Microvascular function: a potential link between salt sensitivity, insulin resistance and hypertension

Abstract

Generalized microvascular dysfunction may contribute to the development of salt sensitivity, insulin resistance and hypertension, and may thus link these cardiovascular risk factors. To test this hypothesis, we examined skin microvascular function, salt sensitivity, insulin sensitivity and blood pressure in 27 normotensive and 26 hypertensive individuals. Capillary density was examined by videomicroscopy during venous congestion and postocclusive reactive hyperaemia. Endothelium-(in)dependent vasodilation was assessed by iontophoresis of acetylcholine and sodium nitroprusside and by laser Doppler flowmetry. Salt sensitivity was determined as the difference in mean arterial pressure (MAP) between a 1-week high-salt diet (approximately 235 mmol NaCl/day) versus low-salt diet (approximately 55 mmol NaCl/day). Insulin sensitivity was measured with the hyperinsulinaemic, euglycaemic clamp, and blood pressure was assessed by 24-h ambulatory blood pressure monitoring. Salt sensitivity of blood pressure was inversely associated with postocclusive capillary recruitment and endothelium-dependent vasodilation (r=-0.67, P<0.001 and r=-0.60, P<0.01, respectively), but not with capillary density during venous congestion or endothelium-independent vasodilation. Salt sensitivity was negatively associated with insulin sensitivity (r=-0.55, P<0.001) and positively with MAP (r=0.58, P<0.001). Multiple regression analyses suggested that associations between salt sensitivity and both insulin sensitivity and MAP were dependent on microvascular function. Our results suggest a close inverse association between skin microvascular function and salt sensitivity and a role for generalized microvascular defects as a link between salt sensitivity, insulin resistance and hypertension.