Prostacyclin and thromboxane biosynthesis in mild essential hypertension.
The possibility that prostacyclin or thromboxane biosynthesis is abnormal in patients with established mild essential hypertension was investigated in 46 patients. These eicosanoids have opposing effects both on vascular smooth muscle and on platelets. An imbalance in their biosynthesis could therefore influence both vascular tone and predisposition to thrombosis. We studied the relation between blood pressure and the biosynthesis of prostacyclin and thromboxane A2 by measuring urinary excretion rates of stable breakdown products of prostacyclin (6-oxo-prostaglandin F1 alpha and 2,3-dinor-6-oxo-prostaglandin F1 alpha) and of thromboxane A2 (thromboxane B2 and 2,3-dinor-thromboxane B2) using immunoaffinity chromatography and gas chromatography/electron capture mass spectrometry. Excretion rates of both of the prostacyclin-derived products ranged from less than 5 to more than 100 ng/g creatinine; each was significantly negatively correlated with blood pressure (r = 0.36-0.45). A reduction of 2,3-dinor-6-oxo-prostaglandin F1 alpha excretion of 100 ng/g creatinine was associated with an increase in arterial pressure of 14 mm Hg (systolic) and 8 mm Hg (diastolic) in patients who had been without antihypertensive medication for 2 weeks. The same reduction in 6-oxo-prostaglandin F1 alpha excretion was associated with an increased pressure of 19 mm Hg (systolic) and 12 mm Hg (diastolic) (2p less than 0.05 for diastolic pressure and 2p less than 0.01 for systolic pressure in each case). There were similar correlations between the excretion rates of these products and blood pressure in the same patients while they were receiving antihypertensive therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Minuz
P
P
Department of Clinical Pharmacology, Royal Postgraduate Medical School, Hammersmith Hospital, London, England.
Barrow
S E
SE
Cockcroft
J R
JR
Ritter
J M
JM
D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure; D015777:Eicosanoids / Q000652:urine*; D004573:Electrolytes / Q000652:urine; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology / Q000652:urine; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D013931:Thromboxanes / Q000096:biosynthesis*
D000959:Antihypertensive Agents; D015777:Eicosanoids; D004573:Electrolytes; D013931:Thromboxanes; D011464:Epoprostenol