Mechanisms of vasodilation elicited by VIP in sterically stabilized liposomes in vivo.
The purpose of this study was to begin to determine the mechanisms underlying vasodilation elicited by vasoactive intestinal peptide (VIP) in sterically stabilized liposomes (SSL) in the in situ peripheral microcirculation. Using intravital microscopy, we found that suffusion of VIP in SSL (0.42 and 0.85 nmol) onto the hamster cheek pouch for 1 h elicited significant and prolonged concentration-dependent vasodilation (P < 0.05). Suffusion of VIP in SSL (0.1 nmol) for 7 min elicited a qualitatively similar response, although its magnitude was significantly smaller than that elicited by 1 h of suffusion of VIP in SSL (P < 0.05). The VIP-receptor antagonist VIP-(10-28), but not the amino-terminal fragment VIP-(1-12), significantly attenuated and delayed the onset of VIP in SSL-induced vasodilation (P < 0.05). The nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), but not NG-nitro-D-arginine methyl ester (D-NAME), abrogated VIP in SSL-induced responses. We conclude that VIP in SSL elicits significant and prolonged vasodilation in the in situ peripheral microcirculation, which is specific, partly receptor dependent, and partly transduced by the L-arginine/NO biosynthetic pathway.
Séjourné
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Department of Pharmaceutics and Pharmacodynamics, University of Illinois at Chicago, USA.
Suzuki
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Alkan-Onyüksel
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Gao
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Ikezaki
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Rubinstein
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D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D002610:Cheek; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D006801:Humans; D008081:Liposomes; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D004337:Drug Carriers; D008081:Liposomes; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C056384:vasoactive intestinal peptide (1-12); D014660:Vasoactive Intestinal Peptide; C047945:vasoactive intestinal peptide (10-28); C010942:1,2-distearoyllecithin