Regulators of G protein signaling (RGS) proteins modulate G protein-coupled receptor (GPCR) signaling by accelerating the hydrolysis of GTP to GDP by G慣 proteins. In vascular smooth muscle cell (SMC), activation by angiotensin II (Ang II) decreases voltage-gated K+currents (IKv) and increases [Ca2+]i through the activation of G慣q. Ang II signaling varies regionally in the vasculature, however . Here, we tested the hypothesis that differential expression of R4 RGS proteins underlies heterogeneous Ang II signaling in thoracic aorta (TA), inferior vena cava (IVC), common iliac artery (CIA), and abdominal aorta (AA). We found that expression of RGS5 mRNA was the highest among the R4 subfamily members in SD rats (n=8). mRNA expression of RGS5, RGS4, RGS3, RGS16, and RGS8 was higher in AA than in TA. Consistent with our hypothesis, force generation of de-endothelialized arterial rings measured by myograph showed a higher contraction force in TA compared with AA responding to Ang II. Furthermore, our data indicate that IKv was smaller in TA (n=10) than in AA (n=9; p < 0.05) SMCs. Consistent with this, Kv1.5 mRNA expression was 2.5-fold (p<0.05) higher in AA than in TA media. Interestingly, overexpression of RGS5 in cultured rat arterial SMCs increased Kv1.2 channel protein expression, indicating that inhibition of basal G慣q activity by RGS5 increases the expression of Kv channel subunit. In conclusion, expression pattern of R4 RGS proteins in vessel segments may effect Ang II-mediated vascular contraction via regulation of Kv channel.