Increased arterial distensibility induced by the angiotensin‐converting enzyme inhibitor, lisinopril, in normotensive rats

1 We investigated possible structural correlates of the beneficial effect of chronic angiotensin‐converting enzyme inhibition (ACEI) with lisinopril on the aortic distensibility of normotensive rats. 2 Experiments were performed in young (4‐month old), normotensive, Wistar rats which received lisinopril in their drinking water (0.9 or 9 mg kg−1 day−1) for 9 months. 3 Following ACEI treatment, rats were pithed and aortic pulse wave velocity was measured during the progressive rise in mean arterial blood pressure produced by i.v. infusion of the α1‐adrenoceptor agonist, phenylephrine. The slope of the regression line relating aortic pulse wave velocity to mean arterial blood pressure was taken as an index of aortic distensibility. Following this, the aorta was fixed in situ at a normotensive pressure level and histomorphometry was performed. We also measured the calcium content of the aortic wall by atomic absorption. 4 The lower dose of lisinopril failed to lower systolic arterial blood pressure (unanaesthetized rat) or mean arterial blood pressure (pithed rat). Chronic ACEI with the higher dose of lisinopril lowered both systolic arterial blood pressure (104 ± 6 mmHg, controls 133 ± 4 mmHg, unanaesthetized), and mean arterial blood pressure (27 ± 1 mmHg, controls 34 ± 2 mmHg, pithed). 5 Although the lower dose of lisinopril did not lower blood pressure, it did improve aortic distensibility as revealed by a fall in the slope relating aortic pulse wave velocity (Y) to mean arterial blood pressure (X). Values were 5.7 ± 0.7, 3.8 ± 0.6 and 2.7 ± 0.3 in controls, and in low and high ACEI groups, respectively. 6 Lisinopril treatment did not modify the calcium content, the internal and external diameters or the medial thickness of the aorta. Chronic ACEI did, however, increase the thickness of the medial elastic fibres (controls 3.55 ± 0.05 μm, low dose ACEI 4.05 ± 0.15 μm (P < 0.05), and high dose ACEI 4.18 ± 0.15 μm (P < 0.05)). 7 In conclusion, we would suggest that ACEI treatment with a low dose of lisinopril can decrease aortic stiffness via a pressure‐independent mechanism which possibly involves an effect of ACEI on elastic fibres.