Chronic Mild Stress Increases Baseline Renal Sympathetic Nerve Activity and the Response to Acute Stressors in Conscious Rats

Abstract

Depression is a non‐traditional risk factor for cardiovascular morbidity and mortality. Increased sympathetic tone is also recognized as deleterious to cardiovascular health. Chronic mild unpredictable stress paradigm (CMS) is a validated model of depression that has been associated with cardiovascular dysfunction in rats. We hypothesized that rats exposed to CMS will have higher arterial pressure and renal sympathetic nerve activity (RSNA) and enhanced responses to acute stressors. Male Sprague Dawley rats were equipped with telemetry transmitters for hemodynamic monitoring and subjected to 4 weeks of CMS or standard housing (control). During the last week, rats were equipped with telemetry transmitters for renal nerve recording. Baseline RSNA was obtained a minimum of 3 days after completion of CMS protocol and the rats were subjected to air jet stress and nasopharygeal reflex testing. Baseline arterial pressure was higher in CMS rats. Baseline RSNA was 0.80 ± 0.05 mV.s in control vs 1.20 ± 0.14 mV.sec in CMS rats (P < 0.05). Peak responses to either air jet stress or nasopharyngeal stimulation were significantly higher in the CMS rats. Although the latencies of the responses were shorter and the duration of the responses were longer in the CMS group, these did not achieve significance. The area under the curve (AUC = latency × duration) for air jet stress was 82% greater for air jet stress and 362% greater for nasopharygeal stimulation in the CMS vs control rats (P < 0.05 for both vs control). These results support the concept that rats subjected to a chronic unpredictable stress paradigm that models depression display higher basal sympathetic nerve activity and a more robust response to acute stress. This enhanced sympathetic tone and neuroexcitability may contribute to increased cardiovascular risk.Support or Funding InformationVA Merit Grant to NFR