The role of guanylyl cyclases in the permeability response to inflammatory mediators in pial venular capillaries in the rat

Mosharraf Sarker, P. A. Fraser

    Research output: Contribution to journalArticle

    27 Citations (Scopus)

    Abstract

    Inflammatory mediators have a role in the formation of cerebral oedema and there is evidence that cGMP is an important signal in vascular permeability increase. We have investigated the role and the source of cGMP in mediating the permeability response to acutely applied bradykinin and the histamine H2 agonist dimaprit on single cerebral venular capillaries, by using the single vessel occlusion technique. We found that 8-bromo-cGMP applied acutely resulted in a small and reversible permeability increase with a log EC50 -7.2 ± 0.15 M. KT 5823, the inhibitor of cGMP-dependent protein kinase, abolished the permeability responses to both bradykinin and dimaprit, while zaprinast, an inhibitor of type 5 phosphodiesterase, potentiated the response to bradykinin. On the other hand, L-NMMA blocked the response to dimaprit, but not that to bradykinin. Inhibitors of soluble guanylyl cyclase, LY 85353 and methylene blue, also inhibited the permeability response to dimaprit, but not bradykinin. The permeability responses to thenatriuretic peptides ANP and CNP were of similar magnitude to that of bradykinin with log EC50 -10.0 ± 0.33 M and -8.7 ± 0.23 M, respectively. The natriuretic peptide receptor antagonist HS-142-1 blocked permeability responses to bradykinin as well as to ANP, and leukotriene D4 blocked the responses to CNP and bradykinin, but not to dimaprit. In conclusion, the histamine H2 receptor appears to signal via cGMP that is generated by a NO and soluble guanylyl cyclase, while bradykinin B2 receptor also signals via cGMP but through particulate guanylyl cyclase.

    Original languageEnglish
    Pages (from-to)209-218
    Number of pages10
    JournalJournal of Physiology
    Volume540
    Issue number1
    DOIs
    Publication statusPublished - 1 Apr 2002

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