Abstract 14618: Cavbeta2a Overexpression in Smooth Muscle Causes Hypertension via Impairment of Acetylcholine-dependent Vascular Relaxation

Introduction: The L-type Calcium channel (Cav1.2) plays an important role in smooth muscle contraction (via providing Ca2+ for contraction and inducing Ca2+ release from the sarcoplasmic reticulum) and relaxation (via activating Ca2+-activated K+ channels). Therefore, it is unclear if enhancing Ca2+ influx through Cav1.2 into vascular smooth muscle cells will cause hypertension or hypotension and what the underlying mechanism is. Hypothesis: Increasing Ca2+ influx influx into smooth muscle cells causes hypertension through impairing arterial relaxation. Methods: A transgenic (TG) mouse model with smooth muscle cell specific (SM22-α promoter driven) overexpression of a splicing variant of Cavβ2 subunit, Cavβ2a, tagged with GFP was established and studied. Results: Immunostaining showed that Cavβ2a-GFP expressed in smooth muscle cells specifically in small arteries and the L-type Ca2+ current in smooth muscle cells from mesenteric arteries of TG mice was significantly increased (5.1±0.7pA/pF in TG, n=12 vs....