Central effects of converting enzyme inhibitors.
Evidence has accumulated that systemic administration of converting enzyme inhibitors (CEI) such as captopril, MK 421 or SA 446 not only produces an inhibition of the plasma renin angiotensin system (RAS), but also of the RAS in various target organs which are relevant for blood pressure (BP) regulation. A potential target organ is the brain, where a local CE inhibition could contribute to the BP lowering action of CEI. CE in the brain can be inhibited by intracerebroventricular (i.c.v.) injection of CEI as evidenced by an inhibition of the pressor and drinking responses to i.c.v. angiotensin I (ANG I) or renin and by potentiation of the pressor responses to i.c.v. bradykinin. Site of the inhibition is not only the cerebrospinal fluid but also periventricular brain tissue such as the hypothalamus. I.c.v. injection of captopril at doses which inhibit brain CE but do not leak into the peripheral blood were shown to lower BP in conscious stroke-prone spontaneously hypertensive rats (SHRSP), but not in normotensive Wistar Kyoto (WKY) controls. Acute peripheral administration of CEI can produce an inhibition of brain CE. This was shown by an attenuation of the drinking responses to i.c.v. ANG I and renin and by direct measurements of CE activity in brain tissue. Chronic oral treatment with CEI produces changes of brain RAS parameters which suggest an inhibition of ANG II formation in the brain.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007276:Injections, Intraventricular; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D012083:Renin