Role of calcitonin gene-related peptide and kinins in post-ischemic intestinal reperfusion.
The involvement of kinins, calcitonin gene-related peptide (CGRP), and tachykinins during mesenteric post-ischemic reperfusion was studied in anesthetized rats by using antagonists for bradykinin (BK) B1, BK B2, CGRP1, or tachykinin NK1 receptor, or by capsaicin-induced desensitization. B1, B2, or CGRP1 receptor antagonists or desensitization attenuated the transient hypotension and plasma protein and leukocyte infiltration of intestinal wall observed during post-ischemic reperfusion. These effects were abolished by the combination of B2 and CGRP1 blockade as well as by B2 antagonism in capsaicinized rats, while NK1 blockade was ineffective. Our results suggest that kinins and CGRP contribute to systemic vasodilatation and microvascular leakage during mesenteric reperfusion. Pharmacological blockade of these systems could help preventing hypotension and intestinal injury consequent to reperfusion.
Madeddu
P
P
Gene Therapy Section of the National Laboratory of the National Institute of Biostructures and Biosystems (I.N.B.B.) via Brigata Sassari, 13 07033, Osilo (Sassari), Italy.
Emanueli
C
C
Bonaria Salis
M
M
Franca Milia
A
A
Stacca
T
T
Carta
L
L
Pinna
A
A
Deiana
M
M
Gaspa
L
L
D000818:Animals; D065168:Bradykinin Receptor Antagonists; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D004386:Duodenum / Q000473:pathology; D007249:Inflammation / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism; D007705:Kinins / Q000502:physiology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D064729:Neurokinin-1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D015424:Reperfusion; D015427:Reperfusion Injury / Q000378:metabolism*; D015320:Tachykinins / Q000096:biosynthesis; D013997:Time Factors
D065168:Bradykinin Receptor Antagonists; D007705:Kinins; D064729:Neurokinin-1 Receptor Antagonists; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D015320:Tachykinins; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin