The pressor actions of noradrenaline and angiotension II in chronic autonomic failure treated with indomethacin.
1 Indomethacin treatment of postural hypotension in four patients with chronic autonomic failure increased their pressor supersensitivity to intravenous noradrenaline without causing fluid retention. 2 All patients were supersensitive to angiotensin II in spite of normal levels of plasma renin activity in the supine position and therefore (by inference) of angiotensin II. This suggests that in autonomic failure, the degree of angiotensin receptor occupancy by endogenous angiotensin II is not important in determining pressor sensitivity to exogenous angiotensin II. Indomethacin increased the pressor supersensitivity to angiotensin II in all patients. 3 Indomethacin treatment decreased supine plasma renin activity to 50% of the level present before indomethacin treatment. 4 Indomethacin increased the lying but not the standing blood pressure. The failure to raise the standing pressure may be the result of the additional postural stress overcoming any vasoconstriction resulting from the increased sensitivity of vascular receptors to noradrenaline. The decrease in plasma renin activity could also contribute to the failure of indomethacin to prevent a fall in blood pressure on standing. 5 In our patients the excretion of the main urinary metabolite (PGFM) of prostaglandin F2 alpha was higher than recorded previously in normal controls. During treatment with indomethacin, plasma indomethacin levels were in the range at which inhibition of prostaglandin synthesis occurs and the excretion of PGFM was decreased. 6 Indomethacin was not effective in the treatment of postural hypotension in these patients with autonomic failure.
D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000502:physiology*; D001342:Autonomic Nervous System Diseases / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D007024:Hypotension, Orthostatic / Q000188:drug therapy*; D007213:Indomethacin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000502:physiology*; D011311:Pressoreceptors / Q000187:drug effects; D011460:Prostaglandins F / Q000652:urine
D011460:Prostaglandins F; D000804:Angiotensin II; C019171:prostaglandin F-main urinary metabolite; D009638:Norepinephrine; D007213:Indomethacin