Ventilatory responses to chemoreflex stimulation are not enhanced by angiotensin II in healthy humans.

The chemoreflexes exert significant control over respiration and sympathetic outflow. Abnormalities in chemoreflex function may contribute to various disease processes. Based on prior animal studies, we developed the hypothesis that acutely elevating circulating angiotensin II levels into the pathophysiological range increases chemoreflex responsiveness in healthy humans. Eighteen adults were studied before (Pre) and during (Post) low (protocol 1; 2ng/kg/min; n=9) or high (protocol 2; 5ng/kg/min; n=9) dose angiotensin II infusion (study day 1). Chemoreflex responses were quantified by the pure nitrogen breathing method [slope of the minute ventilation vs. arterial oxygen saturation plot generated during a series (n=10) of 100% inspired nitrogen exposures (1-8 breaths)] and by measuring responses to hypercapnia (7% inspired carbon dioxide). Responses to a non-chemoreflex stimulus were also determined (cold pressor test). Measurements were repeated on a subsequent day (study day 2) before and during infusion of a control vasoconstrictor (phenylephrine) infused at a dose (0.6-1.2μg/kg/min) sufficient to increase blood pressure to the same degree as that achieved during angiotensin II infusion. We found that despite increasing plasma angiotensin II levels to pathophysiological levels responses to pure nitrogen breathing, hypercapnia, and the cold pressor test were unchanged by low (2ng/kg/min) and high dose (5ng/kg/min) angiotensin II infusion (protocols 1 and 2). Similarly, responses measured during phenylephrine infusion (Post) were unchanged (from Pre). These findings indicate that acutely increasing plasma angiotensin II levels to levels observed in disease states, such as human heart failure, do not increase chemoreflex responsiveness in healthy humans.