Inositol 1,4,5-Trisphosphate (IP3) Receptor Up-regulation in Hypertension Is Associated with Sensitization of Ca2+ Release and Vascular Smooth Muscle Contractility

Abstract

Background:The role of the vascular IP 3 receptor (IP 3 R) in hypertension is unknown. Results: IP 3 R are up-regulated in vascular smooth muscle (VSM) in hypertension through the calcineurin-NFAT pathway. Conclusion: Up-regulated IP 3 R in VSM sensitize Ca 2ϩ release and enhance contraction. Significance: Up-regulated vascular IP 3 R may contribute to vascular resistance in hypertension.

Effects of Administration of Amlodipine and Lacidipine on Inflammation-Induced Bone Loss in the Ovariectomized Rat

“…Another study showed that absence of IP3 inhibited osteoblasts formation [39]. It was shown that IP3R can be up-regulated via Ltype calcium channels and this upregulation increased the stimulation of calcineurin and NFAT as well as osteoclast activation [40]. In our study, we suggest that amlodipine and lacidipine exert anti-osteoporotic effects by blockade of L-type calcium channels and both these are agents known to effect IP3R [41].…”

Calcium Channels in Vascular Smooth Muscle

“…For example, mesenteric VSM of ANG II-induced hypertensive mice and spontaneously hypertensive rats display elevated mRNA and protein levels of IP 3 R1 (Abou-Saleh et al, 2013). This increased expression was associated with sensitization of IP 3 R-mediated Ca 2+ release, resulting in augmented vasoconstriction in response to stimulation by vasoactive agents in ANG II-induced hypertensive mice.…”

Calcineurin-NFATc Regulates Type 2 Inositol 1,4,5-Trisphosphate Receptor (InsP3R2) Expression during Cardiac Remodeling

“…A recent study has shown that during hypertension InsP 3 R1 expression is activated in vascular smooth muscle cells in a NFATc-dependent manner (42). This increase in InsP 3 R1 sensitizes IP 3 -mediated Ca 2ϩ signaling.…”