Zabicipril hydrochloride

The length density (Lv) of capillaries is known to be increased in the hearts of spontaneously hypertensive rats (SHR) after high-dosed but also after low-dosed subantihypertensive treatment with the ACE-inhibitor Ramipril administered in utero and post partum. Under the same conditions in the present study only high-dose Zabicipril caused an increase of capillary Lv. Under preventive ACE-inhibition in both high-dose groups Lv of myocardial arteries was significantly higher. In the low-dose groups Lv was not significantly increased. The increased arterial Lv in the high-dose-group may result from the avoidance of angiotensin II-induced overabundant growth of myocardial muscle-mass. Changes in collagen could not be found in any of the experimental groups.

The positioning of a nonocclusive silicone collar around the rabbit carotid artery results in the formation of a neointima under a morphologically continuous endothelium. We wished to determine whether oral treatment with angiotensin-converting enzyme (ACE) inhibitors prevents or retards intimal thickening and whether this is related to the blood pressure (BP) lowering effects of such drugs. Silicone collars were placed around the left carotid artery of 104 male New Zealand white rabbits for 14 days. The contralateral carotid artery was sham-operated. Three ACE inhibitors were administered from 7 days before collar placement until the end of the experiment: zabicipril (0, 0.03, 0.10, or 0.30 mg/kg/day), moexipril (0, 0.3, 1, or 3 mg/kg twice daily, b.i.d.), and enalapril (0 or 3 mg/kg/day). Each group consisted of 6-12 animals. BP and plasma ACE activity were measured in the nonanesthetized rabbits after 3-week treatment. To evaluate intimal thickening, we measured the cross-sectional area of intima and media. The positioning of the collar led to significant intimal thickening after 14 days. Although the ACE inhibitors decreased BP (zabicipril, 9, 16, 16%; moexipril, 10, 22, 31%; enalapril, 15%) and plasma ACE activity (zabicipril, 87, 88, 92%; moexipril, 79, 92, 93%; enalapril, 88%) significantly and dose dependently, they did not reduce intimal thickening or the cross-sectional area of the media. Angiotensin II does not play a dominant role in collar-induced intimal thickening in rabbits. Furthermore, reducing the BP of normotensive rabbits does not alter neointima formation in this model.