Chronic antioxidant treatment improves sympathetic functions and beta-adrenergic pathway in the spontaneously hypertensive rats.
BACKGROUND
Correlations have been found between oxidative stress and hypertension.


OBJECTIVE
To determine whether antioxidants can normalize sympathetic dysfunction at pre- or postsynaptic levels in spontaneously hypertensive rats (SHRs).


RESULTS
Untreated SHRs and Wistar-Kyoto (WKY) rats were compared with rats treated with melatonin (30 mg/kg per day) or N-acetylcysteine (NAC) (4 g/kg per day) given in drinking water for 4 weeks. At the presynaptic level, SHRs had greater plasma noradrenaline concentrations (P <0.01) and an enhanced release of [3H]noradrenaline from isolated atria (P <0.001). At the postsynaptic level, they exhibited an increased proportion of beta2-adrenoceptors in the heart (P <0.001)and a decrease in the chronotropic and mean arterial pressure (MAP) responses to isoproterenol (P <0.001). Melatonin and NAC decreased MAP (P <0.001) and heart rate (P <0.05), and restored the plasma noradrenaline concentrations (P<0.01 and P <0.001, respectively), the chronotropic response to isoproterenol (P <0.05) and the proportions of beta(1)/beta(2)-adrenoceptors in the heart (P <0.05) in SHRs to the levels found in WKY rats. The same treatments decreased the release of [3H]noradrenaline from isolated atria (P <0.05), and melatonin slightly improved the relaxation in the aorta in SHRs only (P <0.05). Plasma concentrations of adrenaline, the isoproterenol-induced relaxation in mesenteric arteries, the total density and affinity of beta-adrenoceptors in the heart, and the adenylate cyclase reactivity of cardiac membranes to isoproterenol, forskolin, sodium fluoride and guanylylimidophosphate were not altered by the treatments.


CONCLUSIONS
These results suggest that NAC and melatonin decreased the MAP and heart rate and improved the chronotropic response to isoproterenol in SHRs, in association with an inhibition of sympathetic activity and the restoration of cardiac beta-adrenoceptor function.
Girouard
Hélène
H
Research Group on Autonomic Nervous System, Department of Physiology, Faculty of Medicine, University of Montréal, Montréal, Québec, Canada, H3C 3J7.
Chulak
Chantal
C
LeJossec
Mireille
M
Lamontagne
Daniel
D
de Champlain
Jacques
J
D000111:Acetylcysteine / Q000008:administration & dosage*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001011:Aorta / Q000187:drug effects; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D004334:Drug Administration Schedule; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D008638:Mesenteric Arteries / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*
D000318:Adrenergic beta-Agonists; D000975:Antioxidants; D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases; D008550:Melatonin; D007545:Isoproterenol; D000111:Acetylcysteine