Differential effects of sulindac and indomethacin on blood pressure in treated essential hypertensive subjects.
Attenuation of the effectiveness of antihypertensive therapy by non-steroidal anti-inflammatory (NSAI) drugs has been attributed to inhibition of systemic or renal vasodilator prostaglandin synthesis, or a combination of both. Indomethacin is a NSAI drug with both renal and extrarenal cyclo-oxygenase inhibition properties. Sulindac is a relatively selective cyclo-oxygenase inhibitor said not to affect urinary prostaglandin excretion. This study examines the relative effect on blood pressure of 4 weeks' treatment, with indomethacin 25 mg three times daily and sulindac 200 mg twice daily, in a randomized placebo controlled trial in 26 hypertensive subjects. In nine patients treated with indomethacin, supine blood pressure rose 11 mmHg systolic and 4 mmHg diastolic by the end of the first week, whereas nine subjects treated with sulindac showed a fall in blood pressure similar to the trend seen in placebo-treated subjects. Indomethacin treatment inhibited renal cyclo-oxygenase with a 78% reduction in urinary prostaglandin E2 excretion and 89% suppression of plasma renin activity. Neither measurement was affected by sulindac. Extrarenal cyclo-oxygenase activity was inhibited by both indomethacin and sulindac with serum thromboxane B2 decreasing by 96% and 69% respectively. The results suggest that the pressor effect of NSAI drugs is predominantly related to renal cyclo-oxygenase inhibition. the lack of effect of sulindac on blood pressure may make it a safer therapeutic option if NSAI drug therapy is necessary in the hypertensive patient.
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007192:Indenes / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism; D013467:Sulindac / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D007192:Indenes; D013467:Sulindac; D012964:Sodium; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin; D007213:Indomethacin