Effect of angiotensin converting enzyme inhibitor (lisinopril) on insulin sensitivity and sodium transport in mild hypertension

The purpose of this study was to determine whether antihypertensive therapy with the angiotensin converting enzyme inhibitor lisinopril would alter cell Na+ transport kinetics, metabolic parameters associated with insulin resistance, or both in young adults with mild hypertension. Sixteen young adults (mean age 29 ± 4 years) were treated with placebo for 8 weeks, then with lisinopril for 12 weeks. Metabolic risk factors examined included plasma lipid levels, plasma insulin concentration during an oral glucose tolerance test, and insulin sensitivity determined by an euglycemic hyperinsulinemic clamp procedure. Red blood cells were assayed for Na+/H+ exchange, Na+/Li+ exchange, Na+-K+ pump activity, and Na+-K+-Cl− cotransport before and during treatment. Blood pressure decreased from 142 ± 4/98 ± 2 mm Hg before treatment to 131 ± 3/85 ± 1 mm Hg during lisinopril treatment (P< .001). During lisinopril treatment, there was a significant reduction in total cholesterol (from 177 ± 8 to 161 ± 8 mg/dL, P< .008), in low density lipoprotein-cholesterol (from 107 ± 7 to 91 ± 7 mg/dL, P< .002), and in insulin at 60 min into the oral glucose tolerance test (from 132 ± 18 to 99 ± 15 μU/mL, P< .05). There was a marginally significant increase in insulin sensitivity during lisinopril treatment (P< .08). The assays of cell Na+ transport showed a significant reduction in maximal activity (Vmax) for Na+/H+ exchange (from 33.7 ± 3.8 to 19.7 ± 2.6 mmol/L cell/h, P< .003). There was also a decrease in the Vmax for Na+-K+-Cl− cotransport (from 0.77 ± 0.12 to 0.46 ± 0.07 mmol/L cell/h, P< .016) and a decrease in the concentration of Na+ for half-maximum activity (from 18.4 ± 2.5 to 12.3 ± 1.4 mmol/L cell, P< .04). Changes in Na+ transport appeared to be related to the fall in blood pressure rather than to changes in the metabolic parameters. The effect of lisinopril on insulin sensitivity appeared to be independent of its effect on red blood cell Na+ transport.