Abstract 1309: Differential Expression Pattern of the R4 Subfamily of Regulator of G Protein Signaling Proteins May Regulate Angiotensin II-Mediated Arterial Contraction via Kv Channels
Regulators of G protein signaling (RGS) proteins modulate G protein-coupled receptor (GPCR) signaling by accelerating the hydrolysis of GTP to GDP by Gα 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 Gαq. 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 9 R4 subfamily members in CIA, AA, and IVC of SD rats (n=8). Transcript expression of RGS5, RGS4, RGS3, RGS16, and RGS8 was higher in AA than in TA. Consistent with our hypothesis, we found that force generation of de-endothelialized arterial rings measured by myograph showed a significantly higher contraction force in TA compared with AA responding to Ang II, whereas there was no significant differential force generation response to phenylephrine. 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 Gαq activity by RGS5 increases the expression of this 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.