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This study examined the relationship between cerebral blood flow (CBF) and end-tidal PCO2 (PETCO2) in humans. We used transcranial Doppler ultrasound to determine middle cerebral artery peak blood velocity responses to 14 levels of PETCO2 in a range of 22 to 50 Torr with a constant end-tidal PO2 (100 Torr) in eight subjects. PETCO2 and end-tidal PO2 were controlled by using the technique of dynamic end-tidal forcing combined with controlled hyperventilation. Two protocols were conducted in which PETCO2 was changed by 2 Torr every 2 min from hypocapnia to hypercapnia (protocol I) and vice-versa (protocol D). Over the range of PETCO2 studied, the sensitivity of peak blood velocity to changes in PETCO2 (CBF-PETCO2 sensitivity) was nonlinear with a greater sensitivity in hypercapnia (4.7 and 4.0%/Torr, protocols I and D, respectively) compared with hypocapnia (2.5 and 2.2%/Torr). Furthermore, there was evidence of hysteresis in the CBF-PETCO2 sensitivity; for a given PETCO2, there was greater sensitivity during protocol I compared with protocol D. In conclusion, CBF-PETCO2 sensitivity varies depending on the level of PETCO2 and the protocol that is used. The mechanisms underlying these responses require further investigation.

Abstract-Intermittent hypoxia (IH) is believed to contribute to the pathogenesis of hypertension in obstructive sleep apnea through mechanisms that include activation of the renin-angiotensin system. The objective of this study was to assess the role of the type I angiotensin II receptor in mediating an increase in arterial pressure associated with a single 6-hour IH exposure. Using a double-blind, placebo-controlled, randomized, crossover study design, we exposed 9 healthy male subjects to sham IH, IH with placebo medication, and IH with the type I angiotensin II receptor antagonist losartan. We measured blood pressure, cerebral blood flow, and ventilation at baseline and after exposure to 6 hours of IH. An acute isocapnic hypoxia experimental protocol was conducted immediately before and after exposure to IH. IH with placebo increased resting mean arterial pressure by 7.9Ϯ1.6 mm Hg, but mean arterial pressure did not increase with sham IH (1.9Ϯ1.5 mm Hg) or with losartan IH (Ϫ0.2Ϯ2.4 mm Hg; PϽ0.05). Exposure to IH prevented the diurnal decrease in the cerebral blood flow response to hypoxia, independently of the renin-angiotensin system. Finally, in contrast to other models of IH, the acute hypoxic ventilatory response did not change throughout the protocol. IH increases arterial blood pressure through activation of the type I angiotensin II receptor, without a demonstrable impact on the cerebrovascular or ventilatory response to acute hypoxia. (Hypertension. 2010;56:369-377.)Key Words: blood pressure Ⅲ cerebrovascular circulation Ⅲ hypoxia Ⅲ renin Ⅲ physiology P atients with obstructive sleep apnea (OSA) are exposed to chronic intermittent hypoxia (IH), which is thought to be the underlying mechanism that links OSA with an increased risk of cardiovascular disease. 1 The specific pathophysiologic mechanism whereby OSA causes hypertension has not been fully elucidated, but it has been proposed that persistent sympathoexcitation, oxidative stress, and endothelial dysfunction contribute. 2 Central to this concept is the important interaction between the sympathetic nervous system and the renin-angiotensin system (RAS). Renin release from the kidney is tightly controlled by activity in renal sympathetic nerves. 3 In OSA patients, sympathetic nerve activity, 4 the plasma concentration of angiotensin II (ANG-II), 5 and the vasoconstrictor response to ANG-II are elevated. 6 ANG-II has potent vasoconstrictor capabilities through its action on type I ANG-II receptors (AT 1 Rs) located on vascular smooth muscle cells. 7 ANG-II production can also regulate blood volume by increasing aldosterone production. The combined potential for the RAS to be stimulated by IH and its ability to regulate peripheral resistance and blood volume make it a credible pathway through which OSA can lead to the development of systemic hypertension. The role of the RAS in the IH-dependent increase in arterial blood pressure has yet to be addressed in human experiments.The primary objective of this study was to assess the role of the AT 1 R in ...