Significance of the vascular concentration of angiotensin II-receptor blockers on the mechanism of lowering blood pressure in spontaneously hypertensive rats

To clarify the hypotensive mechanism of angiotensin ii receptor-blockers (arbs),drug concentrations in plasma and vascular tissues were measured using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and imaging mass spectrometry. in spontaneously hypertensive rats,systolic blood pressure (sbp) was measured 2 and 24 h after administration of candesartan cilexetil (0.3,1,or 3 mg/kg) or azilsartan (0.3,1,or 3 mg/kg). sbp was similarly lowered 2 h after administration of azilsartan or candesartan cilexetil,but it was significantly lower in the azilsartan-treated group than in the candesartan cilexetil-treated group at 24 h. angiotensin ii-induced vascular contractions were similarly attenuated 2 h after administration of these drugs,and the contractions were significantly lower in the azilsartan-treated group at 24 h. although plasma concentration was significantly lower in the azilsartan-treated group at 24 h,vascular concentration of azilsartan was significantly greater than that of candesartan. significant correlations between sbp and vascular concentrations were observed both at 2 and 24 h,while no significant correlation was observed between plasma and vascular concentrations. in conclusion,the mechanism of arb-induced hypotension is likely to depend on vascular concentrations rather than plasma concentrations. © the japanese pharmacological society.