Kinetic studies of the pharmacologic response to captopril in rats. I. Role of the renin-angiotensin system.
Pressor response to exogenous angiotensins was investigated in rats. Two-kidney Goldblatt hypertensive rats (GHR) and sodium-deficient normotensive rats (SDR), as well as normal rats, (NR) were used. Various amounts of angiotensin I (Ang I) or angiotensin (Ang II) were administered intravenously by constant infusion, with or without pretreatment with angiotensin converting enzyme (ACE) inhibitor, and the pressor response was determined. Captopril was used as the ACE inhibitor. From the data obtained, a simple kinetic model for the renin-angiotensin system was constructed. The model was based on a linear compartment model with the following assumptions; (a) there are compartments in respect to Ang I and II in the body; (b) in the steady-state condition, Ang I is produced at a constant rate; (c) a part of Ang I is converted to Ang II by a first-order rate process; (d) Ang I and II are eliminated from the respective compartments by first-order rate processes and (e) the relationship between mean arterial blood pressure and the amount of Ang II in the body can be described by Hill's equation with a baseline effect. Then the pressor response to angiotensins in GHR, SDR or NR was fitted to the model. The result indicated that the pressor response to Ang I or Ang II can be described by the present model. The model parameters obtained were consistent with the actual physiological parameters of rats.
Endoh
M
M
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Suzuki
M
M
Katayama
K
K
Kakemi
M
M
Koizumi
T
T
D000803:Angiotensin I / Q000097:blood / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006978:Hypertension, Renovascular / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012964:Sodium / Q000172:deficiency
D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D012964:Sodium; D007703:Peptidyl-Dipeptidase A; D012083:Renin