Role of the lateral tegmental field in the central sympatho-inhibitory effect of 8-hydroxy-2-(di-n-propylamino)tetralin in the cat.
Cardiovascular neurones with sympathetic nerve and cardiac related activity have been detected in the lateral tegmental field and have been classified depending on their response to baroreceptor activation. Baroreflex activation decreased and increased the firing rate of sympatho-excitatory neurones and sympatho-inhibitory neurones respectively. Intravenous (i.v.) administration of 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) (1 to 30 micrograms/kg) produced a dose-dependent decrease in the firing rate of sympatho-excitatory neurones in conjunction with a decrease in renal sympathetic nerve activity. 8-OH-DPAT had a variable effect (excitation or inhibition) on the firing rate of sympatho-inhibitory lateral tegmental field neurones. Both the excitatory and the inhibitory effects of 8-OH-DPAT were reversed by spiperone (1 mg/kg i.v.). Microinjection of 8-OH-DPAT (2 nmol/site) into the lateral tegmental field decreased blood pressure and renal sympathetic nerve activity. Compared with the effects elicited by microinjection of 8-OH-DPAT into the rostral ventrolateral medulla, the renal sympatho-inhibitory response elicited by 8-OH-DPAT injected into the lateral tegmental field appeared smaller. Chemical lesions of the lateral tegmental field neurones with kainic acid produced hypertension and sympatho-excitation. The correlation between renal sympathetic nerve activity and the R wave of the electrocardiogram disappeared after treatment with kainic acid. Subsequent i.v. 8-OH-DPAT (1 to 100 micrograms/kg) failed to alter blood pressure and renal sympathetic activity. In contrast clonidine (1 to 10 micrograms/kg) still decreased blood pressure, heart rate and renal sympathetic nerve activity in kainic acid-lesioned animals and these effects were reversed by the alpha 2-adrenoceptor antagonist, methoxy-idazoxan (10 micrograms/kg i.v.). The data described indicate that the lateral tegmental field plays a role in the central cardiovascular effects of 8-OH-DPAT and that the integrity of this area is necessary for the expression of the sympatho-inhibitory effects of the drug.
Vayssettes-Courchay
C
C
Servier Research Institute, Division of Angiology, Suresnes, France.
offysset
F
F
Verbeuren
T J
TJ
Laubie
M
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007608:Kainic Acid / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology; D008845:Microinjections; D009474:Neurons / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003000:Clonidine; D007608:Kainic Acid