A Novel Method for Measurement of Cardiovascular Responses to Lower Body Negative Pressure in the Awake Instrumented Rat.

Lower body negative pressure (LBNP) has been used for decades in humans to model arterial baroreceptor unloading and represents a powerful tool for evaluating cardiovascular responses to orthostatic challenge. However, LBNP studies in animals have been limited to conditions of anesthesia or sedation, where cardiovascular reflexes are altered. Given the consequent uncertainties, the usefulness of LBNP studies in these preclinical models has been severely hampered. Here we developed an approach using a novel system to study LBNP responses in awake rats instrumented for telemetric blood pressure (BP) measurement. BP responses to progressive levels of LBNP (-3 to -15 mmHg) were first made in awake rats, followed by measurements under various treatments. In awake untreated rats, BP was well maintained up to -15 mmHg LBNP, and there was a robust baroreceptor response in heart rate (HR). Under anesthesia with 3% isoflurane, BP was not maintained at LBNP below -3 mmHg, and baroreceptor responses in HR were completely blocked, confirming the limited usefulness of this method under anesthesia. Interrogation of the autonomic pathways involved in the response revealed that muscarinic (atropine) and β-adrenergic (atenolol) blockade, separately or together, blocked the HR responses, but BP remained well maintained. α-adrenergic blockade (prazosin) severely blunted the ability to maintain BP in response to LBNP. These data are consistent with findings in human subjects in that the vascular component of the orthostatic reflex predominates in preserving BP. Validation of this novel method provides a valuable tool for investigating orthostatic (in)tolerance in a facile preclinical model.