Salt sensitivity is associated with insulin resistance, sympathetic overactivity, and decreased suppression of circulating renin activity in lean patients with essential hypertension123

Background: The mechanisms by which a derangement of glucose metabolism causes high blood pressure are not fully understood. Objectives: This study aimed to clarify the relation between salt sensitivity of blood pressure and insulin resistance, which are important subcharacteristics of hypertension and impaired glucose metabolism, respectively. Effects on the renin-angiotensin and sympathetic nervous systems were also studied. Design: The state of glucose metabolism was assessed by a hyperinsulinemic euglycemic glucose clamp technique and a 75-g oral-glucose-tolerance test in 24 essential hypertensive patients who were lean and without diabetes or chronic kidney disease. The subjects were classified as salt-sensitive or salt-resistant on the basis of the difference (Δ mean blood pressure ≥5%) between 24-h ambulatory blood pressure monitoring results on the seventh day of low-salt (34 mmol/d) and high-salt (252 mmol/d) diets. Urine and blood samples were collected for analyses. Results: There was a robust inverse relation between the glucose infusion rate (GIR) and the salt sensitivity index. The GIR correlated directly with the change in urinary sodium excretion and was inversely related to the change in hematocrit when the salt diet was changed from low to high, which is indicative of salt and fluid retention in salt-sensitive subjects. The GIR also showed an inverse correlation compared with the changes in urinary norepinephrine excretion, plasma renin activity, and plasma aldosterone concentration. Conclusions: Salt sensitivity of blood pressure is strongly associated with insulin resistance in lean, essential hypertensive patients. Hyperinsulinemia, sympathetic overactivation, and reduced suppression of the renin-angiotensin system may play a role in this relation.