TRP channels in airway smooth muscle as therapeutic targets

Cation channels are of fundamental importance in regulating the function of airway smooth cells especially bronchoconstriction in response to spasmogens, and are therefore key players in the pathogenesis of asthma. To date, the identity of these cation channels remains a mystery. However, the recently emerged transient receptor potential (TRP) cation channel family has provided several promising channel candidates. The identification of the key TRP channels involved in regulating airway smooth muscle contractility, and therefore airway tone, could provide new and exciting prospects for the development of novel therapies for the treatment of airway diseases such as asthma. © Springer-Verlag 2005

Twenty-four hour and early morning blood pressure control of olmesartan vs. ramipril in elderly hypertensive patients: pooled individual data analysis of two randomized, double-blind, parallel-group studies

OBJECTIVE: To assess the antihypertensive efficacy of olmesartan medoxomil and ramipril on 24-h ambulatory blood pressure (ABP) in elderly hypertensive patients by pooled data analysis of two studies with identical designs (one Italian, one European). METHODS: After a 2-week placebo wash-out 1453 elderly hypertensive patients (65-89 years; sitting office DBP 90-109 mmHg and/or sitting office SBP 140-179 mmHg) were randomized to a 12-week double-blind treatment with olmesartan medoxomil 10 mg or ramipril 2.5 mg once-daily, up-titrated (20 and 40 mg olmesartan medoxomil; 5 and 10 mg ramipril) after 2 and 6 weeks in patients without normalized office BP. 24-h ABP was recorded at randomization and after 12 weeks. RESULTS: In 715 patients with valid baseline and end-of-treatment recordings baseline-adjusted 24-h SBP and DBP reductions were greater with olmesartan medoxomil (n = 356) than with ramipril (n = 359) [between-treatment differences and 95% confidence interval (CI), SBP: 2.2 (3.8, 0.6), P = 0.006; DBP: 1.3 (2.2, 0.3), P = 0.009]. Olmesartan medoxomil showed larger BP reductions in the last 6 h from the dosing interval and higher smoothness indices than ramipril. Olmesartan medoxomil reduced the SBP morning rise [-2.8 (-4.9, -0.8) mmHg], whereas ramipril did not [+1.5 (-0.6, +3.6) mmHg; P = 0.004 between-treatments]. Five hundred and eighty-two patients with sustained hypertension (office and 24-h ambulatory hypertension) showed the largest antihypertensive effect, with between-treatment differences still in favor of olmesartan medoxomil [SBP: 2.1 (3.9, 0.4), P = 0.019; DBP: 1.2 (2.3, 0.1), P = 0.032]. CONCLUSIONS: Olmesartan medoxomil provides a more effective and sustained 24-h BP control than ramipril in elderly hypertensive patients, particularly in the hours farthest from last intak