Anterior hypothalamic beta-adrenergic activity in the maintenance of hypertension in aortic coarctated rats.
The aim of this work was to demonstrate an alteration of the anterior hypothalamic catecholaminergic system in aortic coarctated (ACo) rats by the perfusion of beta-adrenergic antagonist and the microinfusion of beta-adrenergic agonist. Wistar urethane-chloralose anesthetized rats were used. The carotid artery was cannulated for blood pressure recording and changes in blood pressure were measured. A concentric microdialysis probe was inserted in the anterior hypothalamus. Metoprolol (a beta(1)-adrenoceptor antagonist) perfusion (6 microg ml(-1)) reduced the mean arterial pressure (MAP) in the ACo rats but not in sham operated (SO) animals. The anterior hypothalamic infusion of non-specific beta-adrenergic agonist isoproterenol induced a dose-dependent decrease of blood pressure in both experimental groups, but the depressor response was significantly lower in ACo rats. The pretreatment with atenolol, a selective beta(1)-adrenoceptor antagonist, increased the depressor effect of isoproterenol in ACo rats, but not in SO rats. On the other hand, the hypotensive action of isoproterenol was significantly diminished after the administration of non-specific beta-adrenoceptor antagonist propranolol in SO and ACo rats. The anterior hypothalamic infusion of clenbuterol, a selective beta(2)-adrenergic agonist, induced a dose-dependent decrease of blood pressure in both experimental groups. The depressor response to clenbuterol (1 nmol) was significantly lower in ACo rats than in SO rats. In summary, this study provides the evidence that there is a beta(1)-adrenergic compromise in anaesthetized ACo rats and this compromise may be involved in the maintenance of hypertension. On the other hand, this study also suggests the existence of pressor beta(1)-adrenoceptors in the anterior hypothalamic area of ACo rats but not in SO rats. We also found a diminished depressor beta(2)-adrenergic activity in ACo rats.
Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, (C1113AAD) Buenos Aires, Argentina. chocht@ffyb.uba.ar
Christian
C
Höcht
Javier A W
JA
Opezzo
Carlos A
CA
Taira
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D007025:Anterior Hypothalamic Nucleus / Q000187:drug effects* / Q000503:physiopathology; D001017:Aortic Coarctation / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D001262:Atenolol / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002976:Clenbuterol / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D007022:Hypotension / Q000139:chemically induced; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D008845:Microinjections / Q000379:methods; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D001262:Atenolol; D011433:Propranolol; D008790:Metoprolol; D007545:Isoproterenol; D002976:Clenbuterol