Interaction between an angiotensin converting enzyme inhibitor, perindopril, and a thiazide diuretic in the spontaneously hypertensive rat.
Fifty adult male spontaneously hypertensive rats were randomly allocated to receive daily oral treatment with placebo, hydrochlorothiazide (HCTZ 10 mg/kg) and three different dosages of perindopril (S9490-30.1, 0.3 and 1 mg/kg) administered alone or in combination with HCTZ for two eight-day treatment periods separated by a therapeutic washout period of 13 days. Effect of order of treatment was evaluated in rats receiving perindopril plus HCTZ. Time course of changes in systolic blood pressure, heart rate, 24 h urine volume and urinary excretion of sodium, potassium and chloride were studied and compared for all groups. HCTZ alone and lower dosages of perindopril (0.1 mg/kg, 0.3 mg/kg) were ineffective in lowering elevated systolic blood pressure of the spontaneously hypertensive rat, and there were no significant intergroup differences in urine volume and electrolytes. However, antihypertensive efficacy of lower dosages of perindopril was significantly (P less than 0.01) enhanced when administered in combination with HCTZ. The combined treatment also induced significant (P less than 0.01) diuresis and urinary chloride excretion. No significant effect was seen in heart rate. The dose-effect relationship of the combination confirmed the existence of synergistic antihypertensive action between HCTZ and perindopril in the spontaneously hypertensive rat.
Scalbert
E
E
Institut de Recherches Internationales Servier, Tours, France.
Abdon
D
D
Devissaguet
M
M
Juggi
J S
JS
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004573:Electrolytes / Q000652:urine; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy*; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D020913:Perindopril; D051381:Rats; D011918:Rats, Inbred SHR; D014556:Urine
D000806:Angiotensin-Converting Enzyme Inhibitors; D004573:Electrolytes; D007211:Indoles; D006852:Hydrochlorothiazide; D020913:Perindopril