Low dose indapamide plus perindopril combination effects on cardiovascularstructure and function in genetic hypertension

1. Although the fixed combination preparations of thiazide and angiotensin- converting enzyme inhibitor are gaining wide acceptance in clinical practic e, data on the basic pharmacology of the combinations are relatively limite d. The long-term structural and functional effects of a fixed low dose (0.2 4 +/- 0.76 mg/kg per day) combination of indapamide + perindopril (I + P, S 5590) in spontaneously hypertensive rats (SHR) were examined in the present study. 2. Male SMR (10-12 weeks) were treated with I + P or vehicle for 8 weeks. T he blood pressure and heart rate were monitored by weekly measurements, At the end of the treatment period, left ventricular, aortic and intramyocardi al coronary arteriole structures were assessed. Contractile and relaxant pr operties of mesenteric arteries were determined by wire-myography. 3. Indapamide + perindopril combination caused a significant lowering of bo th systolic (P <0.001) and diastolic (P <0.001) blood pressures. Left ventr icle 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 re duced by I + P treatment. In contrast, the effect of I + P on intramyocardi al coronary vascular structure did not reach statistical significance. Ther e was some improvement in endotheliumin-dependent vasorelaxation of mesente ric vessels but contractile responses to noradrenaline and calcium were una ffected by treatment. 4. In summary, a low dose I + P combination treatment of SHR partly normali zes both systolic and diastolic blood pressures. Cardiac and larger vessel hypertrophy was reversed but intramyocardial coronary arteriole structure w as not as readily regressed by the end of the study.