BACKGROUND: Recently published studies in experimental animals support earlier findings in humans implicating the splanchnic sympathetic nerves in the pathophysiology of hypertension. Most of these new studies show a role for splanchnic sympathetic nerves in the development of hypertension. Experiments reported here were to investigate if splanchnic denervation might be an effective antihypertensive intervention in established hypertension.
METHODS: Surgical sympathetic denervation of the splanchnic organs (with minimal effects on the renal innervation) via celiac ganglionectomy (CGX) was performed in rat and mouse models of established hypertension. Blood pressure and heart rate were monitored chronically and continuously before and after ganglionectomy using radiotelemetry. Efficacy and selectivity of sympathetic denervation was evaluated using HPLC-based measurements of norepinephrine content in splanchnic organs.
RESULTS: CGX consistently led to > 90% depletion of norepinephrine content in liver, spleen and intestine in all animals. Renal norepinephrine content was reduced by 0 - 40%. In normotensive and hypertensive Schlager mice, CGX caused no sustained effects on any hemodynamic variable. In normotensive rats, CGX induced a small but persistent fall in arterial pressure. In hypertensive SHRSP and SHROB rats, CGX produced no sustained change in hemodynamics. However CGX caused small but significant decreases in arterial pressure (~ 10 mmHg) in hypertensive SHR, DOCA-salt and Dahl S rats (on low or high salt intake). Finally, in a genetic model of neurogenic hypertension caused by over-expression of the endothelin B receptor in sympathetic ganglia, CGX completely normalized arterial pressure.
CONCLUSIONS: Splanchnic sympathetic nerves make a widely variable contribution to arterial pressure regulation in experimental models of hypertension. These findings—along with older results in human patients—suggest that targeted splanchnic sympathectomy could have a place in the management of hypertension in selected patients.
DISCLOSURE: I am a consultant to Medtronic and Ardelyx.