Direct Recording of Renal Sympathetic Nerve Activity in Unrestrained, Conscious Mice

Abstract

Renal sympathetic nerve activity (RSNA) has been measured in anesthetized mice. However, anesthesia and acute surgical preparation cause poor cardiovascular stability and unphysiological blood pressures. This compromised physiological state confounds proper interpretation of experimental results considering the inseparable link between cardiovascular status and autonomic nervous tone. We, therefore, developed a surgical and experimental protocol for measuring RSNA in conscious, unrestrained mice. Male C57Bl/6J mice were chronically instrumented with blood pressure radiotelemeters, an indwelling jugular venous catheter and a bipolar electrode for recording RSNA. Mice were placed in a home cage and left to recover for 48 to 72 hours. Survival rate was 100%; all of the mice exhibited normal behavior with no sign of distress 24 hours after surgery. RSNA was successfully recorded in 80% of the mice at 48 and 72 hours postsurgery; viable RSNA was reduced to 70% and 50% at 4 and 5 days postsurgery, respectively. Mean arterial pressure (116±2 mm Hg; n=10) was consistent with values reported previously for conscious mice. RSNA increased with the normal physical activities of eating and grooming and was validated by ganglionic blockade and pharmacological manipulation of blood pressure; reduction in blood pressure to 62±3 mm Hg with nitroprusside increased RSNA by 77±9% above baseline (n=5; P<0.05), whereas an increase in blood pressure to 137±6 mm Hg with phenylephrine reduced RSNA by 79±2% compared with baseline (n=5; P<0.05). Thus, we demonstrate an accessible and effective method for direct assessment of RSNA in conscious, unrestrained mice.