BLOOD-PRESSURE AND ENDOCRINE EFFECTS OF SINGLE DOSES OF CS-866, A NOVEL ANGIOTENSIN-II ANTAGONIST, IN SALT-RESTRICTED HYPERTENSIVE PATIENTS

Objective This study was conducted to assess the dose-response relatio nship of the new angiotensin II (Ang II) antagonist CS-866 on blood pr essure and on endocrine parameters in hypertensive patients with an ac tivated renin-angiotensin system. Design Following a four-way crossove r protocol, two groups of eight patients with mild-to-moderate hyperte nsion received a sodium-restricted diet (60 mmol daily) and ingested s ingle doses of 2.5, 10 and 40 mg or 5, 20 and 80 mg of CS-866, respect ively, or placebo. Twenty-four hour ambulatory blood pressure measurem ents, plasma renin activity (PRA), Ang II and concentrations of RNH-62 70, the pharmacologically active metabolite of CS-866, were monitored up to 24 h after medication. Results CS-866 was well tolerated. There was a significant decrease in 24 h diastolic blood pressure (DBP) at a ll doses of CS-866 above 5 mg. Increasing doses of CS-866 from 2.5 to 10 mg and from 5 to 20 mg lowered the mean 24 h DBP and DBP AUC(0-24h) values considerably more than increasing doses from 10 to 40 mg and f rom 20 to 80 mg, respectively. The mean 24 h DBP was lowered by 6.9 an d 8.4 mmHg after oral doses of 10 and 20 mg CS-866, respectively, comp ared with placebo and by 8.9 mmHg after 80 mg CS-866. The drug increas ed PRA and Ang II concentrations in plasma, maximum concentrations of which occurred within 3 h post-dose. The highest RNH-6270 concentratio ns were also found at the first post-dose measurement 3 h after admini stration of CS-866. Conclusion The new Ang II receptor antagonist CS-8 66 is effective and well tolerated. In salt-restricted hypertensive pa tients, CS-866 lowered blood pressure and increased PRA and Ang II con centrations at low doses. A single oral dose of 10-20 mg CS-866 result ed in almost maximal effects. (C) Rapid Science Publishers ISSN 0263-6 352.