Reduction of elevated arterial blood pressure in obese Zucker rats by inhibition of ganglionic long-term poteniation

Sustained enhancement of the basal tone of ganglionic transmission is expected to result in an enduring increase in peripheral resistance that would lead to elevated blood pressure. Long-term potentiation of sympathetic ganglia is an activity-dependent long-lasting increase in strength of ganglionic transmission. Therefore, ganglionic long-term potentiation might be involved in the manifestation of neurogenic forms of hypertension. Expression of sympathetic ganglionic long-term potentiation is dependent on activation of 5-HT3 receptor. We examined the possibility that elevated blood pressure in obese Zucker rat, which is reported to be stress-prone, might be partly due to a neurogenic factor resulting from expression of ganglionic long-term potentiation. Chronic treatment with the 5-HT3 receptor antagonist ondansetron (0.5 mg/kg/day) caused a significant decrease in blood pressure of the obese Zucker rats without affecting that of normotensive lean Zucker rats. Electropysiological procedures to test for long-term potentiation in isolated ganglia suggest that ganglionic long-term potentiation has been previously expressed in vivo in ganglia from obese Zucker rat but not in those from the normotensive lean Zucker rats. The results indicate that expression of ganglionic long-term potentiation in sympathetic ganglia may be responsible for neurogenic increase in blood pressure, which contributes to the moderate hypertension often seen in the obese Zucker rats. (C) 2002 Elsevier Science Ltd. All rights reserved.