Low dose indapamide plus perindopril combination effects on cardiovascular structure and function in genetic hypertension.
1. Although the fixed combination preparations of thiazide and angiotensin-converting enzyme inhibitor are gaining wide acceptance in clinical practice, data on the basic pharmacology of the combinations are relatively limited. The long-term structural and functional effects of a fixed low dose (0.24 + 0.76 mg/kg per day) combination of indapamide + perindopril (I + P,S5590) is spontaneously hypertensive rats (SHR) were examined in the present study. 2. Male SHR (10-12 weeks) were treated with I + P or vehicle for 8 weeks. The blood pressure and heart rate were monitored by weekly measurements. At the end of the treatment period, left ventricular, aortic and intramyocardial coronary arteriole structures were assessed. Contractile and relaxant properties of mesenteric arteries were determined by wire-myography. 3. Indapamide + perindopril combination caused a significant lowering of both systolic (P < 0.001) and diastolic (P < 0.001) blood pressures. Left ventricle plus septum:bodyweight ratio (P < 0.001), aortic medial cross-sectional area (P < 0.05) and media:lumen ratios (P < 0.005) were all significantly reduced by I + P treatment. In contrast, the effect of I + P on intramyocardial coronary vascular structure did not reach statistical significance. There was some improvement in endothelium-independent vasorelaxation of mesenteric vessels but contractile responses to noradrenaline and calcium were unaffected by treatment. 4. In summary, a low dose I + P combination treatment of SHR partly normalizes both systolic and diastolic blood pressures. Cardiac and larger vessel hypertrophy was reversed but intramyocardial coronary arteriole structure was not as readily regressed by the end of the study.
Ibrahim
J
J
Department of Clinical Pharmacology, Imperial College School of Medicine, St Mary's Hospital, London, UK. j.ibrahim@bio.gla.ac.uk
Schachter
M
M
Hughes
A D
AD
Sever
P S
PS
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D004359:Drug Therapy, Combination; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D007190:Indapamide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D020913:Perindopril / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR
D000959:Antihypertensive Agents; D007190:Indapamide; D020913:Perindopril