Mechanisms of vasoactive intestinal peptide-elicited coronary vasodilation in the isolated perfused rat heart

Neuropeptides. 2006 Oct;40(5):349-55. doi: 10.1016/j.npep.2006.07.004. Epub 2006 Oct 9.

Abstract

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 (K(ATP)) and voltage-gated K(+) (K(V)) 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 EC(50) values of 1.67x10(-9)M and 7.11x10(-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 1x10(-8) and 3x10(-8)M, respectively. VIP at 1x10(-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 (1x10(-7)M; P>0.05 vs. vehicle) and by only -4+/-2% in the presence of the selective VPAC2 receptor antagonist PACAP6-38 (1x10(-7)M; P<0.05 vs. vehicle). In additional studies, VIP at 1x10(-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 (3x10(-4)M; P<0.05 vs. control). VIP reduced CVR by -4+/-1% in the presence of the K(ATP) channel blocker glibenclamide (3x10(-6)M; P<0.05 vs control) and by -28+/-2% in the presence of the K(V) channel blocker 4-aminopyridine (3x10(-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 K(ATP) but not K(V) channels. In addition, VIP10-28 does not effectively block coronary vascular VIP receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Coronary Circulation / drug effects*
  • Coronary Vessels / drug effects*
  • Heart / drug effects*
  • In Vitro Techniques
  • KATP Channels
  • Male
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels, Inwardly Rectifying / drug effects
  • Potassium Channels, Voltage-Gated / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Vasoactive Intestinal Peptide, Type II / agonists
  • Receptors, Vasoactive Intestinal Peptide, Type II / antagonists & inhibitors
  • Receptors, Vasoactive Intestinal Peptide, Type II / genetics
  • Receptors, Vasoactive Intestinal Polypeptide, Type I / agonists
  • Receptors, Vasoactive Intestinal Polypeptide, Type I / antagonists & inhibitors
  • Receptors, Vasoactive Intestinal Polypeptide, Type I / genetics
  • Vasoactive Intestinal Peptide / pharmacology*
  • Vasodilation / drug effects*

Substances

  • KATP Channels
  • Potassium Channel Blockers
  • Potassium Channels, Inwardly Rectifying
  • Potassium Channels, Voltage-Gated
  • Receptors, Vasoactive Intestinal Peptide, Type II
  • Receptors, Vasoactive Intestinal Polypeptide, Type I
  • uK-ATP-1 potassium channel
  • Vasoactive Intestinal Peptide