Angiotensin II Upregulates the Expression of L‐type Calcium Channels, Inositol Trisphosphate Receptors and Ryanodine Receptors in Rat Mesenteric Vascular Bed

Abstract

In vitro effects of angiotensin II (Ang II) on the expression of CaV1.2 L-type voltage dependent calcium channel (L-VDCC), type 1 inositol 1, 4, 5 trisphosphate receptor (IP3R1) and ryanodine receptor (RyR) in mesenteric vascular beds of Sprague-Dawley rats were studied using Western blots. Ang II dose-dependently upregulated the protein expression of L-VDCC, IP3R1 and RyR in cultured mesenteric arterial beds within 24 h. These actions were not blocked by losartan or candesartan (AT1 receptor antagonists); instead, the upregulations of L-VDCC and RyR, but not IP3R1, by Ang II were blocked by PD 123,319 (an AT2 or AT1B receptor antagonist). The mRNA levels of these channels were not found to be increased by Ang II. The endothelium nitric oxide synthase (eNOS) inhibitor, L-NAME, exerted a similar upregulation of these channels, while the nitric oxide donor, sodium nitroprusside (SNP), downregulated these channels. After endothelium damage by 0.3% CHAPS, Ang II had no effects on any of these channels. The upregulations of these channels by Ang II were also abolished by the PKC inhibitor chelerythrine and by the NAD(P)H oxidase inhibitor diphenyleneiodonium (DPI). These results suggest that: Ang II upregulates L-VDCC, IP3R1 and RyR calcium release channels in the rat mesenteric bed, with effects on the L-VDCC and RyR mediated by PD 123,319-sensitive receptors (AT2 or AT1B); These actions were via posttranscriptional modulation of the channels; PKC, NAD(P)H oxidase-mediated oxidative stress and NO signaling pathways and the endothelium were involved in these actions. Supported by HL 63903.