Soluble pepstatins: a new approach to blockade in vivo of the renin-angiotensin system.

1. Synthesis of several pepstatin A derivatives was performed with the aim of increasing water solubility without altering the capacity to inhibit the renin-angiotensinogen reaction. 2. Pepstatinyl-arginine-O-methyl ester was studied in vitro and in vivo and compared with pepstatin A and with the arginine salt of pepstatin A. 3. This compound inhibited in vitro the reaction between purified hog renin and the synthetic renin N-acetyl-tetradecapeptide or the natural rat renin substrate. The inhibitory constant was of the same order of magnitude as that of pepstatin A. 4. In renal hypertensive rats, the bolus injection of pepstatinyl-arginine-O-methyl-ester or of the arginine salt of pepstatin decreased blood pressure to the same extent as a bolus injection of Sar1, Ala8-angiotensin II.