EFFECTS OF INSULIN ON VASCULAR TONE AND SYMPATHETIC NERVOUS-SYSTEM INNIDDM

Chronic activation of the sympathetic nervous system may be a pathogen etic mechanism by which hyperinsulinemia induces cardiovascular damage in insulin-resistant NIDDM patients. The influence of physiological h yperinsulinemia (similar to 700 pmol/l) on basal and stimulated sympat hetic outflow was studied in 12 lean normotensive subjects with well-c ontrolled NIDDM without complications and in 13 matched control subjec ts, Forearm blood flow (FBF) was measured with forearm plethysmography ; sympathetic nervous system activity was assessed by the [H-3]norepin ephrine (NE) tracer method, NIDDM patients were insulin resistant (glu cose infusion rates 31.8 +/- 3.8 vs, 48.7 +/- 2.0 mu mol . kg(-1). min (-1) in control subjects, P < 0.01). After a mixed meal, NIDDM patient s showed a hyperinsulinemic response (2-h insulin levels: NIDDM patien ts 324 +/- 34 pmol/l, control subjects 165 +/- 19 pmol/l, P < 0.001). Insulin infusion induced a vasodilator response (not significantly dif ferent between the groups), Arterial plasma NE levels and total-body N E spillover increased significantly (total spillover in NIDDM patients horn 0.77 +/- 0.09 to 1.18 +/- 0.16 nmol . m(-3). min(-1), in control subjects from 0.98 +/- 0.14 to 1.23 +/- 0.18 nmol . m(-2). min(-1), P < 0.01 for all, not different between groups). Total-body NE clearanc e did not change, Sympathetic stimulation (lower-body negative pressur e [LBNP] 15 mmHg) induced forearm vasoconstriction and increased arter ial and venous plasma NE and total NE spillover, Responses of FBF and NE kinetics to LBNP were not significantly different between groups an d were not altered by hyperinsulinemia. Although these nonobese subjec ts with uncomplicated NIDDM showed postprandial hyperinsulinemia and r esistance to the effect of insulin on glucose metabolism, this group w as not resistant to the vasodilator and sympathetic stimulant effects of insulin, Responses to sympathetic stimuli (LBNP) were normal and un affected by physiological hyperinsulinemia, Therefore, because of dail y life hyperinsulinemia, chronic sympathetic stimulation could be oper ative in these patients and may explain the increased incidence of hyp ertension and/or cardiovascular complications.