Functional role of local angiotensin-converting enzyme (ACE) in adrenal catecholamine secretion in vivo.
The aim of the present study was to investigate whether exogenous angiotensin I (AngI) is locally converted to angiotensin II (AngII), which in turn results in an increase in the adrenal catecholamine (CA) secretion in the adrenal gland in anesthetized dogs. Plasma CA concentrations in adrenal venous and aortic blood were determined by an HPLC-electrochemical method. Adrenal venous blood flow was measured by gravimetry. Local administration of AngI (0.0062 to 6.2 microg, 0.0096 to 9.6 microM) to the left adrenal gland resulted in significant increases in CA output in a dose-dependent manner. Following administration of 0.62 microg (0.96 microM) of AngI, adrenal epinephrine and norepinephrine outputs increased from 20.8+/-13.6 to 250.9+/-96.4 ng x min(-1) x g(-1) (p<0.05, n = 5) and from 2.8+/-1.7 to 29.6+/-11.1 ng x min(-1) x g(-1) (p<0.05, n = 5), respectively. From the same left adrenal gland, the output of AngII increased from -0.02+/-0.04 to 26.39+/-11.38 ng x min(-1) x g(-1) (p<0.05, n = 5), while plasma concentrations of AngII in aortic blood remained unchanged. In dogs receiving captopril (12.5 microg, 0.5 mM) 10 min prior to AngI, the net amounts of CA and AngII secreted during the first 3 min after AngI were diminished by about 80% (p<0.05, n = 5) compared with those obtained from the control group. There was a close correlation (r2 = 0.91, n = 6) between the net increases in AngII and CA outputs induced by AngI. The results indicate that the local angiotensin converting enzyme is functionally involved in regional AngII formation in the canine adrenal gland in vivo. The study suggests that AngII thus generated may play a role in the local regulation of adrenal CA secretion.
Yamaguchi
N
N
Groupe de Recherche sur le Système Nerveux Autonome, Faculté de Pharmacie, Université de Montréal, Canada. nobuharu.yamaguchi@umontreal.ca
Martineau
D
D
Lamouche
S
S
Briand
R
R
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000803:Angiotensin I / Q000378:metabolism* / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D002395:Catecholamines / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004837:Epinephrine / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000494:pharmacology / Q000502:physiology*; D013997:Time Factors
D002395:Catecholamines; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D009638:Norepinephrine; D004837:Epinephrine