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Perindopril and indapamide reverse coronary microvascular remodelling and improve flow in arterial hypertension
Danilo Neglia1, Enza Fommei, Anabel Varela-Carver
1Fondazione G Monasterio CNR-Regione Toscana, Pisa, Italy.
Insights
Antihypertensive treatment with perindopril + indapamide improved myocardial blood flow in patients with arterial hypertension. This study in patients and rats showed that the medication reverses coronary microvascular remodelling and enhances blood flow.
Area of Science:
- Cardiology
- Hypertension Research
- Vascular Biology
Background:
- Arterial hypertension is linked to coronary microcirculation abnormalities.
- Left ventricular hypertrophy (LVH) is a common complication of hypertension.
- Understanding microvascular changes is crucial for effective hypertension management.
Purpose of the Study:
- To investigate if antihypertensive treatment can reverse coronary microvascular remodelling in hypertensive patients and animal models.
- To assess the impact of treatment on myocardial perfusion.
Main Methods:
- A translational study involving 20 hypertensive patients with LVH and spontaneously hypertensive rats.
- Patients received perindopril + indapamide for 6 months; rats received placebo or the same treatment for 8 weeks.
- Measurements included blood pressure, left ventricular mass index, myocardial blood flow, coronary flow, and arteriolar histomorphometry.
Main Results:
- Perindopril + indapamide significantly reduced blood pressure and LVH in patients, while increasing myocardial blood flow.
- In rats, the treatment lowered blood pressure and significantly improved hyperaemic coronary flow.
- Histomorphometry revealed reverse remodelling of intramural coronary arterioles in treated rats.
Conclusions:
- Perindopril + indapamide effectively reduces blood pressure and LVH in hypertensive patients.
- The treatment improves both resting and hyperaemic myocardial blood flow.
- Evidence suggests that improved coronary flow is due to reverse remodelling of the coronary microcirculation.
Objectives:
Patients and animal models of arterial hypertension are characterized by structural and functional abnormalities of the coronary microcirculation. Using a translational approach, we ascertained whether antihypertensive treatment can reverse microvascular remodelling and improve myocardial perfusion.
Methods:
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. In spontaneously hypertensive rats, blood pressure, coronary flow and histomorphometry of intramural coronary arterioles were measured after 8 weeks of treatment with placebo or perindopril + indapamide.
Results:
In patients, treatment 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/m; P < 0.01) while increasing baseline (0.69 ± 0.13 to 0.88 ± 0.36 ml/min per g; P < 0.05) and hyperaemic myocardial blood flow (1.42 ± 0.32 to 1.94 ± 0.99 ml/min per g; P < 0.05). In rats treated with perindopril + indapamide (n = 11), blood pressure was 93 ± 18/55 ± 18 mmHg compared to 215 ± 18/161 ± 17 mmHg in placebo (n = 6; P < 0.001), baseline flow was unchanged whilst hyperaemic coronary flow was 19.89 ± 3.50 vs. 12.15 ± 0.99 ml/min per g, respectively (P < 0.01). The medial area of intramural arterioles was 1613 ± 409 with perindopril + indapamide and 8118 ± 901 μm with placebo (P < 0.001).
Conclusion:
In patients with arterial hypertension and left ventricular hypertrophy, perindopril + indapamide reduced blood pressure and left ventricular mass index and improved resting and hyperaemic myocardial blood flow. Data in rats provide evidence that the improvement in coronary flow observed after treatment is due to reverse remodelling of intramural coronary arterioles and improved microvascular function.
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