title: Increased sympathetic activity in rats submitted to chronic intermittent hypoxia.
abstract: Long-term exposure to intermittent hypoxia may lead to important cardiovascular dysfunctions, such as hypertension. Rodent models of chronic intermittent hypoxia (CIH) have been used to study the mechanisms underlying the increase in mean arterial pressure (MAP) observed after exposure to CIH. Several studies suggest that the hypertension of rats submitted to CIH is associated with an increase in sympathetic activity. However, there are no studies documenting the direct measurement of sympathetic activity in conscious freely moving rats exposed to CIH. Therefore, the present study aimed to evaluate whether or not the increase of MAP in rats exposed to CIH is associated with an increase in sympathetic activity. To reach this goal, we analysed the effect of ganglionic blockade on baseline MAP as well as the plasma levels of catecholamines. Rats submitted to CIH (fractional inspired O(2) of 6%, for 40 s in every 9 min, 8 h day(-1)) for 35 days (n = 31) exhibited a significant increase in MAP compared with control rats (n = 28) maintained under normoxia (112 +/- 2 versus 103 +/- 1 mmHg, P = 0.0003). The injection of the ganglionic blocker hexamethonium resulted in a similar fall in MAP in CIH and control groups (-46 +/- 2 versus -41 +/- 3 mmHg). However, hexamethonium after previous antagonism of the angiotensin II type 1 (AT(1)) receptors with losartan produced a larger decrease in MAP in the CIH than in the control group (-58 +/- 2 versus -50 +/- 2 mmHg, P = 0.0165). The injection of losartan itself produced no major changes in the baseline MAP in both groups. The measurement of plasma catecholamines showed an increase in plasma noradrenaline (10.12 +/- 0.90 versus 4.74 +/- 0.32 ng ml(-1), P = 0.0042) in rats exposed to CIH compared with control rats. These data provide strong evidence to support the concept that rats submitted to CIH exhibit an increase in sympathetic activity, which seems to be determinant in the maintenance of hypertension in this experimental model.
authors.affiliation: Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Zoccal
authors.forename: Leni G H
authors.initials: LG
authors.lastname: Bonagamba
authors.forename: Fabíola R T
authors.initials: FR
authors.lastname: Oliveira
authors.forename: José
authors.initials: J
authors.lastname: Antunes-Rodrigues
authors.forename: Benedito H
authors.initials: BH
authors.lastname: Machado
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D004195:Disease Models, Animal; D004837:Epinephrine / Q000097:blood; D005728:Ganglia, Sympathetic / Q000503:physiopathology; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate; D018738:Hexamethonium / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D005730:Ganglionic Blockers; D018738:Hexamethonium; D019808:Losartan; D009638:Norepinephrine; D004837:Epinephrine