Diverse interactions of calcitonin gene related peptide and nitric oxide in the gastric and cutaneous microcirculation

1995 ◽  
Vol 73 (7) ◽  
pp. 991-994 ◽  
Author(s):  
P. Holzer ◽  
Ch. Wachter ◽  
M. Jocič ◽  
I. Th. Lippe ◽  
A. Heinemann ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Gastric Mucosa ◽  
Calcitonin Gene Related Peptide ◽  
Afferent Nerve ◽  
Nerve Fibres ◽  
Related Peptide ◽  
Neurogenic Vasodilatation ◽  
Cutaneous Microcirculation ◽  
Cgrp Release ◽  
Calcitonin Gene

Calcitonin gene related peptide (CGRP) is the major mediator of afferent nerve mediated vasodilatation in the gastric mucosa and skin of the rat. Since receptors for CGRP occur on both the vascular endothelium and smooth muscle, it is conceivable that the vascular actions of CGRP involve multiple mechanisms. The vasodilator effect of rat CGRP-α in the rat gastric mucosa is indeed inhibited by blockade of nitric oxide (NO) synthesis, as is the gastric mucosal hyperemia in response to gastric acid challenge, which is mediated by CGRP release from afferent nerve fibres. In contrast, the vasodilator response to rat CGRP-α in the rat hind paw and the CGRP-mediated vasodilatation evoked by antidromic stimulation of afferent nerve fibres do not depend on the formation of NO. These data indicate that NO plays regionally different roles in the local vasodilator action of CGRP. NO is a secondary vasorelaxant messenger of CGRP in the gastric, but not in the cutaneous, microcirculation. However, this L-arginine-derived autacoid may have a role in the irritant-induced CGRP release from afferent vasodilator fibres in the skin.Key words: calcitonin gene related peptide, nitric oxide, microcirculation, gastric mucosa, skin, afferent nerve fibres, neurogenic vasodilatation.

Nitric oxide-mediated neurogenic vasodilatation in isolated monkey lingual arteries

1997 ◽  
Vol 272 (4) ◽  
pp. H1582-H1588
Author(s):  
N. Toda ◽  
K. Ayajiki ◽  
M. Uchiyama ◽  
T. Okamura
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Vasoactive Intestinal Polypeptide ◽  
Calcitonin Gene Related Peptide ◽  
No Synthase ◽  
Related Peptide ◽  
Neurogenic Vasodilatation ◽  
Calcitonin Gene ◽  
Alpha Beta ◽  
Intestinal Polypeptide

In isolated monkey lingual arteries denuded of the endothelium and contracted with prostaglandin F2alpha, transmural electrical stimulation produced a contraction that was reduced by prazosin and reversed to a relaxation by additional treatment with alpha,beta-methylene ATP. The relaxation thus induced was abolished by tetrodotoxin and N(G)-nitro-L-arginine (L-NNA), a nitric oxide (NO) synthase inhibitor, and L- but not D-arginine restored the response in the L-NNA-treated arteries. Under treatment with prazosin and alpha,beta-methylene ATP, the arterial strips responded to nicotine with a relaxation that was not influenced by atropine and timolol but was abolished by hexamethonium, oxyhemoglobin, and methylene blue. The nicotine-induced relaxation was abolished by L-NNA but not by N(G)-nitro-D-arginine and was reversed by L-arginine. Relaxations to exogenously applied NO (acidified NaNO2 solution) were not influenced by L-NNA but were abolished by oxyhemoglobin and methylene blue. The response was not affected in the strips made unresponsive to vasoactive intestinal polypeptide and calcitonin gene-related peptide by desensitization. Histochemical study demonstrated the presence of perivascular neurons containing neuronal NO synthase. It is concluded that monkey lingual arteries are innervated by vasoconstrictor nerves liberating norepinephrine and possibly ATP and also by nonadrenergic noncholinergic vasodilator nerves liberating NO as a neurotransmitter to activate soluble guanylate cyclase. Vasoactive intestinal polypeptide and calcitonin gene-related peptide do not appear to be involved in the neurogenic vasodilatation.

Involvement of calcitonin gene-related peptide in control of human fetoplacental vascular tone

2004 ◽  
Vol 286 (1) ◽  
pp. H230-H239 ◽  
Author(s):  
Yuan-Lin Dong ◽  
Sujatha Vegiraju ◽  
Madhu Chauhan ◽  
Pandu R. R. Gangula ◽  
Gary D. V. Hankins ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Human Placenta ◽  
Vascular Tone ◽  
Umbilical Artery ◽  
Force Measurement ◽  
Isometric Force ◽  
Calcitonin Gene Related Peptide ◽  
Immunofluorescent Staining ◽  
Related Peptide ◽  
Calcitonin Gene

Calcitonin gene-related peptide (CGRP), one of the most potent endogenous vasodilators known, has been implicated in vascular adaptations and placental functions during pregnancy. The present study was designed to examine the existence of CGRP-A receptor components, the calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 1 (RAMP1), in the human placenta and the vasoactivity of CGRP in the fetoplacental circulation. Immunofluorescent staining of the human placenta in term labor using polyclonal anti-CRLR and RAMP1 antibodies revealed that labeling specifically concentrated in the vascular endothelium and the underlying smooth muscle cells in the umbilical artery/vein, chorionic artery/vein, and stem villous vessels as well as in the trophoblast layer of the placental villi. In vitro isometric force measurement showed that CGRP dose dependently relaxes the umbilical artery/vein, chorionic artery/vein, and stem villous vessels. Furthermore, CGRP-induced relaxation of placental vessels are inhibited by a CGRP receptor antagonist (CGRP8–37), ATP-sensitive potassium (KATP) channel blocker (glybenclamide), and cAMP-dependent protein kinase A inhibitor (Rp-cAMPS) and partially inhibited by a nitric oxide inhibitor ( Nω-nitro-l-arginine methyl ester). We propose that CGRP may play a role in the control of human fetoplacental vascular tone, and the vascular dilations in response to CGRP may involve activation of KATP channels, cAMP, and a nitric oxide pathway.

scholarly journals Mechanisms of calcitonin gene-related peptide-induced increases of pulmonary blood flow in fetal sheep

2000 ◽  
Vol 279 (4) ◽  
pp. H1654-H1660 ◽  
Author(s):  
Yasushi Takahashi ◽  
Maartje De Vroomen ◽  
Christine Roman ◽  
Michael A. Heymann
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Pulmonary Blood Flow ◽  
Pulmonary Arteries ◽  
Calcitonin Gene Related Peptide ◽  
Fetal Sheep ◽  
Nitric Oxide Synthase Inhibitor ◽  
Flow Transducer ◽  
Related Peptide ◽  
Calcitonin Gene

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.

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