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.
D000328:Adult; D000804:Angiotensin II / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007705:Kinins / Q000097:blood; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use*; D011392:Proline / Q000031:analogs & derivatives*; D012083:Renin / Q000097:blood*; D013722:Teprotide / Q000627:therapeutic use*; D013997:Time Factors
D007705:Kinins; D009842:Oligopeptides; D000804:Angiotensin II; D011392:Proline; D002216:Captopril; D013722:Teprotide; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D012083:Renin