Chronic inhibition of angiotensin converting enzyme decreases Ca2+-dependent tone of aorta in hypertensive rats.

Long-term effects of a novel angiotensin converting enzyme (ACE) inhibitor, CS-622, on Ca2+-dependent tone in aortic smooth muscles of spontaneously hypertensive rats (SHR) were examined. CS-622 (3 or 10 mg/kg/day), when orally administered to SHR for 21 weeks, exhibited a dose-dependent antihypertensive action. In Krebs-Henseleit solution, removal of Ca2+ caused much greater relaxation in aortas excised from control SHR than those from SHR treated with CS-622. Restoration of Ca2+ from zero to 2.5 mM elicited a marked contraction in aortas from control SHR but only a small contraction in aortas from both CS-622-treated SHR and normotensive Wistar-Kyoto rats. These findings suggested that myogenic tone that resulted from increased Ca2+ permeability in aortas of SHR was suppressed by long-term treatment with CS-622. The aortic tone from the individual rats correlated well with systolic blood pressure in both CS-622-treated and control SHR. The exaggerated myogenic tone in aortas of SHR was attenuated in the medium containing nicardipine but was not altered in the presence of CS-622 diacid (active form of CS-622) at a concentration high enough to fully inhibit aortic ACE. The myogenic tone in normal Ca2+ concentration was not decreased in aortas excised from SHR treated with hydralazine (5 mg/kg/day) for 21 weeks. We conclude that after prolonged administration CS-622 reduced the high vascular tension resulting from increased Ca2+ permeability of vascular smooth muscle membrane in SHR and that the restoration of normal Ca2+ permeability of vascular smooth muscles may underlie long-term antihypertensive action of ACE inhibitors.