Activation of P2X receptors (P2XRs) in renal vascular smooth muscle cells (RVSMCs) mediates sympathetic control and autoregulation of renal circulation triggering RVSMC contraction via elevation of [Ca2+]i resulting from Ca2+ entry via P2XRs and voltage-gated Ca2+ channels, and ryanodine receptor (RyR)- and inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca2+ release from the sarcoplasmic reticulum (SR) [1]. We have recently demonstrated that attenuation of P2X-mediated [Ca2+]i transients in RVSMCs from spontaneously hypertensive rats (SHR) is caused by P2X1 downregulation and decrease in the SR Ca2+ load [2]. Here we analysed the mechanisms of the decrease in the SR Ca2+ load in primary hypertension by comparison of: (i) expression of genes encoding RyRs, IP3Rs and phospholipase C β (PLCβ) using real-time PCR analysis; (ii) basal PLCβ activity using myo-D-[3H]inositol-based measurements of IP3 turnover; (iii) rate the SR Ca2+ leak using confocal detection of spontaneous Ca2+-release events in fluo-3 loaded RVSMCs from SHRs and their normotensive control, Wistar Kyoto (WKY) rats. Data are presented as mean ± S.E.M. and compared using Student’s t-test. We found that in SHR RVSMCs Ryr2 and Plcb1 were upregulated 24.5±8.6- and 22±5.8-fold, respectively (p<0.01), while there was no significant difference in Itpr1 expression (p=0.166). The peak of αβ-meATP-induced[Ca2+]i transient was reduced in SHR RVSMCs (p<0.001) from 746±58 nM (WKY, n=76) to 270±23 nM (SHR, n=55). The peak of caffeine-induced [Ca2+]i transients was reduced in SHR RVSMCs (p<0.001) from 688±32 nM (WKY, n=47) to 246±19 nM (SHR, n=21). Ryanodine-sensitive fraction of αβ-meATP-induced response increased in SHR RVSMCs (p<0.01) from 19±4 % (WKY, n=7) to 42±5 % (SHR, n=8), while cyclopiazonic acid- or 2-APB-sensitive fractions remained unchanged (p=0.77 and p=0.818, respectively). Basal level of IP3 production increased in SHR RVSMCs 3.8 times (p< 0.001): [3H]inositol posphates’ counts per minute elevated from 42.5±2.7 (WKY, n=6) to 163.3±20.6 (SHR, n=3). Spontaneous Ca2+-release events induced by the SR Ca2+ overload were sensitive to both ryanodine and 2-APB and had 4.4 times higher frequency in SHR RVSMCs (p<0.001): 0.38±0.08 Hz (WKY, n=9) and 1.67±0.2 Hz (SHR, n=16). Rate of the SR Ca2+ leak (∑(ΔF/F0)×s-1) was 9 times higher (p<0.001) in SHR RVSMCs. Thus, increased expression and activity of RyR2 and PLCβ1 in SHR RVSMCs augments the SR Ca2+ leak leading to decrease of the SR Ca2+ load and P2XR-mediated signals and may impair sympathetically driven and autoregulatory responses in renal vasculature in hypertension.