Responsiveness of noradrenergic neurons in rat experimental hypertension.
We investigated possible abnormalities of cholinergic-noradrenergic neurotransmission in superior cervical ganglia in vitro in spontaneously hypertensive, Dahl salt-sensitive and deoxycorticosterone-salt-hypertensive rats by measuring the de novo synthesis of catecholamines from their labeled precursor tritiated tyrosine in response to cholinergic stimulation. Labeled tyrosine was incorporated into dopamine and its main neuronal metabolite dihydroxyphenylacetic acid as well as into norepinephrine. Dihydroxyphenylacetic acid and norepinephrine, but not dopamine, generation was linear with time under basal and stimulated conditions. However, norepinephrine incorporation remained similar before and after cholinergic stimulation of ganglionic neurons. Only young, prehypertensive spontaneously hypertensive rats showed altered responses when compared with their controls. Although endogenous dihydroxyphenylacetic acid content and baseline tyrosine incorporation into dihydroxyphenylacetic acid were lower in 4-week-old spontaneously hypertensive rats than in age-matched Wistar-Kyoto rats, cholinergic stimulation increased labeled dopamine and dihydroxyphenylacetic acid generation significantly more in juvenile spontaneously hypertensive rats. Such a hyperresponsiveness was not observed in either young Dahl rats or in any of the other models when they became hypertensive. These results probably reflect a genuine hyperreactivity of postganglionic noradrenergic neurons to acetylcholine or their increased catecholamine-synthesizing ability after centrally evoked enhanced sympathetic outflow known to occur during the early development of hypertension in spontaneously hypertensive rats.
Debinski
W K
WK
Clinical Research Institute of Montreal, Quebec, Canada.
Kuchel
O G
OG
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002395:Catecholamines / Q000096:biosynthesis; D004351:Drug Resistance; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D010277:Parasympathomimetics / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D012965:Sodium Chloride / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism
D002395:Catecholamines; D010277:Parasympathomimetics; D014443:Tyrosine; D012965:Sodium Chloride; D002217:Carbachol; D009638:Norepinephrine