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 th erapy with the angiotensin converting enzyme inhibitor lisinopril woul d alter cell Na+ transport kinetics, metabolic parameters associated w ith insulin resistance, or both in young adults with mild hypertension . Sixteen young adults (mean age 29 +/- 4 years) were treated with pla cebo for 8 weeks, then with lisinopril for 12 weeks. Metabolic risk fa ctors examined included plasma lipid levels, plasma insulin concentrat ion during an oral glucose tolerance test, and insulin sensitivity det ermined by an euglycemic hyperinsulinemic clamp procedure. Red blood c ells were assayed for Na+/H+ exchange, Na+/Li+ exchange, Na+-K+ pump a ctivity, 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). Durin g lisinopril treatment, there was a significant reduction in total cho lesterol (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 1 32 +/- 18 to 99 +/- 15 mu U/mL, P < .05). There was a marginally signi ficant increase in insulin sensitivity during lisinopril treatment (P < .08). The assays of cell Na+ transport showed a significant reductio n in maximal activity (V-max) for Na+/H+ exchange (from 33.7 +/- 3.8 t o 19.7 +/- 2.6 mmol/L cell/h, P < .003). There was also a decrease in the V-max 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 parame ters. The effect of lisinopril on insulin sensitivity appeared to be i ndependent of its effect on red blood cell Na+ transport.