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.

Abstract

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)

• Authors: M McIntyre, R J MacFadyen, P A Meredith, J Menard, H R Brunner, J Insuasty, J L Reid
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 25 Issue 6 Pg. 994-1000 (Jun 1995) ISSN: 0160-2446 [Print] United States
• PMID: 7564347 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Electrolytes
• Pyrimidines
• Tetrazoles
• Angiotensin II
• UP 269-6
• Aldosterone
• Enalapril
• Creatinine
• Renin

Topics

• Administration, Oral
• Adult
• Aldosterone (blood, urine)
• Angiotensin II (blood)
• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors (administration & dosage, adverse effects, pharmacology)
• Blood Pressure (drug effects)
• Creatinine (blood, urine)
• Diet, Sodium-Restricted
• Dose-Response Relationship, Drug
• Double-Blind Method
• Electrolytes (blood, urine)
• Enalapril (administration & dosage, adverse effects, pharmacology)
• Heart Rate (drug effects)
• Humans
• Male
• Pyrimidines (administration & dosage, adverse effects, blood, pharmacology)
• Radioimmunoassay
• Renin (blood)
• Tetrazoles (administration & dosage, adverse effects, blood, pharmacology)