Insulin and hypertension: a causal relationship?

The association between insulin and hypertension has been extensively explored during the past decade and remains an area of intense discussion and debate. Interest in the link between insulin and high blood pressure was fueled by two distinct observations: (i) the lack of effective antihypertensive drugs to reduce the increased risk of coronary artery disease in hypertensive subjects [l-4] and (ii) the realization that essential hypertension per se is frequently associated with insulin resistance (resistance to the glucoregulatory effects of insulin) and hyperinsulinemia [5,6]. These two observations led to the so-called “insulin hypothesis” of hypertension where it was postulated that insulin resistance and/or hyperinsulinemia may be causally related to the development of hypertension [7,8]. This was an attractive proposition which could help explain the apparent inability of conventional antihypertensive drugs (thiazides, beta blockers) to decrease the incidence of coronary ischemic events, since these drugs did not improve but rather worsened insulin action [9111. Subsequent studies revealed that these defects in glucose metabolism are associated with an atherogenic risk profile and may play a role in the development of hypertension, dyslipidemia, atherosclerosis and coronary artery disease [12191. Recent reports clearly indicate that insulin resistance and hyperinsulinemia are present in normotensive offsprings of patients with hypertension as early as the second decade of life and that these changes antedate the rise in blood pressure (BP) [21,22]. The observation that insulin resistance and hyperinsulinemia occur not only in untreated human hypertensives [24,25] but also in several rodent models of hypertension [ 12,26,27] strengthens the contention that these abnormalities are intrinsically linked