Mechanisms of vasoactive intestinal peptide-elicited coronary vasodilation in the isolated perfused rat heart.
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.
Sawmiller
Darrell R
DR
Department of Internal Medicine/Cardiology, University of South Florida Health Science Center, Tampa, FL 33612-4799, USA. dsawmill@hsc.usf.edu
Ashtari
Mozhgan
M
Urueta
Hedy
H
Leschinsky
Melissa
M
Henning
Robert J
RJ
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D054086:KATP Channels; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D054086:KATP Channels; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; C092520:uK-ATP-1 potassium channel; D014660:Vasoactive Intestinal Peptide