Effects of clonidine on renal sympathetic nerve activity and norepinephrine spillover.
The antihypertensive action of clonidine (CLO) depends mainly on decreased release of the sympathetic neurotransmitter, norepinephrine (NE), at vascular neuroeffector junctions. The decreased release can be due to stimulation of alpha-2 adrenoceptors or other receptors in the brain or due to stimulation of presynaptic inhibitory alpha-2 adrenoceptors on sympathetic nerve endings. To compare central and peripheral contributions to the depressor action of CLO, renal sympathetic nerve activity (RSNA) and renal spillover of NE (RNEs) were measured at baseline and during reflexive increases in RSNA evoked by nitroprusside-induced hypotension (27, 50 and 105 micrograms/kg/min) before and after CLO treatment in adrenal-demedullated, anesthetized rats. Administration of CLO decreased RSNA by 52 +/- 8% and RNEs by 32 +/- 13% (means +/- S.E.M.). At levels of RSNA less than 50% above control, there were no significant changes in RNEs; above this level of activity RNEs increased, regardless of CLO treatment. CLO treatment did not alter significantly the relationship between increases in RSNA and in RNEs during nitroprusside-induced hypotension. The results suggest that in neurologically intact, anesthetized animals, CLO decreases renal NE release mainly by inhibiting sympathetic outflow, with little if any peripheral presynaptic action.
Garty
M
M
Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.
Deka-Starosta
A
A
Chang
P
P
Kopin
I J
IJ
Goldstein
D S
DS
D000313:Adrenal Medulla / Q000601:surgery; D000818:Animals; D002395:Catecholamines / Q000097:blood; D003000:Clonidine / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced / Q000378:metabolism; D007668:Kidney / Q000294:innervation*; D008297:Male; D009599:Nitroprusside / Q000009:adverse effects; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
D002395:Catecholamines; D009599:Nitroprusside; D003000:Clonidine; D009638:Norepinephrine