Beneficial attenuating effect of L-threo-3,4-dihydroxyphenylserine on postural hypotension in anesthetized rats.
The effects of L-threo-DOPS (L-threo-3,4-dihydroxyphenylserine), a non-physiologic precursor amino acid of the natural form of norepinephrine, on postural hypotension were assessed in anesthetized rats. Rats were pretreated with DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine), a norepinephrine-decreasing agent acting on central and peripheral tissues, or hexamethonium, a ganglion-blocking agent. Postural hypotension was induced by 60 degrees head-up tilt for 4 min. L-Threo-DOPS (1-10 mg/kg, i.v.) produced an increase in basal blood pressure and attenuation of the postural hypotension, which persisted in a dose-related manner in rats pretreated with DSP-4 (50 mg/kg, i.p. 24 h prior to the tilt-experiment). Hexamethonium (5 mg/kg, i.v.)-induced postural hypotension was also attenuated dose-dependently by i.p. (3-30 mg/kg)- or p.o. (30 and 100 mg/kg)-administered L-threo-DOPS, associated with an increase in basal blood pressure. Neither attenuation of postural hypotension nor increase in basal blood pressure was observed after L-threo-DOPS (30 mg/kg i.p.) in rats pre-injected with carbidopa (20 mg/kg i.v.), a peripheral aromatic L-amino acid decarboxylase inhibitor, under the hexamethonium pretreatment. The effects of L-threo-DOPS administered by cumulative i.v. infusion (12.5-50 micrograms/kg/min) on the pressor responses to either spinal sympathetic nerve stimulation (1-10 Hz) or i.v. bolus-injected tyramine were also examined. L-Threo-DOPS dose-relatedly potentiated the pressor response to nerve stimulation in rats either untreated or pretreated with DSP-4 and the pressor response to tyramine in rats pretreated with DSP-4.(ABSTRACT TRUNCATED AT 250 WORDS)
Satoh
S
S
Department of Pharmacology, Tohoku University, Miyagi, Japan.
Oyabe
A
A
Tanno
M
M
Suzuki-Kusaba
M
M
D000758:Anesthesia; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D015103:Droxidopa / Q000494:pharmacology*; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011187:Posture; D051381:Rats; D011919:Rats, Inbred Strains; D012694:Serine; D013564:Sympathetic Nervous System / Q000187:drug effects; D014439:Tyramine / Q000494:pharmacology
D001596:Benzylamines; D006584:Hexamethonium Compounds; D010656:Phenylephrine; D012694:Serine; D015103:Droxidopa; C012102:DSP 4; D014439:Tyramine