Perindopril plus indapamide reverses coronary microvascular remodeling and improves flow in arterial hypertension

Using a translational approach, we ascertained whether antihypertensive treatment can reverse coronary microvascular remodeling and improve myocardial perfusion. In 20 hypertensive patients with left ventricular hypertrophy, blood pressure, left ventricular mass index and myocardial blood flow were measured at baseline and after 6 months of treatment with perindopril + indapamide (PI). In spontaneously hypertensive rats, blood pressure, coronary flow and histomorphometry of intramural coronary arterioles were measured after 8 weeks of treatment with placebo or PI. In patients, PI decreased blood pressure (161±10/96±5 to 136±12/81±6 mmHg; p<0.0001) and left ventricular mass index (93±16 to 85±17 g/m2; p<0.01) whilst increasing baseline (0.69±0.13 to 0.88±0.36 mLomin-1og-1; p<0.05) and hyperemic myocardial blood flow (1.42±0.32 to 1.94±0.99 mLomin-1og-1; p<0.05). In rats treated with PI (n=11) blood pressure was 93±18/55±18 compared to 215±18/161±17 mmHg in placebo (n=6; p<0.001) whilst hyperemic/baseline coronary flow was 3.97±1.15 and 1.91±0.19 (p<0.001) respectively. The medial area of intramural arterioles was 1613.3±409.8 with PI and 8118±901.8 ?m2 with placebo (p<0.001). In patients with arterial hypertension and left ventricular hypertrophy treatment with PI reduced blood pressure and left ventricular mass index and improved resting and hyperemic myocardial blood flow. Data in rats provide evidence that the improvement in coronary flow observed after treatment with PI is due to reverse remodeling of intramural coronary arterioles and improved microvascular function.