Assessment of Guanethidine‐induced Neuronal Loss on Basal and Reflex Sympathetic Support of Blood Pressure and Heart rate in the Anesthetized Rat

Abstract

The goal of this study was to determine the degree of sympathetic postganglionic neuronal loss required to impair cardiovascular related sympathetic activity. Rats were treated daily with vehicle (saline, n=10) or guanethidine (100 mg/kg). To produce variable degrees of neuronal loss two separate groups were treated, one for 5 days (n=9) and another for 11 days (n=10), followed by recovery to allow acute effects of guanethidine to dissipate. Sympathetic reflex activity was measured by renal sympathetic nerve activity (RSNA) during baroreflex and chemoreflex testing. Prior to testing, basal RSNA, blood pressure (BP), and heart rate (HR) were recorded. Thoracic ganglia (T13) were examined to determine the extent of postganglionic neuronal loss. Despite some neuronal loss in both treated groups there was no significant effect on resting BP or HR in either group. Rats treated for 5 days had a modest decrease in basal RSNA (63 ± 13%) whereas rats treated for 11 days had significantly lower basal RSNA (37 ± 8%, P < 0.05) compared with vehicle‐treated rats (100 ± 5%). Baroreflex testing in vehicle‐treated rats elicited a 183 ± 20% increase in RSNA. Compared with vehicle‐treated rats baroreflex mediated increases in RSNA were significantly attenuated in 11‐day (59 ± 11%, P < 0.05) but not 5‐day treated rats (122 ± 23%). Chemoreflex testing in vehicle‐treated rats elicited a 270 ± 23% increase in RSNA. Compared with vehicle‐treated rats chemoreflex‐mediated increases in RSNA were significantly attenuated in both the 5‐day (158 ± 32%, P < 0.05) and the 11‐day treated rats (76 ± 15%, P < 0.05). These data provide important insight on the degree of neuronal loss required to impair sympathetic responsiveness and support of BP and HR.