Acute and long-term dose-response study of quinapril on hormonal profile and tissue angiotensin-converting enzyme in Wistar rats.
Therapeutic response to angiotensin-converting enzyme (ACE) inhibitors was reported to be better related to tissular than to circulating levels of ACE inhibition, especially during chronic therapy. We studied the relations between plasma concentrations of angiotensin I (AI), plasma renin activity (PRA), angiotensin II (AII), and aldosterone (by radioimmunoassay, RIA) and levels of serum and tissue ACE activities during acute and chronic quinapril administration in rats. Forty-eight male Wistar rats received quinapril by gavage for either 1 day (n = 24) or 15 days (n = 24) at different doses (control, 0.1, 1, and 10 mg/kg/day; 6 rats at each dose). Plasma hormonal parameters, serum, and tissue (lung, heart, and aorta) ACE activities were measured 3 h after the last gavage. Significant dose-dependent inhibitions of serum and lung ACE during acute and chronic treatments were observed (p < 0.05). Degrees of serum and heart ACE inhibition (at 0.1 mg/kg/day) were significantly lower with chronic than with acute treatment (p < 0.05). Degree of inhibition in lung, which represents the main source of total ACE, was similar during acute and chronic treatments. Among plasma hormonal parameters, plasma AI was correlated to PRA and showed the best correlation with ACE inhibition. After logarithmic transformation, log AI was significantly correlated to ACE activity in lung during chronic treatment (r = -0.85, p < 0.05). This parameter may provide a useful index for ACE inhibitor dosage adjustment during chronic therapy.
Schaison
F H
FH
Laboratoire de Pharmacologie, Institut Fédératif de Recherche en Physiopathologie et Génétique Cardiovasculaire, Hôpital de la Pitié-Salpêtrière, Paris, France.
Fernando Ramirez-Gil
J
J
Ciferri
S
S
Bernard
M
M
Baudin
B
B
Mougenot
N
N
Carayon
A
A
Lechat
P
P
D000450:Aldosterone / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000809:Angiotensins / Q000097:blood*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D006321:Heart / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D000077583:Quinapril; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D044005:Tetrahydroisoquinolines; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000450:Aldosterone; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D000077583:Quinapril