Hypothalamic Paraventricular Nucleus Contributes to the Sympathoexcitatory Effects of Hyperinsulinemia

Abstract

Hyperinsulinemia increases sympathetic nerve activity (SNA) and contributes to cardiovascular dysfunction in obesity and diabetes. PVH neurons regulate SNA through mono and poly‐synaptic connections to preganglionic neurons in the spinal cord. The present study determined whether PVH neurons contribute to the increase in SNA during hyperinsulinemia. Hyperinsulinemic‐euglycemic clamps were performed in anesthetized male Sprague‐Dawley rats (370–420 g) by an infusion of insulin (7.5 mU/kg/min) and 50% dextrose (0.75–2.0 ml/h) for 90 min. Insulin significantly increased lumbar SNA (101 ± 13%, P<0.01) and arterial blood pressure (baseline: 111 ± 2 mmHg vs 60 min: 124 ± 3 mmHg, P<0.01) without any change in renal SNA (8 ± 9%) or plasma glucose levels (baseline: 79 ± 14 vs 60 min: 82 ± 10 mg/dl). Inhibition of the PVH with bilateral injection of the GABAA agonist muscimol (500 pmol/100 nl, n=4) significantly reduced the increase in lumbar SNA (93 ± 20% to 32 ± 19%) and arterial blood pressure (13 ± 4 to 2 ± 3 mmHg). Injection of isotonic saline into the PVH (n=3) did not alter lumbar SNA (131 ± 24% versus 143 ± 2%) or arterial blood pressure (10 ± 3 vs 10 ± 3 mmHg). Similarly, injection of muscimol outside of the PVH (n=3) did not effect the increase in lumbar SNA (113 ± 16% vs 126 ± 27%) or arterial blood pressure (11 ± 3 vs 9 ± 3 mmHg). These findings indicate that PVH neurons contribute to the sympathoexcitatory effects of hyperinsulinemia.