Evidence for an antagonistic angiotensin II/alpha 2-adrenoceptor interaction in the nucleus tractus solitarii.
Interactions between alpha 2-adrenoceptors and angiotensin II receptors were evaluated in the nucleus tractus solitarii of the rat by means of quantitative receptor autoradiography and cardiovascular analysis. In binding experiments using l-noradrenaline to compete for [3H]p-aminoclonidine binding sites, angiotensin II (1 nM) increased the IC50 value of l-noradrenaline by 50%. The angiotensin AT1 receptor antagonist, DUP753 (losartan), not only blocked this action but also decreased the IC50 value of l-noradrenaline. The modulatory effect of angiotensin II was also evaluated after addition of both DUP753 and PD123319, an angiotensin AT2 receptor antagonist, and counteraction of the reduction in the IC50 value of l-noradrenaline was observed. In saturation experiments angiotensin II increased the KD and Bmax values of [3H]p-aminoclonidine binding sites, compatible with possible uncoupling of the alpha 2-adrenoceptors. Cardiovascular analysis demonstrated that a threshold dose of angiotensin II (0.05 pmol) counteracted the vasodepressor effect produced by an ED50 dose of l-adrenaline, l-noradrenaline or clonidine coinjected in the nucleus tractus solitarii. DUP753 fully blocked this in vivo modulation of alpha 2-adrenoceptors by angiotensin II. These findings suggest the existence of an antagonistic angiotensin AT1/alpha 2-adrenoceptor interaction in the nucleus tractus solitarii. Therefore, it can be surmised that the activation of angiotensin II AT1 receptors may reduce the transduction of the alpha 2-adrenoceptors and thus the alpha 2-mediated vasodepressor responses.
Fior
D R
DR
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Yang
S N
SN
Hedlund
P B
PB
Narváez
J A
JA
Agnati
L F
LF
Fuxe
K
K
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000805:Angiotensin III / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D019808:Losartan; D008297:Male; D008845:Microinjections; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D011945:Receptors, Angiotensin / Q000378:metabolism; D012984:Software; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D018341:Receptors, Adrenergic, alpha-2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D000805:Angiotensin III; C073402:PD 123319; C016986:apraclonidine; D019808:Losartan; D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine