The Effects of Lacidipine on Insulin Sensitivity

Abstract

Clinical and pathophysiological associations between obesity, noninsulin-dependent diabetes mellitus (NIDDM), and essential hypertension have raised important questions about the role of insulin resistance in both the etiology and clinical course of hypertension. Loss of tissue sensitivity to the actions of insulin, i.e., insulin resistance, leads to a rise in circulating insulin levels and, when this compensatory hyperinsulinemic response is insufficient, to impaired glucose tolerance or type II diabetes. Insulin resistance is a well-recognized feature of obesity and NiDDM, but more recently evidence has shown that lean nondiabetic essential hypertensives are also insulin resistant and hyperinsulinemic compared with well-matched normotensive controls (1). Moreover, treated hypertensives may remain insulin resistant which may contribute to the apparent deficiencies of antihypertensive treatment in reducing coronary heart disease mortality. Dyslipidemia is an accompanying metabolic feature of insulin resistance and generally there is a positive correlation between plasma insulin and triglyceride concentrations and an inverse relationship between insulin and high-density lipoprotein cholesterol (2). In addition to these adverse lipid effects, hyperinsulinemia itself may be an independent risk factor for coronary heart disease (3) and this epidemiological evidence is supported by numerous experimental studies showing that insulin accelerates atherosclerosis (4). Interestingly, insulin resistance and hyperinsulinemia also occur in classic rodent models of hypertension, for example, the spontaneously hypertensive rat (SHR) and the Dahl salt-sensitive animal (5). In addition, Reaven showed some time ago that replacing the usual carbohydrate in rat chow with fructose led to a state of insulin resistance, hyperinsulinemia and hypertension within 21 days (6). Moreover, exercise training and somatostatin administration (interventions which enhance insulin sensitivity and lower plasma insulin concentrations) attenuate the rise in blood pressure associated with this dietary intervention (7).