Kinin- and non-kinin-mediated interactions of converting enzyme inhibitors with vasoactive hormones.
The antihypertensive effect of inhibitors of the angiotensin I-converting enzyme (ACE = kininase II) results from their vasodilatory and natriuretic effects as well as their effect on baroreceptor function. In addition to the inhibition of systemic and local angiotensin II formation, other local hormonal systems may also be involved in this effect at multiple target sites. Thus, potentiation of the vasodilator and natriuretic kinin system following inhibition of kininase II is thought to contribute to the persistent hypotensive effect of ACE inhibitors despite normalization of circulating ACE activity. Although increased plasma bradykinin levels cannot be detected, we found that the enhanced kinin-dependent local vascular prostacyclin production can be blunted in vitro by aprotinin, a kallikrein inhibitor. ACE inhibition may affect the atrial natriuretic peptide (ANP) system as the renin-angiotensin system and ANP appear to play antagonistic roles at the peripheral and central nervous system levels. Inhibition of kallikrein or of kininase II were both shown to modulate the natriuretic and vasorelaxant effects of ANP. In hypertensive subjects, we found that ACE inhibition with blood pressure normalization reduces basal and stimulated plasma ANP and blunts the renal sodium excretion in response to saline loading. In contrast, we did not observe effects of acute ACE inhibition in healthy sodium-depleted volunteers on plasma vasopressin under basal conditions or in response to passive tilt. Finally, we investigated the interaction of ACE inhibition with substance P, a powerful endogenous diuretic and natriuretic peptide that may have a transmitter function in the baroreceptor reflex arch.(ABSTRACT TRUNCATED AT 250 WORDS)
Medizinische Poliklinik, University of Bonn, F.R.G.
H J
HJ
Kramer
K
K
Glänzer
H
H
Meyer-Lehnert
M
M
Mohaupt
H G
HG
Predel
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000502:physiology; D006728:Hormones / Q000502:physiology*; D006801:Humans; D007705:Kinins / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology; D013373:Substance P / Q000502:physiology; D014667:Vasopressins / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D006728:Hormones; D007705:Kinins; D011453:Prostaglandins; D014667:Vasopressins; D013373:Substance P; D009320:Atrial Natriuretic Factor