Inhibition of nitric oxide synthesis attenuates insulin-mediated sympathetic activation in rats.
OBJECTIVE
Infusion of insulin produces sympathoexcitation, nitric oxide (NO) generation and NO-mediated vasodilation. Because central nervous system NO may inhibit sympathetic outflow, the present study was designed to determine whether NO synthase blockade would enhance insulin-mediated sympathetic activation. We additionally aimed to determine whether augmented sympathoexcitation and reduced NO-mediated vasodilation, during combined NO synthase blockade and hyperinsulinemia, would result in a blood pressure increase.


METHODS
We infused vehicle (Control; n = 7) or insulin (10 mU/min) in anaesthetized rats receiving either no pretreatment (Insulin; n = 7) or after pretreatment with the NO blocker, NG-monomethyl-L-arginine (L-NMMA-insulin; 0.25 mg/kg per min; n = 7), while measuring mean arterial pressure (MAP), heart rate and lumbar sympathetic nerve activity (SNA) during euglycemic clamp. An additional control group received L-NMMA (L-NMMA; n = 7).


RESULTS
Insulin rats had large SNA increases (190 +/- 22% from 100% baseline), contrasting with small increases in the Control (136 +/- 10%) and L-NMMA (135 +/- 20%) groups. Unexpectedly, NO blockade abolished insulin-induced SNA increases in the L-NMMA-insulin group (96 +/- 12%). In agreement with the SNA findings, Insulin rats had heart rate increases while no heart rate changes were observed in the L-NMMA-insulin, Control, or L-NMMA groups. In addition, there was an unexpected was a lack of MAP increase in L-NMMA-insulin rats. MAP also did not change in the Control, L-NMMA or Insulin groups.


CONCLUSIONS
These findings suggest that NO is necessary for insulin to exert its sympathoexcitatory effects, and that insulin-induced NO release may play a role in activating increases in lumbar SNA.
Muntzel
M S
MS
Department of Biological Sciences, Lehman College, Bronx, New York 10468, USA. martinmu@alpha.lehman.cuny.edu
Malena
H
H
Drüeke
T
T
D000818:Animals; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D008161:Lumbosacral Region; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004338:Drug Combinations; D004791:Enzyme Inhibitors; D007328:Insulin; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase