Effect of Lower Body Negative Pressure (LBNP) on Blood Pressure in Awake Rats and Effects of Anesthesia

Abstract

Lower body negative pressure (LBNP) has been used for decades in a variety of settings and species to model orthostatic challenge (OC) and baroreceptor unloading. However, due to physical constraints, measurements of blood pressure (BP) during LBNP have always been made in anesthetized animals, where cardiovascular reflexes are blunted or even blocked. In terminal procedures, for example, urethane is often used in an attempt to preserve some measure of autonomic reflex function during OC. More recently, investigators have used isoflurane in animals fitted with BP telemeters in order to perform longitudinal studies, but the extent to which various cardiovascular reflexes may be preserved is unknown. Here we have developed a novel method to apply lower body negative pressure in awake rats instrumented for BP measurement. Rats were placed into a tubular restraining device (5 cm diameter X 21 cm length), that is divided into an upper and lower chamber by two adjacent latex septa with small holes (~ 2 cm). Rats were positioned so that the septa form a seal at the lower margin of the thorax, thereby creating independent upper and lower chambers. Negative pressure was then applied to the lower chamber using a high-volume vacuum and the pressure controlled using an adjustable damper. BP measurements in response to progressive levels of LBNP (-3 to -15 mmHg) were first made in awake rats, followed by induction of anesthesia and repetition of the LBNP protocol. The effects of pentobarbital (50mg/kg), ketamine/xylazine (70/6 mg/kg) and isoflurane (3%) were determined on separate days. BP and heart rate (HR) responses are shown in the Table. We found that BP was remarkably preserved in awake rats up to at least -9 mmHg LBNP, and thereafter (at -12 and -15 mmHg) decreased modestly. There was a robust baroreceptor-mediated increase in HR beginning at -6 mmHg. By contrast, under each anesthetic, blood pressure decreased dramatically and progressively with increasing LBNP, and the reflex increases in HR were entirely blocked (and actually inverted). These data indicate that the awake rat has robust mechanisms to preserve cardiovascular function during OC, and that these mechanisms are severely compromised during anesthesia. University of Cincinnati College of Medicine Innovation Seed Grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.