Ex vivo and in vitro effects of trandolapril on the efflux of 22Na from the caudal artery of the SHR rat. Inhibition of vascular angiotensin II production

: The inhibition of converting enzyme (CE) activity in target tissues other than blood and lung vascular endothelium may be important for the antihypertensive action of CE inhibitors (ICE) (Unger et al 1983). In order to determine if ICE may have an effect on the transmembrane Na movements implicated in the regulation of vascular tone, we have studied the effects of trandolapril and enalapril on 22Na effluxes from the tail artery of 20 weeks old SHR. In vivo, the chronic oral treatment (14 days) with trandolapril (1.3 mg/kg/day) decreased the ouabain-sensitive 22Na efflux (controls: 0.050 +/- 0.004 min-1 (n = 8); trandolapril (1 mg/kg): 0.030 +/- 0.03 min-1 (n = 10) p less than 0.01), and the ouabain-insensitive 22Na efflux (controls: 0.088 +/- 0.0030 min-1; trandolapril (1 mg/kg): 0.080 +/- 0.003 min-1 (n = 10) p less than 0.05). Enalapril had no effect at the dose of 10 mg/kg/day (14 days). In vitro, trandolapril diacid (RU 44403) decreased the ouabain-sensitive 22Na efflux (controls: 0.045 +/- 0.002 min-1 (n = 6); RU 44403 (10(-9) M): 0.031 +/- 0.002 min-1 (n = 6) p less than 0.01), and the ouabain-insensitive efflux (controls: 0.096 +/- 0.004 min-1 (n = 6); RU 44403 (10(-9) M): 0.084 +/- 0.006 min-1 (n = 6) p less than 0.05). The effects were dose-dependent. Enalapril diacid (MK 422) also dose-dependently decreased 22Na effluxes but it was approximately 10 fold less active.(ABSTRACT TRUNCATED AT 250 WORDS)