Liposomal VIP attenuates phenylephrine- and ANG II-induced vasoconstriction in vivo.
The purpose of this study was to determine whether vasoactive intestinal peptide (VIP) modulates vasoconstriction elicited by phenylephrine and ANG II in vivo and, if so, to begin to elucidate the mechanisms underlying this phenomenon. Using intravital microscopy, we found that suffusion of phenylephrine and ANG II elicits significant vasoconstriction in the in situ hamster cheek pouch that is potentiated by VIP-(10-28), a VIP receptor antagonist, but not by VIP-(1-12) (P < 0.05). Aqueous VIP has no significant effects on phenylephrine- and ANG II-induced vasoconstriction. However, VIP on sterically stabilized liposomes (SSL), a formulation where VIP assumes a predominantly alpha-helix conformation, significantly attenuates this response. Maximal effect is observed within 30 min and is no longer seen after 60 min. Empty SSL are inactive. Indomethacin has no significant effects on responses induced by VIP on SSL. The vasodilators ACh, nitroglycerin, calcium ionophore A-23187, 8-bromo-cAMP, and isoproterenol have no significant effects on phenylephrine- and ANG II-induced vasoconstriction. Collectively, these data suggest that vasoconstriction modulates VIP release in the in situ hamster cheek pouch and that alpha-helix VIP opposes alpha-adrenergic- and ANG II-induced vasoconstriction in this organ in a reversible, prostaglandin-, NO-, cGMP-, and cAMP-independent fashion.
Ikezaki
H
H
Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Onyüksel
H
H
Rubinstein
I
I
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D002610:Cheek; D006224:Cricetinae; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004337:Drug Carriers; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008081:Liposomes; D008297:Male; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000098:blood supply; D005996:Nitroglycerin / Q000494:pharmacology; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D004337:Drug Carriers; D008081:Liposomes; D014665:Vasodilator Agents; D000804:Angiotensin II; D010656:Phenylephrine; C016276:8-bromocyclic GMP; D014660:Vasoactive Intestinal Peptide; D000001:Calcimycin; D005996:Nitroglycerin; D006152:Cyclic GMP; D007545:Isoproterenol; D000109:Acetylcholine; D007213:Indomethacin