PREVENTIVE EFFECT OF CHRONIC CONVERTING-ENZYME INHIBITION ON AORTIC STIFFENING INDUCED BY RENOVASCULAR HYPERTENSION IN CONSCIOUS DOGS

Objective: The aim was to assess the influence of the renin-angiotensi n system on the geometrical and elastic properties of the aorta in con scious dogs, using a model of renovascular hypertension, and to examin e the effects of inhibition of the system by the angiotensin convertin g enzyme inhibitor spirapril. Methods: The aortic elastic behaviour in response to renovascular hypertension was studied in 15 conscious dog s instrumented with a pressure microtransducer and a pair of ultrasoni c diameter dimension gauges in the upper descending thoracic aorta. Re novascular hypertension was induced by surgical occlusion of one renal artery and stenosis of the other. One day after renal surgery, dogs w ere randomly assigned to two groups receiving for two months either th e new angiotensin converting enzyme inhibitor spirapril (n=8) or a pla cebo capsule (n=7). The two groups of dogs were compared to a control group of normotensive dogs (n=7). After two months of treatment the el astic properties of the aorta were studied by computation of the beat to beat pressure-diameter hysteresis loops obtained during transient i ncrease of pressure induced by bolus doses of angiotensin. The aortic pressure-diameter (P-D) relationship, obtained over a wide range, was fitted by an exponential fit (P=alpha.e(betaD)), where beta is the sti ffness index. A decomposition of the P-D curve according to a biphasic model of the parallel arrangement of elastin and collagen enabled two pressure-diameter elastic moduli to be obtained, one representing the resistance to stretch at low pressure levels (elastic fibres and smoo th muscle), and the other representing the resistance to stretch at th e highest pressures (collagen fibres). Results: The pressure-diameter curve of the placebo group was shifted to the left compared to the cur ves of the control and spirapril groups, showing that renovascular hyp ertension was associated with isobaric reduction of aortic diameter. T he stiffness index beta was higher (p<0.05) in the placebo group [0.60 5(SD 0.304) mm-1] than in either the control group [0.362(0.126) mm-1] or the spirapril group [0.348(0.083) mm-1], suggesting that renovascu lar hypertension was associated with aortic stiffening. The biphasic a nalysis showed that the collagen pressure-diameter elastic modulus was unaffected by spirapril, wheras the elastin pressure-diameter elastic modulus was significantly reduced by converting enzyme inhibitor with respect to the placebo (p<0.05). Conclusions: Chronic converting enzy me inhibition by spirapril prevents the isobaric aortic diameter reduc tion induced by renovascular hypertension in conscious dogs and decrea ses aortic stiffness, in particular by changing the elastic behaviour of the elastin fibres rather than of the collagen fibres.