AMLODIPINE AND HEMODYNAMIC-EFFECTS OF CYCLOOXYGENASE INHIBITION

1 The haemodynamic effects of calcium antagonists could depend at leas t in part on the activity of vasoactive prostanoids. 2 We set out to s tudy the effect of the cyclo-oxygenase inhibitor ibuprofen, 400 mg thr ee times daily for 3 days, by a randomised cross-over study vs placebo in 12 mild to moderate essential hypertensive patients who had been t reated for 1 month with amlodipine. 3 Blood pressure, heart rate and v ascular resistances in the upper limb (Doppler ultrasound) were measur ed. Plasma renin activity and urinary aldosterone, as well as indices of renal function, were evaluated. Urinary 2,3-dinor-6-keto-PGF(1 alph a) and 2,3-dinor-TXB(2), as well as 6-keto-PGF(1 alpha) and TXB(2), we re measured as indices of systemic and renal PGI(2) and TXA(2) synthes is. 4 Amlodipine normalised blood pressure and reduced upper limb vasc ular resistances; it did not affect urinary prostanoid excretion. Shor t-term combined administration of ibuprofen resulted in, by comparison with placebo, inhibition of systemic PGI(2) (-80.5 ng 24 h(-1), 95% C I -99.2, -61.4; P < 0.001) and TXA(2) (-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 r egional 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-electro lytic balance.5 The haemodynamic effects of amlodipine may be partiall y antagonised by ibuprofen, which mainly determines inhibition of extr arenal prostanoid synthesis. It is suggested that this antagonism is a ttributable not so much to a direct effect of the calcium antagonist o n prostacyclin synthesis as to an alteration in vascular tone, depende nt on prostacyclin and perhaps other vasodilatory prostanoids.