Prostacyclin biosynthesis in essential hypertension before and during treatment.
Protacyclin biosynthesis was investigated in 133 untreated newly diagnosed patients with uncomplicated essential hypertension. Urinary excretion of 6-oxo-prostaglandin F1 alpha and of 2,3-dinor-6-oxo-prostaglandin F1 alpha, stable breakdown products of prostacyclin, was measured following a 1 month run-in period. To determine whether lowering blood pressure (BP) influenced prostacyclin biosynthesis, 106 consenting patients with diastolic pressure 90-120 mm Hg were allocated randomly to treatment with bendrofluazide, metoprolol, quinapril or amlodipine in an open parallel group design. Dose was increased to reduce diastolic arterial pressure to <90 mm Hg. Terazosin was added if this target BP was not achieved, and its dose increased if necessary. Urinary excretion rates of prostaglandins were measured after 1 year in patients in whom the target diastolic pressure was achieved. Mean arterial pressure varied from 106-168 mm Hg in untreated patients and excretion of both prostacyclin-derived products varied from <5 to >350 ng/g creatinine. Arterial pressure and prostaglandin excretion were not significantly correlated. In 57 patients in whom target pressure was achieved, BP before treatment was 166 +/- 2/100 +/- 1 at baseline and 144 +/- 2/86 +/- 1 mm Hg at 1 year. Excretion rates of each prostacyclin-derived product were similar before treatment and at 1 year, with no significant differences between the drugs. These findings do not support the hypothesis that deficient prostacyclin biosynthesis contributes to the pathogenesis of essential hypertension, or that increased prostacyclin biosynthesis plays a part in the response to treatment with antihypertensive medication.
Ritter
J M
JM
Department of Clinical Pharmacology, UMDS, Guy's Hospital, London, UK.
Brett
S E
SE
Woods
J D
JD
Benjamin
N
N
Stratton
P D
PD
Barrow
S E
SE
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives / Q000652:urine; D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001539:Bendroflumethiazide / Q000627:therapeutic use; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D007546:Isoquinolines / Q000627:therapeutic use; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use; D008875:Middle Aged; D000077583:Quinapril; D044005:Tetrahydroisoquinolines; D013928:Thromboxane A2 / Q000378:metabolism; D013929:Thromboxane B2 / Q000652:urine
D000959:Antihypertensive Agents; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D017311:Amlodipine; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D001539:Bendroflumethiazide; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; D011464:Epoprostenol; D008790:Metoprolol; D000077583:Quinapril