Influence of non-steroidal anti-inflammatory drugs on renal function and 24h ambulatory blood pressure-reducing effects of enalapril and nifedipine gastrointestinal therapeutic system in hypertensive patients.
OBJECTIVE
To evaluate the influence of non-steroidal anti-inflammatory drugs (NSAIDs; aspirin and indomethacin) on the renal and antihypertensive effects of enalapril and nifedipine gastrointestinal therapeutic system (GITS) in patients with essential hypertension.


METHODS
In a crossover study, 18 patients on an unrestricted-salt diet were randomly assigned to receive either enalapril (20-40 mg/day) or nifedipine-GITS (30-60 mg/day) for 4-8 weeks, followed by aspirin (100 mg/day for 2 weeks) and then indomethacin (75 mg/day for 1 week). Blood pressure was measured by 24h ambulatory monitoring.


RESULTS
Enalapril and nifedipine-GITS significantly reduced blood pressure compared with placebo. Aspirin did not alter the antihypertensive effect of either drug. Indomethacin attenuated (by 45%) the antihypertensive effect of enalapril throughout the 24h period of evaluation, but did not interfere with the effect of nifedipine. Furthermore, indomethacin significantly reduced the fractional excretion of sodium and plasma levels of prostaglandins in a similar way when added to either the enalapril or the nifedipine regimen.


CONCLUSIONS
Vasodilatory prostaglandins are probably involved in the antihypertensive effects of enalapril but not of nifedipine, and this interaction seems to be independent of any indomethacin-induced decrease in renal sodium excretion. Nifedipine may be an appropriate drug to treat hypertensive patients requiring concomitant therapy with NSAID.
Polónia
J
J
Clinical Pharmacology Unit, Institute of Pharmacology and Therapeutics, Faculty of Medicine, Hospital de S. João, Porto, Portugal.
Boaventura
I
I
Gama
G
G
Camões
I
I
Bernardo
F
F
Andrade
P
P
Nunes
J P
JP
Brandão
F
F
Cerqueira-Gomes
M
M
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D018592:Cross-Over Studies; D004347:Drug Interactions; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004656:Enalapril; D009543:Nifedipine