Mediators of glucagon-like peptide 2-induced blood flow: responses in different vascular sites.
The aims of the present study were: to characterize the mechanisms of hemodynamic alterations induced by GLP-2, and, to compare the responses elicited in the superior mesenteric artery (SMA) to other vascular beds. Anesthetized rats were infused at the doses of 0.9, 2.3, 4.6 and 9.3 nmol/kg into the jugular vein for 60 min. Blood flow in the various arteries was measured by the ultrasonic transit time technique. Some animals were pretreated with indomethacin (5 mg/kg, ip), L-NAME (9, 18, 36 and 72 micromol/kg, iv), atropine sulfate (1-2 mg/kg, iv), CCK-1 and CCK-2 receptor antagonists (L-364,718 and L-365,260, 1 mg/kg, iv), exendin (9-39) amide (35 nmol/kg, iv) and lidocaine (74 micromol/kg, iv) prior to the infusion of GLP-2 (4.6 nmol/kg). In another group, capsaicin was applied either systematically (125 mg/kg, sc) or vagally (1 mg/rat). GLP-2 administration at all doses significantly increased the SMA blood flow throughout the experiments. GLP-2 (4.6 nmol/kg) infusion significantly increased blood flow of inferior mesenteric artery and carotid artery but not in any other vessel measured. Only the pretreatments with L-NAME and lidocaine were ineffective in preventing the GLP-2-induced responses. These results implicate that GLP-2-induced blood flow alterations are most significant in the SMA and are not mediated by prostaglandins, muscarinic, GLP-1 or CCK receptors. Our results also suggest that the stimulatory effect of GLP-2 on SMA blood flow is NO-dependent and mediated via intrinsic, non-cholinergic enteric neurons.
Deniz
Mustafa
M
Marmara University School of Medicine, Department of Physiology, 34668 Haydarpaşa, Istanbul, Turkey. mddeniz1@hotmail.com
Bozkurt
Ayhan
A
Kurtel
Hizir
H
D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects* / Q000502:physiology; D020109:Devazepide / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D053767:Glucagon-Like Peptide 2 / Q000008:administration & dosage / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007262:Infusions, Intravenous; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D001570:Benzodiazepinones; D053767:Glucagon-Like Peptide 2; D006727:Hormone Antagonists; D010446:Peptide Fragments; D010671:Phenylurea Compounds; C058121:L 365260; C083773:exendin (9-39); D001285:Atropine; D008012:Lidocaine; D020109:Devazepide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin