Angiotensin II type-1 receptor antagonist, CS-866, reduces blood pressure without affecting glucose/insulin...

CS-866 is an angiotensin II type-1 receptor antagonist, the effects of which on systolic blood pressure (BP) and glucose/insulin metabolism are investigated under hyperlipidaemic conditions produced by cholesterol feeding. Thirty-two female Japanese White rabbits (two months old) were assigned randomly into a CS-866-treated group (n = 17) fed a food admixture that contained 0.03% CS-866 and 0.2% cholesterol, or into a control group (n = 15) fed a food admixture containing 0.2% cholesterol only. Systolic BP was measured by an ear-cuff method. Glucose and insulin metabolism was characterised quantitatively from the results of an intravenous glucose tolerance test by a minimal model technique reported previously. After six months treatment, systolic BP in the CS-866-treated group was lower than in the control group (105 +/- 14 mmHg versus 115 +/- 18 mmHg; P <0.05), as assessed by analysis of variance and the Wilcoxon rank-sum test. No significant differences were seen in plasma aldosterone concentration, plasma renin activity, or angiotensin-converting enzyme activity between the groups. Administration of CS-866 for six months did not affect either glucose tolerance or insulin sensitivity. Other model parameters such as basal (steady-state) insulin and glucose concentration, first- and second-phase post-hepatic insulin delivery to glucose, and insulin clearance rate constant were unaffected. In conclusion, CS-866 treatment reduced systolic BP without affecting glucose/insulin metabolism under hyperlipidaemic conditions produced by cholesterol feeding.