Duration of inhibition of local microvascular ACE in spontaneously hypertensive rats

To investigate in vivo the duration of inhibition of local angiotensin converting enzyme (ACE) in the microcirculation after a 2-week oral treatment by three different ACE inhibitors.

The local renin-angiotensin system was studied in the microcirculation of cremaster muscle in spontaneously hypertensive rats treated by gavage with equihypotensive doses of trandolapril (0.6 mg/kg per day), enalapril (10 mg/kg per day) and perindopril (2 mg/kg per day) for 2 weeks. Intravital microscopy was used in an original preparation of cremaster isolated from its normal blood supply and externally perfused with physiological solution, allowing exclusion of the circulating converting enzyme. Local ACE activity was estimated by measuring vasoconstriction in response to 0.01 and 0.1 nmol/ml angiotensin I in the arterioles studied and classified as being of second, third and fourth order (mean diameters 58 +/- 6, 30 +/- 4 and 15 +/- 1 mu m for the three orders, respectively).

No difference among the ACE inhibitors was found 3 h after the last dose. Conversely at 7, 24 and 48 h after the last dose, a significant difference was found among the ACE inhibitors, with ACE inhibitors being higher in rats treated with trandolapril than in the other two groups. In addition, a comparison with untreated spontaneously hypertensive rats showed that significant inhibition persisted 48 h after the last dose for trandolapril- and perindopril- but not enalapril-treated rats.

Large differences exist between the duration of inhibition of the microvascular ACE in vivo. At that level of the vascular system, trandolapril appeared to provide the greatest duration of inhibition among the three ACE inhibitors tested.