Anterior hypothalamic beta-adrenoceptors in chronic aortic-coarctated hypertensive rats: an interaction with central angiotensin II receptors.
1. The aim of the present study was to investigate the activity of anterior hypothalamic beta-adrenoceptors and angiotensin (Ang) II receptors on blood pressure in normotensive rats and aortic-coarctated (ACo) animals at a chronic stage of hypertension. A possible interaction between beta-adrenoceptors and AngII pressor activity was also investigated. 2. Injection of isoproterenol (0.1-10 nmol) in the anterior hypothalamic area induced a dose-dependent decrease in mean arterial pressure (MAP) in sham-operated (SO), but not in ACo, animals. Isoproterenol (1 nmol) reduced blood pressure in SO rats (DeltaMAP -10.1+/-1.4 mmHg; n=10) but not in ACo animals (DeltaMAP -0.9+/-1.6 mmHg; n=10; P<0.05 vs SO rats). Whereas previous administration of atenolol (40 nmol) enhanced the cardiovascular effect of isoproterenol (1 nmol) in ACo rats but not in SO animals, propranolol (40 nmol) prevented the hypotensive action of isoproterenol in both experimental groups. Intrahypothalamic administration of clenbuterol decreased MAP in a dose-dependent manner; however, the depressor response to clenbuterol (10 nmol) was greater in ACo rats than in SO rats (DeltaMAP -26.8+/-3.2 vs -14.4+/-2.4 mmHg, respectively; n=5 for both; P<0.05). When AngII (50 ng) was injected into the anterior hypothalamic area, a greater pressor response was observed in ACo rats than in SO rats (DeltaMAP 19.6+/-1.1 vs 11.3+/-0.6 mmHg, respectively; n=5 for both; P<0.05). Atenolol (40 nmol) pretreatment partially and significantly prevented the pressor response to AngII in ACo rats, but not in SO rats. 3. In conclusion, these results provide pharmacological evidence for the existence of a beta1-adrenoceptor-mediated pressor mechanism in the anterior hypothalamic area of ACo rats that is absent in SO rats. The enhanced depressor beta2-adrenoceptor activity observed in chronic ACo rats could be a compensatory adjustment to pressor beta1-adrenoceptor activity. Conversely, pressor overactivity of AngII was observed in the anterior hypothalamic area of ACo rats at a chronic hypertensive stage; this enhancement could be explained, at least in part, by the pressor beta1-adrenoceptor activity.
Höcht
Christian
C
Departamento de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina. chocht@ffyb.uba.ar
Opezzo
Javier A W
JA
Gironacci
Mariela M
MM
Peña
Clara
C
Taira
Carlos A
CA
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D007025:Anterior Hypothalamic Nucleus / Q000378:metabolism*; D001017:Aortic Coarctation / Q000150:complications / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002908:Chronic Disease; D002976:Clenbuterol / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000150:complications / Q000378:metabolism*; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D008845:Microinjections; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D007545:Isoproterenol; D002976:Clenbuterol