Comparison of the oral angiotensin II receptor antagonist UP 269-6 or enalapril 20 mg on blood pressure and neurohormonal effects in salt-deplete man.
We compared the response of the oral angiotensin II (Ang II) receptor antagonist (ARA) UP 269-6 with an angiotensin converting enzyme inhibitor (ACEI) enalapril 20 mg or placebo, during salt depletion in normal men. We also evaluated safety and tolerability. Sixteen healthy, normotensive male volunteers followed a standardised salt-depletion regimen for 3 days before each study day. Seven different doses of UP 269-6 (5, 10, 20, 40, 80, 120 and 180 mg) were administered double blind in a four-panel dose escalation, with enalapril and placebo randomised within each panel. Supine and erect blood pressure (BP) and heart rate (HR); serum and urinary electrolytes; plasma active renin (PAR), aldosterone, and Ang II were measured at intervals. Urinary electrolytes and aldosterone were measured for the 24 h before dosing and for 24 h after dosing. Dizziness and light-headedness on standing were reported after UP 269-6 at higher doses. Enalapril caused one episode of symptomatic postural hypotension. No other drug-related adverse events (AE) were noted. There was a dose-related decrease in supine and erect systolic and diastolic BP (SBP, DBP) with UP 269-6 at > or = 40 mg, with no change in HR. Based on the maximal decrease in mean arterial pressure (MAP), UP 269-6 at 180 mg had an effect largely comparable to that of enalapril 20 mg. There was a dose-related increase in PAR with UP 269-6. Although this was greater with UP 269-6 180 mg than with enalapril, serum and 24-h urinary aldosterone suppression was greater with enalapril than with any dose of UP 269-6.(ABSTRACT TRUNCATED AT 250 WORDS)
McIntyre
M
M
University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland.
MacFadyen
R J
RJ
Meredith
P A
PA
Menard
J
J
Brunner
H R
HR
Insuasty
J
J
Reid
J L
JL
D000284:Administration, Oral; D000328:Adult; D000450:Aldosterone / Q000097:blood / Q000652:urine; D000804:Angiotensin II / Q000097:blood; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003404:Creatinine / Q000097:blood / Q000652:urine; D004039:Diet, Sodium-Restricted; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004573:Electrolytes / Q000097:blood / Q000652:urine; D004656:Enalapril / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D011863:Radioimmunoassay; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D004573:Electrolytes; D011743:Pyrimidines; D013777:Tetrazoles; D000804:Angiotensin II; C088791:UP 269-6; D000450:Aldosterone; D004656:Enalapril; D003404:Creatinine; D012083:Renin