We have previously described a rat model that responds to repetitive episodic hypoxia (FiO 2 nadir 3-5% for 12 seconds every 30 seconds for 7 hr/day for 35 days) with chronic increase in arterial blood pressure. The purpose of the current study was to determine if peripheral sympathetic nervous system denervation blocks this persistent blood pressure elevation. Chemical sympathetic denervation was achieved and maintained by three intraperitoneal injections (100 mg/kg 6-hydroxydopamine) on days 1, 3, and 27 of a 47-day experiment in two groups of rats. One denervated group was subjected to episodic hypoxia for 40 consecutive days beginning on day 7 and the other remained unhandled in their usual cages. A third group was injected with vehicle only and subjected to the same episodic hypoxia while a fourth group remained unhandled for 40 days. The vehicle-treated, episodic hypoxia-exposed group showed a 7.7 mm Hg increase in mean arterial blood pressure (conscious, unrestrained) over the 40-day period, whereas all other groups showed a decrease in mean arterial pressure. The left ventricle and septum/whole body weight ratio was higher in both episodic hypoxia-exposed groups at the end of the study. Plasma epinephrine in both groups administered 6-hydroxydopamine was higher on day 6 than in the vehicle-injected rats. Measurement of catecholamines in cardiac muscle homogenate confirmed denervation in 6-hydroxydopamine animals. These results indicate that the peripheral sympathetic nervous system is necessary for the persistent increase in blood pressure in response to repetitive episodic hypoxia. emia is associated with acute elevation of blood pressure, and in up to 50% of patients with chronic apnea, persistent elevation of daytime blood pressure is seen. '-3 Repetitive acute hypoxia with heightened sympathetic nerve activity could play an important role in the persistent elevation of blood pressure seen in some patients.With some species variability, acute hypoxemia causes increased heart rate, variable changes in arterial pressure, and increased cardiac contractility and output through stimulation of central and peripheral chemoreceptors and perhaps other local effects.4 -6 The effector arm of this reflex involves increased sympathetic discharge. Plasma norepinephrine is elevated in acute hypoxia, 7 -8 and urinary catecholamine elevation in patients with severe sleep apnea is reversed by tracheostomy.9 Acute hypoxia induces elevated blood pressure and increased microneurographic amplitude, implying increased postganglionic sympathetic activity. 1011 In spontaneously hypertensive rats (SHR) 12 and in humans with borderline hypertension, the sympathetic response to acute hypoxia is exaggerated. 13 The response is further exaggerated in borderline hypertensive humans when apnea is added to acute hypoxia.14 Finally, muscle nerve sympathetic activity recorded during apnea in humans shows a progressive increase throughout the apnea followed by an abrupt reduction at apnea termination.
15A key concept in the above hy...