Differences in response to the peptidyldipeptide hydrolase inhibitors SQ 20,881 and SQ 14,225 in normal-renin essential hypertension.
We compared vascular and hormonal responses to teprotide (SQ 20,881) and captopril (SQ 14,225) in patients with normal renin essential hypertension given a 10 mEq sodium diet. In 10 patients receiving SQ 20,881, significant changes occurred in diastolic blood pressure (DBP, -13 +/- 2.5 mm Hg), angiotensin II (-7.1 +/- 2.1 pg/ml), and plasma renin activity (PRA, +6.6 +/- 1.9 ng/ml/hr) (p < 0.01 in all cases). Twenty-one patients receiving SQ 14,225 had significant changes in mean DBP (-18 +/- 1.5 mm Hg), angiotensin II (-6.6 +/- 1.5 pg/ml), and PRA (+7.8 +/- 2.4 ng/ml/hr) (all p values < 0.01). In spite of a significantly greater hypotensive response (p < 0.02), patients receiving SQ 14,225 showed increments in PRA and decrements in angiotensin II that did not differ significantly from those seen after SQ 20,881. Moreover, there was a significant change in plasma kinins in patients receiving SQ 20,881 (+2.0 +/- 0.9 ng/ml, p < 0.01) but no change in kinins in patients receiving SQ 14,225 (0.0 +/- 0.1, ns). We conclude that there are important differences in the mechanism mediating the hypotensive response to SQ 20,881 and SQ 14,225 in normal renin essential hypertension.