Study of the hypothalamic angiotensin system in aortic coarctated rats using the reverse microdialysis technique.
The objective of our work was to study the intrahypothalamic actions of irbesartan, an angiotensin receptor antagonist, on blood pressure and dopaminergic and serotoninergic neurotransmission in sham operated (SO) and aortic coarctated (ACo) rats by using the microdialysis perfusion technique. We also studied a possible enhanced pressor response to angiotensin II in aortic coarctated rats in the anterior and posterior hypothalamic area. Wistar urethane-chloralose anaesthetised rats were used. A cannula was inserted in the carotid artery. A concentric microdialysis probe was implanted into the anterior hypothalamus or posterior hypothalamus and irbesartan (6 microg ml(-1)) was perfused through the probe. Changes of mean arterial pressure (MAP) were measured. 3,4-Dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in dialysate samples by HPLC-EC. A greater response to irbesartan perfusion in the anterior hypothalamic area of aortic coarctated rats was observed (SO rats, DMAP: -4.3+/-2.3 mm Hg; ACo rats, DMAP: -11.4+/-1.5 mm Hg, P<0.05). The pressor response to angiotensin II in the anterior hypothalamic area (SO rats, DMAP: 4.2+/-1.2 mm Hg; ACo rats, DMAP: 21.7+/-3.7 mm Hg, P<0.05) but not in the posterior hypothalamic area was enhanced in aortic coarctated rats. The perfusion of irbesartan in the anterior hypothalamic area did not modify the extracellular levels of 5-HIAA in both experimental groups, but induced a slightly reduction of DOPAC levels in sham operated rats. The results suggest that the angiotensin system in the anterior hypothalamic area is involved in the maintenance of hypertension in ACo rats and it appears that the increased pressor reactivity to angiotensin II is related to this enhanced function. On the other hand, the effect of irbesartan on DOPAC dialysate levels suggests that the drug produces an alteration of the dopaminergic neurotransmission in the SO rats.
Höcht
Christian
C
Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, (C1113AAD) Buenos Aires, Argentina. chocht@ffyb.uba.ar
Opezzo
Javier A W
JA
Gironacci
Mariela
M
Peña
Clara
C
Taira
Carlos A
CA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D001017:Aortic Coarctation / Q000503:physiopathology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007032:Hypothalamus, Anterior / Q000187:drug effects; D007034:Hypothalamus, Posterior / Q000187:drug effects; D000077405:Irbesartan; D008297:Male; D017551:Microdialysis / Q000379:methods; D010477:Perfusion / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000502:physiology*; D012701:Serotonin; D013777:Tetrazoles / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D015102:3,4-Dihydroxyphenylacetic Acid; D000804:Angiotensin II; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D000077405:Irbesartan