Converting enzyme inhibitors and their effects on the renin-angiotensin system of the blood vessel wall.
A local vascular tissue renin-angiotensin system (RAS) may contribute to blood pressure control and the maintenance of high blood pressure in some forms of hypertension, independently of the plasma RAS. Vascular converting enzyme (CE), present mainly in the endothelial layer of arteries and veins, can be altered in hypertension. Locally generated vascular angiotensin II (ANG II) may exert a number of actions on vascular tone and function, including directly and sympathetically mediated vasoconstriction, changes in vascular compliance in larger vessels, influence on vascular reactions to inflammation and injury, and alterations in vascular texture. Orally administered CE inhibitors have been shown to block not only the plasma RAS but also CE in the vasculature, leading to decreased vascular ANG II concentrations and possibly to an accumulation of locally generated vasodilator peptides and prostaglandins in the vascular wall. In spontaneously hypertensive rats, the slow recovery of CE activity in the vasculature on drug withdrawal was more closely associated with the slow return of blood pressure to hypertensive levels than the fast recovery of the plasma RAS. These and other experimental data discussed in this article favor the hypothesis that local CE inhibition in the vascular wall of resistance vessels, large arteries and veins contributes to the beneficial therapeutic effects of CE inhibitors in cardiovascular disorders such as hypertension and congestive heart failure.
Unger
T
T
Department of Pharmacology, University of Heidelberg, F.R.G.
Gohlke
P
P
Ganten
D
D
Lang
R E
RE
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D012084:Renin-Angiotensin System / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors