Amlodipine and haemodynamic effects of cyclo-oxygenase inhibition.
1. The haemodynamic effects of calcium antagonists could depend at least in part on the activity of vasoactive prostanoids. 2. We set out to study the effect of the cyclo-oxygenase inhibitor ibuprofen, 400 mg three times daily for 3 days, by a randomised cross-over study vs placebo in 12 mild to moderate essential hypertensive patients who had been treated for 1 month with amlodipine. 3. Blood pressure, heart rate and vascular resistances in the upper limb (Doppler ultrasound) were measured. Plasma renin activity and urinary aldosterone, as well as indices of renal function, were evaluated. Urinary 2,3-dinor-6-keto-PGF1 alpha and 2,3-dinor-TXB2, as well as 6-keto-PGF1 alpha and TXB2, were measured as indices of systemic and renal PGI2 and TXA2 synthesis. 4. Amlodipine normalised blood pressure and reduced upper limb vascular resistances; it did not affect urinary prostanoid excretion. Short-term combined administration of ibuprofen resulted in, by comparison with placebo, inhibition of systemic PGI2 (-80.5 ng 24 h-1, 95% CI -99.2, -61.4; P < 0.001) and TXA2 (-216.1 ng 24 h-1, 95% CI -276.5, -155.8; P < 0.001), together with an increase in systolic (+7.8 mm Hg, 95% CI +3.1, +12.3; P < 0.01) and diastolic (+3.9 mm Hg, 95% CI +1.2, +6.6; P < 0.01) blood pressure; it had no significant effect on regional vascular resistances (+4.7 mm Hg ml-1 s, 95% CI -5.6, +15.0). Effects of ibuprofen on renal prostanoid synthesis were less marked, and there was no change in indices of renal function or hydro-electrolytic balance.(ABSTRACT TRUNCATED AT 250 WORDS)
Minuz
P
P
Istituto di Clinica Medica, Università di Verona, Italy.
Pancera
P
P
Ribul
M
M
Priante
F
F
Degan
M
M
Campedelli
A
A
Arosio
E
E
Lechi
A
A
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000328:Adult; D000450:Aldosterone / Q000652:urine; D017311:Amlodipine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood / Q000652:urine; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D007052:Ibuprofen / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D012083:Renin / Q000097:blood; D016037:Single-Blind Method; D013928:Thromboxane A2 / Q000096:biosynthesis; D014463:Ultrasonography; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
D015415:Biomarkers; D016861:Cyclooxygenase Inhibitors; D014665:Vasodilator Agents; D017311:Amlodipine; D000450:Aldosterone; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D003404:Creatinine; D011464:Epoprostenol; D012083:Renin; D007052:Ibuprofen