Chronic Inhibition of Angiotensin Converting Enzyme Decreases Ca-Dependent Tone of Aorta in Hypertensive Rats

Long-term effects of a novel angiotensin converting enzyme (ACE) inhibitor, CS-622, on Ca-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 Ca caused much greater relaxation in aortas excised from control SHR than those from SHR treated with CS-622. Restoration of Ca 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 Ca 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 Ca 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 Ca permeability of vascular smooth muscle membrane in SHR and that the restoration of normal Ca permeability of vascular smooth muscles may underlie long-term antihypertensive action of ACE inhibitors. (Hypertension 1989; 13:582-588)