Insulin resistance, hyperinsulinemia, and hypertriglyceridemia in the etiology and clinical course of hypertension. Patients with untreated hypertension have been shown to be resistant to insulin-stimulated glucose uptake and are more hyperinsulinemic and hypertriglyceridemic than matched groups of patients with normal blood pressure. In addition, insulin resistance, hyperinsulinemia, and hypertriglyceridemia have been demonstrated in spontaneous hypertensive rats and in Sprague-Dawley rats fed a fructose-enriched diet. The defect in insulin-stimulated glucose uptake in these experimental models can also be shown at the cellular level. Experimental interventions that prevent insulin resistance or hyperinsulinemia from developing in fructose-fed rats also greatly attenuate the increase in blood pressure. Since endogenous hyperinsulinemia and hypertriglyceridemia have been identified as factors that increase the risk of coronary artery disease (CAD), it is likely that they contribute to the increased prevalence of CAD in hypertensive patients. Antihypertensive treatment may have exacerbated these metabolic abnormalities, which could help explain why it has been difficult to show that lowering blood pressure decreases the risk of CAD. These observations raise the possibility that abnormalities of carbohydrate and lipoprotein metabolism may play a role in both the etiology and clinical course of hypertension. 