Effect of low doses of perindopril and indapamide alone or in combination (Preterax) in renovascular hypertensive rats

Left renal artery clipping and contralateral nephrectomy were performed in Wistar rats to induce renovascular hypertension (HT). HT rats for 4 weeks, received either a normal diet or perindopril (PER, 0.76 mg. kg(-1) . day(-1 )), or indapamide (IDP, 0.24 mg. kg(-1). day -') or Preterax (PER+IDP) at t he same doses. A normotensive (NT) control group received a normal diet. At the end of treatment, arterial pressure, cardiac output and systemic art erial compliance (SAC) were determined. Thoracic aorta histomorphometry all owed quantification of the structural characteristics of the arterial wall. Coronary microvessel densities (arterioles and capillaries) were evaluated by double immunolabelling and quantitative stereology in the left ventricu lar inner myocardium. Mean arterial pressure was higher in HT than in NT rats (174 +/- 11 vs 124 +/- 5 mmHg, P<0.01). Hypertension was prevented by PER alone and by PER+IDP . IDP alone did not significantly decrease blood pressure. SAC was decrease d by 59% in the HT compared with the NT group. All treatments restored SAC values to normal. Left ventricular hypertrophy (+76% in HT vs NT controls) was significantly reduced by IDP (-19%, P < 0.05) and prevented in the PER and Preterax groups. The thoracic aorta media was thicker in the HT than in the NT group (by 49%, P < 0.001) in association with smooth muscle cell hy pertrophy (by 73%, P < 0.001). Treatment with PER and Preterax decreased me dia thickness by 25% and 32% respectively (P < 0.001) and smooth muscle hyp ertrophy by 29% and 30% (P < 0.01). IDP alone had no significant effect on media thickness and hypertrophy. Treatment with PER alone prevented the inc rease in arteriolar density but did not significantly affect the low corona ry capillary density observed in untreated hypertensive rats. In contrast, treatment with IDP alone preserved normal capillary myocardial density but did not significantly affect the arteriolar density. The combination of bot h drugs resulted in normal levels of arteriolar and capillary myocardial de nsities. Goldblatt 1 kidney, 1 clip rats exhibit severe hypertension and left ventri cular hypertrophy. IDP alone did not significantly affect key haemodynamic parameters; however, it decreased cardiac hypertrophy and restored SAG. PER alone normalized haemodynamics and structure. Furthermore, IDP could have beneficial effects on myocardial capillary density. The combination of IDP and PER had additional effects and prevented the increase in blood pressure , cardiac weight and aortic wall hypertrophy. Furthermore, treatment with P reterax reversed microvascular alterations, specifically arteriolar and cap illary densities.