TY - JOUR
T1 - Abnormal sympathetic overactivity evoked by insulin in the skeletal muscle of patients with essential hypertension
AU - Lembo, Giuseppe
AU - Napoli, Raffaele
AU - Capaldo, Brunella
AU - Rendina, Virgilio
AU - Laccarino, Guido
AU - Volpe, Massimo
AU - Trimarco, Bruno
AU - Saccà, Luigi
PY - 1992
Y1 - 1992
N2 - The reason why hyperinsulinemia is associated with essential hypertension is not known. To test the hypothesis of a pathophysiologic link mediated by the sympathetic nervous system, we measured the changes in forearm norepinephrine release, by using the forearm perfusion technique in conjunction with the infusion of tritiated NE, in patients with essential hypertension and in normal subjects receiving insulin intravenously (1 mU/ kg per min) while maintaining euglycemia. Hyperinsulinemia (50-60 μU/ml in the deep forearm vein) evoked a significant increase in forearm NE release in both groups of subjects. However, the response of hypertensives was threefold greater compared to that of normotensives (2.28±45 ng·liter-1 · min-1 in hypertensives and 0.80·0.27 ng · liter-1 in normals; P <0.01). Forearm glucose uptake rose to 5.1??·.7 mg · liter-1 · min-1 in response to insulin in hypertensives and to 7.9±1.3 mg · liter1 · min-1 in normotensives (P <0.05). To clarify whether insulin action was due to a direct effect on muscle NE metabolism, in another set of experiments insulin was infused locally into the brachial artery to expose only the forearm tissues to the same insulin levels as in the systemic studies. During local hyperinsulinemia, forearm NE release remained virtually unchanged both in hypertensive and in normal subjects. Furthermore, forearm glucose disposal was activated to a similar extent in both groups (5.0±0.6 and 5.2±1.1 mg · liter-1-min-1 in hypertensives and in normals, respectively). These data demonstrate that: (a) insulin evokes an abnormal muscle sympathetic overactivity in essential hypertension which is mediated by mechanisms involving the central nervous system; and (b) insulin resistance associated with hypertension is demonstrable in the skeletal muscle tissue only with systemic insulin administration which produces muscle sympathetic overactivity. The data fit the hypothesis that the sympathetic system mediates the pathophysiologic link between hyperinsulinemia and essential hypertension.
AB - The reason why hyperinsulinemia is associated with essential hypertension is not known. To test the hypothesis of a pathophysiologic link mediated by the sympathetic nervous system, we measured the changes in forearm norepinephrine release, by using the forearm perfusion technique in conjunction with the infusion of tritiated NE, in patients with essential hypertension and in normal subjects receiving insulin intravenously (1 mU/ kg per min) while maintaining euglycemia. Hyperinsulinemia (50-60 μU/ml in the deep forearm vein) evoked a significant increase in forearm NE release in both groups of subjects. However, the response of hypertensives was threefold greater compared to that of normotensives (2.28±45 ng·liter-1 · min-1 in hypertensives and 0.80·0.27 ng · liter-1 in normals; P <0.01). Forearm glucose uptake rose to 5.1??·.7 mg · liter-1 · min-1 in response to insulin in hypertensives and to 7.9±1.3 mg · liter1 · min-1 in normotensives (P <0.05). To clarify whether insulin action was due to a direct effect on muscle NE metabolism, in another set of experiments insulin was infused locally into the brachial artery to expose only the forearm tissues to the same insulin levels as in the systemic studies. During local hyperinsulinemia, forearm NE release remained virtually unchanged both in hypertensive and in normal subjects. Furthermore, forearm glucose disposal was activated to a similar extent in both groups (5.0±0.6 and 5.2±1.1 mg · liter-1-min-1 in hypertensives and in normals, respectively). These data demonstrate that: (a) insulin evokes an abnormal muscle sympathetic overactivity in essential hypertension which is mediated by mechanisms involving the central nervous system; and (b) insulin resistance associated with hypertension is demonstrable in the skeletal muscle tissue only with systemic insulin administration which produces muscle sympathetic overactivity. The data fit the hypothesis that the sympathetic system mediates the pathophysiologic link between hyperinsulinemia and essential hypertension.
KW - Glucose
KW - Hypertension
KW - Insulin resistance
KW - Norepinephrine release
KW - Sympathetic nervous system
UR - http://www.scopus.com/inward/record.url?scp=0026637065&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026637065&partnerID=8YFLogxK
M3 - Article
C2 - 1634611
AN - SCOPUS:0026637065
VL - 90
SP - 27
EP - 29
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 1
ER -