Effect of insulin-induced hypokalemia on lumbar sympathetic nerve activity in anesthetized rats

Acute euglycemic hyperinsulinemia produces sympathoexcitation and a profound fall in plasma potassium levels. Because hypokalemia may activate the renin-angiotensin system to produce the observed increases in sympathetic nerve activity (SNA), the present study was designed to determine whether acute euglycemic-hyperinsulinemia in rats causes decreases in plasma potassium accompanied by increases in plasma renin activity (PRA) as well as elevations in SNA, and whether these alterations would be prevented by maintaining normokalemia with an exogenous potassium infusion.

We infused vehicle (control; n = 10) or insulin (10 mU/min) in anesthetized untreated rats (insulin; n = 11), or in rats receiving simultaneous KCl infusion (Insulin + K+; n = 10), while measuring mean arterial pressure (MAP), heart rate (HR), SNA, plasma potassium, and PRA during euglycemic clamp.

As expected, insulin rats had a large fall in plasma potassium (4.6 +/- 0.1 to 3.9 +/- 0.1 mEq/l), contrasting with no change in the control (4.8 +/- 0.2 to 4.8 +/- 0.2 mEq/l) and insulin + K+ (4.4 +/- 0.1 to 4.6 +/- 0.2 mEq/l) groups. However, PRA levels at study completion were not different in the three experimental groups. In addition, insulin rats had large increases in lumbar SNA (194 +/- 11% from 100% baseline) compared with modest elevations in control rats (122 +/- 10%), and prevention of hypokalemia failed to affect sympathetic increases (213 +/- 20%) in insulin + K+ rats. MAP and HR did not change in any of the experimental groups.

These findings indicate that insulin per se, rather than insulin-induced hypokalemia or hormonal and compensatory adjustments secondary to hypokalemia, is the main mechanism that triggers increases in lumbar SNA.