Inhibitory effect of telmisartan on the blood pressure response to angiotensin II challenge

Telmisartan is a new angiotensin receptor antagonist possessing potent, sel ective, and insurmountable inhibitory activity specific to the angiotensin II type 1 (AT(1)) receptor. The current study was performed to determine th e inhibition of the angiotensin II pressor response by telmisartan in 48 he althy volunteers challenged with hypertension-inducing doses of i.v. angiot ensin II. Subjects were challenged with this dose of angiotensin II at inte rvals between 0.25 and 48 It after double-blind single-dose oral administra tion of telmisartan 20 mg (n = 12), 40 mg (n = 12), or 80 mg (n = 12) or pl acebo (n = 12) in parallel groups. Diastolic and systolic blood pressure an d pulse rate were recorded continuously using a servophotoplethysmograph. U rine samples were collected during the study for urinalysis. Tolerability o f telmisartan, in comparison with placebo, was also monitored throughout th e study. Telmisartan 20-80 mg dose dependently inhibited the increase in di astolic and systolic blood pressure induced by angiotensin II. Telmisartan 40 mg produced 80.1 % maximum inhibition, and with 80 mg 89.6% maximum inhi bition of diastolic blood pressure was achieved. Inhibition was apparent af ter 0.3-1.1 It and was still observed 48 h after administration for all tel misartan doses. The inhibitory effect of telmisartan 20, 40, and 80 mg, 48 h after dosing was significantly greater than that of placebo. A > 25% inhi bition of the angiotensin II response on diastolic blood pressure was detec ted until 26.9, 35.4, and 40.5 h. respectively, after telmisartan 20 mg, 40 mg, and 80 mg. Anti-clockwise hysteresis was observed, indicating a delay and longer persistence of effect than to be expected from the plasma concen tration-time course. The slow dissociation of telmisartan from the receptor probably contributed to this hysteresis. The incidence of adverse events w as comparable in telmisartan- and placebo-treated subjects and was not dose dependent. In conclusion, telmisartan 40 mg provides rapid-onset, well-tol erated, and near-maximal inhibition of angiotensin II-induced hypertension, with maintenance of the inhibitory effect for 48 h.