INCREASED ARTERIAL DISTENSIBILITY INDUCED BY THE ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR, LISINOPRIL, IN NORMOTENSIVE RATS

1 We investigated possible structural correlates of the beneficial eff ect of chronic angiotensin-converting enzyme inhibition (ACEI) with li sinopril on the aortic distensibility of normotensive rats. 2 Experime nts were performed in young (4-month old), normotensive, Wistar rats w hich received lisinopril in their drinking water (0.9 or 9 mg kg(-1) d ay(-1)) for 9 months. 3 Following ACEI treatment, rats were pithed and aortic pulse wave velocity was measured during the progressive rise i n mean arterial blood pressure produced by i.v. infusion of the alpha( 1)-adrenoceptor agonist, phenylephrine. The slope of the regression li ne relating aortic pulse wave velocity to mean arterial blood pressure was taken as an index of aortic distensibility. Following this, the a orta was fixed in situ at a normotensive pressure level and histomorph ometry was performed. We also measured the calcium content of the aort ic 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 dos e 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 Alth ough the lower dose of lisinopril did not lower blood pressure, it did improve aortic distensibility as revealed by a fall in the slope rela ting 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, a nd in low and high ACEI groups, respectively. 6 Lisinopril treatment d id not modify the calcium content, the internal and external diameters or the medial thickness of the aorta. Chronic ACEI did, however, incr ease the thickness of the medial elastic fibres (controls 3.55 +/- 0.0 5 mu m, low dose ACEI 4.05 +/- 0.15 mu m (P < 0.05), and high dose ACE I 4.18 +/- 0.15 mu m (P < 0.05)). 7 In conclusion, we would suggest th at ACEI treatment with a low dose of lisinopril can decrease aortic st iffness via a pressure-independent mechanism which possibly involves a n effect of ACEI on elastic fibres.