Evaluation of the potential interaction between NaCl and prostaglandin inhibition in elderly individuals with isolated systolic hypertension

Objective To evaluate whether prostaglandin inhibition with the non-steroid al anti-inflammatory drug (NSAID), indomethacin (I) interacts synergistical ly with different doses of salt (NaCl) in elevating systolic blood pressure (SBP). Design and methods This randomized, placebo-controlled, double-blind, cross over study examined the interaction between NaCl and the prostaglandin inhi bitor, I in 31 healthy elderly individuals with a mean age (+/-SD) of 68.7 +/- 5.7 years (range 61-85 years). Participants aged more than 60 years on a 140 mmol/day NaCl dose for 6 weeks were chosen with normal blood pressure [24-h SEP < 148 mmHg, diastolic blood pressure (DBP) < 85 mmHg on the Take da Ambulatory Blood Pressure Monitor (TABPM); n =15] and isolated systolic hypertension (ISH), [24-h SEP > 148 mmHg, 24-h DBP < 85 mmHg on TABPM; n = 16]. Exclusion criteria included uncontrolled hypertension (SBP > 220 mmHg and/or DBP > 110 mmHg), cardiac disease, creatinine clearance < 60 ml/min, dementia and recent cerebrovascular accident or secondary hypertension. A 2 x 2 Latin square design was structured using four treatment groups [low sa lt (NaCl = 90 mmol/day) + I placebo, high salt (NaCl = 240 mmol/day) + I pl acebo, low salt + I (25 mg three times daily) and high salt + I] for 2 week s each, balanced and interspersed with 2 week washout periods to minimize c arryover effects. Twenty-four hour SEP, DBP and heart rate were measured an d summarized using a moving interval averaging technique. The mean change i n 24-h SEP, DBP, heart rate, urinary Na+, K+, protein and creatinine, creat inine clearance and serum electrolytes were compared across treatments in t he total cohort and in ISH and control groups separately using ANCOVA (SAS) . Results In the total cohort, compared with low NaCl, chronic high NaCl incr eased mean SEP (5.76 mmHg; P = 0.0002) and DBP (3.36 mmHg; P = 0.002). Indo methacin significantly increased mean SEP (2.66 mmHg, P = 0.015) but not DB P (0.31 mmHg, P = 0.419). High salt and I were additive (SBP up arrow, DBP up arrow) but there was no interaction (P = 0.795 and P = 0.739, respective ly). Additionally, chronic high NaCl increased serum Na (P = 0.0001) and 24 -h urinary Na (P = 0.0001) as expected. Indomethacin significantly decrease d mean heart rate (P = 0.018). The effects of NaCl and I on SEP, DBP and he art rate were not modified by age, alcohol intake, serum K+, body mass inde x or treatment order. In the ISH group, NaCl dose significantly elevated SE P (9.87 mmHg; P = 0.0001) and DBP (5.26 mmHg, P = 0.006) but did not signif icantly alter blood pressure in the normotensive group. Indomethacin signif icantly elevated SEP (P = 0.03) in normotensive individuals but had no effe ct on blood pressure in the ISH group. Conclusions Chronic high salt diet elevated blood pressure more than I in t he total cohort of elderly individuals. No interaction was demonstrated and their effects were additive. In the ISH group, chronic high salt diet sign ificantly increased SEP and DBP while I failed to alter blood pressure. In the normotensive group, I,but not salt, elevated SEP. Patients with ISH are sensitive to the presser effect of NaCl but resistant to the presser effec t of prostaglandin inhibition in contrast to elderly normotensive control i ndividuals where the reverse was found. J Hypertens 1999, 17:1195-1202 (C) Lippincott Williams & Wilkins.