FIGURE 1.

Increased expression and functional contribution of vascular IP₃Rs in experimental hypertension. A, measurement of SBP at base line and after infusion of SAL or Ang II to establish AHT. SBP was recorded by tail cuff plethysmography at base line (day 0) and at 7 and 14 days after infusion. SBP was significantly increased in AHT compared with SAL mice at 7 and 14 days (n = 12). B, immunoblot analysis of IP₃R in lysates from mouse MA. Artery lysate from SAL (control) and AHT mice was added to each lane (3 animals/group). C, relative protein density after normalization to GAPDH shows that IP₃R1 immunoreactivity was 2.4-fold higher in MA of AHT compared with SAL mice (n = 6). D, quantitative mRNA expression reveals a 1.8-fold increase of IP₃R1 transcript in arteries of AHT compared with SAL mice (n = 4–6). Ct values were normalized to the Ct value of the amplification standard β-actin, which was similarly expressed between MA of SAL and AHT mice. E, representative traces showing changes in vessel diameter in response to increasing concentrations of PE (gray dots). Isolated second order MA from SAL and AHT mice were cannulated and pressurized to 60 mm Hg, and diameter was recorded on-line by edge detection. After washout (WO), PE-induced contractions were repeated in the presence of 2-APB (50 μm) (right). F, concentration-response curves to PE in MA from SAL and AHT mice in the presence (+2-APB) or absence of 2-APB. PE-induced contraction was enhanced in arteries of AHT mice (n = 8 and 6). PE-induced contraction was inhibited by 2-APB in MA from both SAL and AHT mice (n = 8 and 6). *, significant difference between SAL and AHT; @, significant difference between SAL and SAL+2-APB; #, significant difference between AHT and AHT+2-APB. G, arteries from AHT mice showed an increased 2-APB-sensitive component of PE-induced contraction compared with SAL mice (n = 6 and 8). The 2-APB-sensitive component was calculated by subtracting concentration-dependent contractions to PE obtained in the presence of 2-APB from those obtained in the absence of the blocker. Error bars, S.E. *, p ≤ 0.05.