Perindopril and indapamide reverse coronary microvascular remodelling and improve flow in arterial hypertension.
OBJECTIVE
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).


CONCLUSIONS
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.
Fondazione G Monasterio CNR-Regione Toscana, Pisa, Italy.
Danilo
D
Neglia
Enza
E
Fommei
Anabel
A
Varela-Carver
Massimiliano
M
Mancini
Sergio
S
Ghione
Massimo
M
Lombardi
Patrizia
P
Pisani
Howard
H
Parker
Giulia
G
D'amati
Luigi
L
Donato
Paolo G
PG
Camici
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D001783:Blood Flow Velocity / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007190:Indapamide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007190:Indapamide; D020913:Perindopril