| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2808702 | Neuropeptides | 2006 | 7 Pages |
The present study investigated the potential role of vasoactive intestinal peptide (VIP) receptors, VPAC1 and VPAC2, in VIP-elicited coronary vasodilation of the isolated perfused rat heart. Additional studies determined the role of ATP-sensitive (KATP) and voltage-gated K+ (KV) channels in the VIP-elicited coronary vasodilation. Both the selective VPAC1 agonist, K15,R16,L27VIPl-7GRF8-27, and the selective VPAC2 agonist, RO25-1553, decreased coronary vascular resistance (CVR) in a dose-dependent manner, with EC50 values of 1.67 × 10−9 M and 7.11 × 10−9 M, respectively (VPAC1 vs VPAC2 agonist, P < 0.05). K15,R16,L27VIP1-7GRF8-27 and RO25-1553 maximally reduced CVR by −42 ± 4% and −39 ± 6% at 1 × 10−8 and 3 × 10−8 M, respectively. VIP at 1 × 10−10 M decreased CVR by −14 ± 2% in the absence (vehicle), by −11 ± 3% in the presence of the nonselective VIP receptor antagonist VIP10-28 (1 × 10−7 M; P > 0.05 vs. vehicle) and by only −4 ± 2% in the presence of the selective VPAC2 receptor antagonist PACAP6-38 (1 × 10−7 M; P < 0.05 vs. vehicle). In additional studies, VIP at 1 × 10−10 M decreased CVR by −22 ± 1% in the absence (control) and by only −10 ± 2% in the presence of the nonselective K+ channel blocker tetrabutylammonium (3 × 10−4 M; P < 0.05 vs. control). VIP reduced CVR by −4 ± 1% in the presence of the KATP channel blocker glibenclamide (3 × 10−6 M; P < 0.05 vs control) and by −28 ± 2% in the presence of the KV channel blocker 4-aminopyridine (3 × 10−4 M; P > 0.05 vs control). Thus, selective VPAC1 and VPAC2 receptor activation in the coronary circulation produces vasodilation and the VIP-elicited coronary vasodilation involves activation of VPAC2 receptors and KATP but not KV channels. In addition, VIP10-28 does not effectively block coronary vascular VIP receptors.
