SOME METABOLIC ASPECTS OF ESSENTIAL-HYPERTENSION AND ITS TREATMENT

We tested whether patients with essential hypertension (EH) have metabolic evidence of increased adrenergic activity, and if a relationship exists between carbohydrate metabolism and the blood pressure (BP) response to angiotensin-converting enzyme (ACE) inhibition. Study 1 included 59 subjects who underwent resting ambulatory BP, heart rate, and resting energy expenditure (REE) measurement (by indirect calorimetry). REE was directly related to lean body mass (LBM) (r = 0.56, p < 0.0001) and to fasting plasma insulin levels (p < 0.03), after adjusting for LBM and age) but not to BP. The 38 subjects with EH had significantly higher fasting plasma insulin levels (54 +/- 4 vs 42 +/- 4 pM; p < 0.05) than the 21 normotensive subjects. When normalized by the LBM, the hypertensive patients had significantly higher REE values than the normotensive subjects (89 +/- 2 vs 78 +/- 3 J min-1 . kg-1; p < 0.005). No differences in the other measured variables were found between the two groups. Thus, in this group of lean patients with stable EH, relative hyperinsulinemia is associated with a small increase in REE, the significance of which remains to be determined. In study 2, 20 patients with EH received an oral glucose tolerance test and a euglycemic insulin clamp before and after 3 months of treatment with cilazapril. Glucose-induced insulin response, but not insulin sensitivity, was improved by treatment in the whole group. Before therapy, the 12 responders (diastolic BP <95 mm Hg) had similar glucose tolerance and insulin sensitivity to the eight nonresponders. Responders, however, had lower fractional potassium excretion than nonresponders both during fasting (9.6 +/- 1 vs 16.0 +/- 2.4%; p < 0.02) and during the glucose load (9.1 +/- 1.4 vs 13.1 +/- 1.1%; p < 0.04). In the responders, fasting potassium levels at baseline were directly related to the decrease in BP (p < 0.01) and to the improvement of glucose-induced insulin response (p < 0.04) achieved after treatment. Thus, the therapeutic effect of ACE inhibition is in part related to fractional potassium excretion, which, in turn, affects glucose tolerance through the influence of potassium levels on glucose-induced insulin release.