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OtherCARDIOVASCULAR PHARMACOLOGY

Angiotensin Inhibits Neurotransmission of Calcitonin Gene-Related Peptide-Containing Vasodilator Nerves in Mesenteric Artery of Spontaneously Hypertensive Rats

Hiromu Kawasaki, Makoto Takenaga, Hiroaki Araki, Kojirou Futagami and Yutaka Gomita
Journal of Pharmacology and Experimental Therapeutics February 1998, 284 (2) 508-515;
Hiromu Kawasaki
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Makoto Takenaga
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Hiroaki Araki
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Kojirou Futagami
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Yutaka Gomita
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Abstract

The role of angiotensin (Ang) in neurotransmission of calcitonin gene-related peptide (CGRP)-containing vasodilator nerves in perfused mesenteric vascular beds isolated from spontaneously hypertensive rats (SHR) (8- and 15-week-old) and age-matched Wistar Kyoto rats (WKY) was investigated. In both SHR and WKY preparations precontracted by continuous perfusion of Krebs’ solution containing 7 μM methoxamine plus 5 μM guanethidine, periarterial nerve stimulation (PNS; 1 and 2 Hz) produced a frequency-dependent vasodilation, which was abolished by 100 nM tetrodotoxin and 500 nM CGRP(8–37) (CGRP receptor antagonist). The PNS-induced vasodilation in the SHR decreased with age and was smaller than that in the WKY. The neurogenic vasodilation in the SHR but not WKY was significantly inhibited by N-acetyltetradecapeptide renin substrate (RS, 100 and 500 nM), AngI (50 and 100 nM) and AngII (50 and 100 nM). The inhibitory effects of RS, AngI and AngII were abolished by the AngII receptor antagonist, [Sar1,Ile8]AngII (500 nM). The effect of RS and AngI was inhibited by captopril (5 μM) and temocapril (500 nM). AngII (100 nM) had no effect on vasodilator response to exogenously infused CGRP (100 pmol). PNS (2 Hz) of perfused mesenteric vascular beds increased the release of CGRP-like immunoreactivities (CGRP-LI) in the perfusate, which was less in 15-week-old SHR than in age-matched WKY. AngII (100 nM) significantly inhibited the neurogenic release of CGRP-LI in the SHR but not in the WKY. These results suggest that exogenous and locally converted AngII, via AngII receptors, modulates the neurotransmission of CGRP-containing vasodilator nerves by inhibiting CGRP release from the nerve.

Footnotes

  • Send reprint requests to: Hiromu Kawasaki, Ph.D., Department of Clinical Pharmaceutical Science, Faculty of Pharmaceutical Sciences, Okayama University, 1–1-1 Tsushimanaka, Okayama 700, Japan.

  • ↵1 This study was supported in part by Grants-in-Aid 08672611 and 09672326 for Scientific Research from the Ministry of Education, Science and Culture of Japan.

  • Abbreviations:
    ACE
    angiotensin converting enzyme
    Ang
    angiotensin
    CGRP
    calcitonin gene-related peptide
    CGRP-LI
    calcitonin gene-related peptide-like immunoreactivities
    NANC
    nonadrenergic noncholinergic
    PG
    prostaglandin
    PNS
    periarterial nerve stimulation
    RS
    N-acetyltetradecapeptide renin substrate
    SHR
    spontaneously hypertensive rat
    TTX
    tetrodotoxin
    WKY
    Wistar Kyoto rat
    • Received April 29, 1997.
    • Accepted October 22, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 284, Issue 2
1 Feb 1998
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OtherCARDIOVASCULAR PHARMACOLOGY

Angiotensin Inhibits Neurotransmission of Calcitonin Gene-Related Peptide-Containing Vasodilator Nerves in Mesenteric Artery of Spontaneously Hypertensive Rats

Hiromu Kawasaki, Makoto Takenaga, Hiroaki Araki, Kojirou Futagami and Yutaka Gomita
Journal of Pharmacology and Experimental Therapeutics February 1, 1998, 284 (2) 508-515;

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OtherCARDIOVASCULAR PHARMACOLOGY

Angiotensin Inhibits Neurotransmission of Calcitonin Gene-Related Peptide-Containing Vasodilator Nerves in Mesenteric Artery of Spontaneously Hypertensive Rats

Hiromu Kawasaki, Makoto Takenaga, Hiroaki Araki, Kojirou Futagami and Yutaka Gomita
Journal of Pharmacology and Experimental Therapeutics February 1, 1998, 284 (2) 508-515;
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