Does PVN Neuropeptide Y contribute to the sympathoexcitatory effect of insulin in the arcuate nucleus?

Abstract

Insulin acts in the Arcuate Nucleus (ArcN) to increase lumbar sympathetic nerve activity (LSNA) and LSNA baroreflex gain (BRG) via a pathway that includes the hypothalamic paraventricular nucleus (PVN). Two ArcN neuronal types project to PVN: melanocortin (MC) and Neuropeptide Y (NPY). Recent data implicates MC in the sympathoexcitatory effect of insulin, but whether NPY also contributes is unknown. To test this hypothesis, we determined if inhibition of PVN NPY type 1 receptors (Y1x) reduces the effect of ArcN insulin to increase LSNA and LSNA BRG. In chloralose‐anesthetized female rats, bilateral microinjection (60nL) of insulin in ArcN (n=3; 0.06nU) increased (P<0.05) LSNA (132±7%) and LSNA BRG (3.9±0.4 to 6.9±0.6 %/mmHg). PVN Y1x (n=5; BIBO3304; 60pmol) also increased (P<0.05) LSNA (161±14%) and LSNA BRG (3.5±0.5 to 5.4±0.9 %/mmHg), indicating endogenous NPY inhibits LSNA. ArcN insulin and PVN Y1x given together (n=5) did not increase LSNA (155±12%; P<0.05) or LSNA BRG (3.4±0.5 to 6.0±1.2 %/mmHg; P<0.05) more than either alone, suggesting a converging pathway. Conversely, microinjection of NPY in PVN (n=3; 6pmol) decreased (P<0.05) LSNA (68±14%) and LSNA BRG (5.8±0.6 to 3.4±0.4 %/mmHg), and PVN NPY and ArcN insulin together (n=3) produced similar decreases in LSNA (63±15%; P<0.05) and LSNA BRG (4.9±1.3 to 2.9±0.9 %/mmHg; P<0.05). Thus, PVN NPY blocked the effect of ArcN insulin. These data support the hypothesis that ArcN insulin increases LSNA and LSNA BRG in part via inhibition of PVN‐projecting NPY neurons. Support: HL088552.