Misoprostol effects on diclofenac-induced cardiorenal changes in salt-sensitive patients with hypertension: the MEDIC Study.

摘要: Study Objective. To determine whether coadministration of misoprostol with the nonsteroidal antiinflammatory drug diclofenac lessens increase in blood pressure and improves alterations renal hemodynamics induced by diclofenac. Design. Prospective, randomized, double-blind, placebo-controlled, crossover study. Setting. Two university research centers. Patients. Nineteen senior (mean age 62 yrs [range 55–73 yrs]), salt-sensitive patients stage 1 or 2 hypertension. Intervention. After a 3-week antihypertensive withdrawal lead-in phase, received either 75 mg alone plus 200 μg twice/day for 14 days. 10-day washout period, alternate treatment. Measurements Main Results. Blood was measured 24-hour ambulatory monitoring, effective plasma flow (ERPF) rate determined para-aminohippurate clearance, glomerular filtration (GFR) iothalamate clearance. Mean arterial (MAP = diastolic + 0.33[systolic - pressure]) rate-pressure product (RPP systolic x heart 10−2) were also used to compare treatment groups. Diclofenac increased MAP mean ± SEM 5.0 1.0 mm Hg RPP 337 181 units compared baseline. The ERPF GFR decreased 40.5 26.9 ml/minute 14.1 6.5 ml/minute, respectively. diclofenac-induced 3.3 (95% confidence interval [CI] 1.1–5.3 Hg, p=0.004) 724 238 CI 225–1223 units, p=0.007). 56.1 35.0 −24.7–137.0 ml/min, p=0.15) 18.1 7.1 1.9–34.5 p=0.03). relatively well tolerated; no adverse effects reported misoprostol. Conclusion. In hypertension, attenuated elevation vasoconstrictive tolerated.