Comparison of the relative importance of vascular and plasma drug concentrations to the hypotensive effect of telmisartan in rats

INTRODUCTION: To clarify the importance of the vascular concentration of an angiotensin II receptor blocker (ARB) to its hypotensive effect, the relationships between the drug concentrations in plasma and vascular tissues and the hypotensive effect after administration of an ARB were compared. MATERIALS AND METHODS: In spontaneously hypertensive/NDmcr-cp rats (SHR/NDmcr-cp), systolic blood pressure (SBP) and angiotensin II-induced vascular contraction were measured 2 h and 24 h after administration of telmisartan (3 mg/kg). Plasma and vascular concentrations of telmisartan were also measured at 2 h and 24 h. RESULTS: SBP was significantly lower 2 h after administration of telmisartan, and the significant hypotensive effect was continued until 24 h. A significant attenuation of angiotensin II-induced vascular contraction at 2 h was also continued until 24 h. No significant difference between 2 h and 24 h was observed both in SBP and angiotensin II-induced vascular contraction. Vascular concentration at 24 h was 90.0% when the concentration at 2 h was assumed to be 100%, and no significant difference was observed. However, the plasma concentration of telmisartan at 2 h was significantly decreased by 88.2% at 24 h. CONCLUSION: The vascular drug concentration, not the plasma drug concentration, may be related to the hypotensive effect after administration of telmisartan.