.2 mg clonidine and 2 mg guanfacine was compared. The falls in systolic blood pressure and plasma norepinephrine concentration were slightly greater after clonidine (18 mm Hg and 0.22 ng/ml) than after guanfacine (12 mm Hg and 0.13 ng/ml) administration. These falls occurred earlier than the rise in growth hormone, which rose to a maximum of 23 and 20 IU/ml respectively at 45 minutes after dosing. In six patients with essential hypertension clonidine and alpha-methyldopa caused similar falls in blood pressure and plasma norepinephrine concentration although these changes occurred later with alpha-methyldopa. Plasma growth hormone levels remained undetectable in most patients. In Wistar rats the effect of central and peripheral alpha 2-blockade on clonidine-induced changes was compared. Two groups of six rats received intravenous RX 781094, 0.3 mg/kg, or vehicle 10 minutes before receiving clonidine, 5 micrograms/kg i.v. In the latter, control group, clonidine reduced mean blood pressure by 30.7 +/- 1.9 mm Hg and heart rate by 46 +/- 6.7 beats/min. Plasma norepinephrine fell from 0.22 +/- 0.023 ng/ml to 0.116 +/- 0.013 ng/ml. After pretreatment with RX 781094, blood pressure did not change and heart rate fell by 18 +/- 2.7 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D013006:Growth Hormone / Q000097:blood; D016316:Guanfacine; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D019329:Idazoxan; D008297:Male; D008750:Methyldopa / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D010648:Phenylacetates / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D006146:Guanidines; D010648:Phenylacetates; D016316:Guanfacine; D008750:Methyldopa; D013006:Growth Hormone; D003000:Clonidine; D009638:Norepinephrine; D019329:Idazoxan