Can Endothelial Dysfunction Cause Hypertension Insulin Resistance And Type Diabetes

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The association between essential hypertension and insulin resistance is well established but presently unexplained. Compensatory hyperinsulinemia has been proposed to be the missing causal link explaining this association. However, this explanation has remained controversial, mostly because acute administration of insulin, despite its presumed prohypertensive effects on the sympathetic nervous system, transmembrane cation transport, and renal sodium reabsorption, leads to vasodilatation (38,39) rather than vasoconstriction, and even exerts a small blood pressure-lowering effect in patients with essential hypertension (40). As an alternative, a connection between the two abnormalities can be envisioned at the level of the microcirculation (Fig. 2).

Recent research suggests that physical integrity and normal function of the arteriolar and capillary network are prerequisites for normal insulin action (38). In addition, disturbances of the microcirculation may initiate the pathogenic sequence in primary

Fig. 2. Microvascular dysfunction as a potential link between common risk factors on the one hand and insulin resistance, type 2 diabetes, hypertension, and renal disease on the other.

hypertension (41) and thus explain, at least in part, the association between insulin resistance and hypertension. An important consequence of this concept is that any condition that impairs microvascular function (42-48) will predispose to both insulin resistance and hypertension (Fig. 2). Thus, if ED in large arteries, an early and prominent event in atherothrombosis, is paralleled by ED in resistance vessels and metabolically important capillary beds that contributes to the development of hypertension and insulin resistance (and later type 2 diabetes), then the association of insulin resistance, diabetes, hypertension, and atherosclerosis may in part have its roots in generalized ED of large and small vessels (49).

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