Antihypertensive mechanism of an angiotensin converting enzyme inhibitor, SA446, in dogs.

Antihypertensive mechanisms of SA446, an angiotensin converting enzyme (ACE) inhibitor, were examined in dogs. In isolated dog pulmonary artery, SA446 inhibited the contractile response to angiotensin (Ang) I, but did not affect the response to Ang II. In conscious dogs, SA446 (1 mg/kg po) remarkably inhibited the pressor response to Ang I between 1 and 6 hr after the administration. In normotensive dogs, SA446 (30 mg/kg po) significantly lowered the arterial pressure 3 hr after administration, which recovered at 24 hr, while plasma ACE activity was apparently inhibited even at 24 hr. The antihypertensive effect of SA446 (5 mg/kg po) was more potent in 2-kidney, 1-clip renal hypertensive dogs than in normotensive dogs. SA446 (10(-9) - 10(-7) M) inhibited the ACE activities in arteries isolated from dogs in concentration-dependent fashion. These results suggest that the antihypertensive effect of SA446 is related, at least partially, to inhibition of ACE in the vascular wall.