Received August 18, 2006
Revised September 20, 2006
Accepted after revision October 26, 2006

¹ University of São Paulo

^* To whom correspondence should be addressed. E-mail: bhmachad{at}fmrp.usp.br.

	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 CIH exposure. 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 CIH rats. Therefore, the present study aimed to evaluate whether or not the increase of MAP in CIH rats is associated with an increase in sympathetic activity. To reach this goal, we analyzed the effect of the ganglionic blockade on baseline MAP as well as the plasma levels of catecholamines. Rats submitted to CIH (FiO2 of 6%, for 40 seconds, every 9 min, 8 hours/day) for 35 days (n=31) presented a significant increase in MAP compared to control rats (n=28) maintained under normoxia (112±2 vs 103±1 mmHg, P=0.0003). The injection of the ganglionic blocker hexamethonium in specific group of rats produced similar fall in MAP in CIH and control rats (-46±2 vs -41±3 mmHg). However, hexamethonium after previous antagonism of AT1 receptor losartan, produced a larger decrease in MAP of CIH than in control group (-58±2 vs -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 norepinephrine (10.12±0.90 vs 4.74±0.32 ng/mL, P=0.0042) in CIH rats compared to control rats. These data provide strong evidence to support the concept that rats submitted to CIH present an increase in sympathetic activity, which seems to be determinant in the maintenance of hypertension in this experimental model.

Key Words: Hypertension, Hypoxia, Sympathetic activity

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