Effects of calcitonin gene-related peptide on canine cerebral artery strips and the in-vivo vertebral blood flow in dogs

1989 ◽  
Vol 340 (4) ◽  
pp. 431-436 ◽  
Author(s):  
Ichiro Ikegaki ◽  
Yoshio Suzuki ◽  
Shin-ichi Satoh ◽  
Toshio Asano ◽  
Masato Shibuya ◽  
...  
1989 ◽  
Vol 9 (3) ◽  
pp. 268-270 ◽  
Author(s):  
Yoshio Suzuki ◽  
Shin-Ichi Satoh ◽  
Ichiro Ikegaki ◽  
Tomohisa Okada ◽  
Masato Shibuya ◽  
...  

The effects of neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) on local cerebral blood flow (LCBF) were studied in vivo in rat striatum. Administration of 1 and 5 nmol NPY as a bolus into the internal carotid artery caused a dose-dependent decrease in the ipsilateral striatal LCBF. This decrease developed slowly and persisted for at least 2 h, without affecting mean blood pressure. In contrast, CGRP, at a concentration of 10 pmol, increased striatal LCBF by about 30%, and the duration of the increase was about 1 h. However, at higher doses of CGRP no increase in LCBF was observed. These results suggest that NPY and CGRP released from nerve fibers innervating blood vessels can function as long-acting modulators of CBF.


1995 ◽  
Vol 89 (6) ◽  
pp. 565-573 ◽  
Author(s):  
Keith K. C. Tan ◽  
Morris J. Brown ◽  
Richard J. Hargreaves ◽  
Sara L. Shepheard ◽  
Deborah A. Cook ◽  
...  

1. Calcitonin gene-related peptide (CGRP) is localized in perivascular sensory neurons and is a potent vasodilator. We investigated the utility of immunoblockade as an in vivo technique for probing the role of CGRP as an endogenous vasodilator. 2. The effects of an anti-CGRP monoclonal antibody (MAb; coded C4.19) and its Fab′ fragment on CGRP-induced changes in blood pressure and skin blood flow were studied in pentobarbitone-anaesthetized rats. Antidromic skin vasodilatation in the rat hind paw was measured by laser Doppler fluxmetry. 3. The dose—response relationship for the hypotensive effect of intravenous rat αCGRP (rαCGRP) was similarly shifted rightward by MAb C4.19 IgG (1 mg/rat; intravenously) and Fab′ fragment (2 mg/rat; intravenously). The C-terminal fragment of human αCGRP (hαCGRP8–37) also blocked the hypotensive effect of rαCGRP. 4. MAb C4.19 Fab′ fragment (2 mg/rat; intravenously) and hαCGRP8–37 (100 nmol/kg; intravenously), but not MAb C4.19 IgG (up to 3 mg/rat; intravenously) or normal mouse Fab′ fragment (2 mg/rat; intravenously), blocked the increased skin blood flow response to antidromic stimulation of the saphenous nerve. 5. The mean percentage changes in skin blood flow parameters due to MAb C4.19 Fab′ fragment were significantly different from those due to normal mouse Fab′ fragment (unpaired t-test; P < 0.05) but not from those due to hαCGRP8–37. 6. The results demonstrate the pharmacokinetic advantage of Fab′ fragment over IgG for immunoblockade studies in vivo and support the role of CGRP in mediating skin vasodilatation.


Diabetes ◽  
1990 ◽  
Vol 39 (2) ◽  
pp. 260-265 ◽  
Author(s):  
J. M. Molina ◽  
G. J. Cooper ◽  
B. Leighton ◽  
J. M. Olefsky

2000 ◽  
Vol 279 (4) ◽  
pp. H1654-H1660 ◽  
Author(s):  
Yasushi Takahashi ◽  
Maartje De Vroomen ◽  
Christine Roman ◽  
Michael A. Heymann

Fetal pulmonary blood flow is regulated by various vasoactive substances. One, calcitonin gene-related peptide (CGRP), increases pulmonary blood flow. We examined four key physiological mechanisms underlying this response using the blocker drugs CGRP receptor blocker (CGRP8–37), nitric oxide synthase inhibitor [ N ω-nitro-l-arginine (l-NNA)], adenosine triphosphate-dependent potassium (KATP) channel blocker (glibenclamide), and cyclooxygenase inhibitor (indomethacin) in 17 near-term fetal sheep. Catheters were placed in the left (LPA) and main pulmonary arteries, and an ultrasonic flow transducer was placed around the LPA to measure flow continuously. CGRP was injected directly into the LPA (mean 1.02 μg/kg) before and after blockade, and responses to CGRP were statistically compared. Before blockade, CGRP increased LPA blood flow from 23 ± 25 to 145 ± 77 ml/min (means ± SD), and these increases were significantly attenuated by CGRP8–37( n = 6; 91% inhibition), l-NNA ( n = 6; 86% inhibition), and glibenclamide ( n = 6; 69% inhibition). No significant changes were found with indomethacin ( n = 6; 4% inhibition). Thus, in the fetal pulmonary circulation, CGRP increases pulmonary blood flow not only through its specific receptor but also, in part, through nitric oxide release and KATP channel activation.


Diabetes ◽  
1990 ◽  
Vol 39 (2) ◽  
pp. 260-265 ◽  
Author(s):  
J. M. Molina ◽  
G. J. S. Cooper ◽  
B. Leighton ◽  
J. M. Olefsky

Sign in / Sign up

Export Citation Format

Share Document