[Reduction of the antihypertensive effects of enalapril by indomethacin. Its independence from renal sodium retention].
OBJECTIVE
To evaluate in hypertensive patients whether or not the sodium-retaining effects of indomethacin can explain the indomethacin-induced attenuation of enalapril antihypertensive effects.


METHODS
Randomized, single-blinded, placebo controlled study with a placebo phase (2 weeks) followed by enalapril 20 mg/d (4 weeks, once daily) and enalapril 20 mg + indomethacin 75 mg/d (1 week). Enalapril dose increased up to 40 mg/d if inadequate response to 20 mg.


METHODS
Twenty-four patients with mild-moderated hypertension, showing an adequate response to enalapril (20-40 mg/d).


METHODS
Blood pressure evaluated by "casual" methods and by 24-hour ambulatory blood pressure monitoring, measurement of 24-hour urinary sodium excretion and fractional excretion of sodium: at the end of placebo, enalapril and enalapril + indomethacin treatments. Determination of the correlations between the changes induced by indomethacin (when added to enalapril) on the blood pressure and on sodium excretion effects of enalapril.


RESULTS
Enalapril significantly reduced casual blood pressure (systolic/diastolic) by 33/18 mmHg and 24-hour blood pressure by 20/9 mmHg. When added to enalapril, indomethacin attenuated (by 50%) the antihypertensive effects of enalapril and significantly decreased the 24-hour (from 120 +/- 11 mmol to 106 +/- 10 mmol) and fractional excretion of sodium (from 1.11 +/- 0.09% to 0.75 +/- 0.06%). However, the indomethacin-induced attenuation of enalapril hypotensive effects did not correlate with indomethacin-induced changes of sodium excretion.


CONCLUSIONS
When indomethacin is administrated to hypertensive patients that are well controlled with enalapril, it produces a marked attenuation of enalapril hypotensive effects and produces sodium retention. However, the amount of the attenuation of the hypotensive effects of enalapril by indomethacin are completely independent of the amount of the indomethacin-induced sodium retention. These results suggest that the mechanisms involved in interaction between both drugs at the blood pressure domain are probably localized at an extra-renal level.
Polónia
J
J
Unidade de Farmacologia Clinica, Faculdade de Medicina do Porto, Hospital de S. Joäo do Porto.
Gama
G
G
Santos
A
A
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors*; D018592:Cross-Over Studies; D004656:Enalapril / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012964:Sodium / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D004656:Enalapril; D012964:Sodium; D007213:Indomethacin
Atenuacão dos efeitos anti-hipertensores do enalapril pela indometacina. Sua independência da retencão renal de sódio.