Neurohumoral, hemodynamic and microvascular changes as mechanisms of insulin resistance in hypertension: a provocative but partial picture.

Hyperinsulinemia and insulin resistance are largely explained by upper body obesity in hypertension. However, non-obese hypertensive patients have similar metabolic defects. Thus, neurohumoral, hemodynamic, and microvascular abnormalities which occur in the development of hypertension may contribute to insulin resistance independent of obesity. Sympathetic drive and vascular alpha-tone are increased in young, predominantly overweight patients with borderline-mild hypertension. The importance of increased neurogenic tone, especially the alpha-adrenergic component, is emphasized by evidence that alpha 1-receptor antagonists virtually normalize insulin metabolism in hypertensive patients. Patients with mild hypertension have elevated forearm vascular resistance which could theoretically contribute to insulin resistance by impairing muscle perfusion. However, blood flow is normal at baseline and maximal dilation. Similarly, overweight young men have hyperinsulinemia, despite higher basal forearm blood flow and a normal vasodilator reserve. Thus, insulin resistance is not uniformly determined by basal blood flow or flow reserve. However, defects in regional flow distribution or in dynamic flow responses may alter insulin action. Microvascular rarefaction may contribute to insulin resistance in hypertensive patients by increasing diffusion distance for insulin to sites of action. The independent role of capillary density is unknown, since it correlates with muscle fiber type. Furthermore, in the absence of significant kinetic differences for insulin's multiple actions in skeletal muscle, structural vascular abnormalities would likely cause global defects rather than specific abnormalities in non-oxidative glucose disposal. Theories linking neurohumoral, hemodynamic and microvascular abnormalities in hypertension to insulin resistance are intriguing but unproven. Since insulin resistance has important implications in human disease, further research on mechanisms of this resistance is important.