Mechamsms of NO/cGMP-dependent vasorelaxation

Matthias Sausbier, Rudolf Schubert, Viktor Voigt, Christoph Hirneiss, Alexander Pfeifer, Michael Korth, Thomas Kleppisch, Peter Ruth, Franz Hofmann

Research output: Contribution to journalArticlepeer-review

212 Scopus citations

Abstract

Both cGMP-dependent and -independent mechanisms have been implicated in the regulation of vascular tone by NO. We analyzed acetylcholine (ACh)- and NO-induced relaxation in pressurized small arteries and aortic rings from wild-type (wt) and cGMP kinase I-deficient (cGKI(-/-)) mice. Low concentrations of NO and ACh decreased the spontaneous myogenic tone in wt but not in cGKI(-/-) arteries. However, contractions of cGKI(-/-) arteries and aortic rings were reduced by high concentrations (10 μmol/L) of 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA-NO). Iberiotoxin, a specific blocker of Ca2+-activated K+ (BK(Ca)) channels, only partially prevented the relaxation induced by DEA-NO or ACh in pressurized vessels and aortic rings. DEA-NO increased the activity of BK(Ca) channels only in vascular smooth muscle cells isolated from wt cGKI(+/+) mice. These results suggest that low physiological concentrations of NO decrease vascular tone through activation of cGKI, whereas high concentrations of DEA-NO relax vascular smooth muscle independent of cGKI and BK(Ca). NO-stimulated, cGKI-independent relaxation was antagonized by the inhibition of soluble guanylyl cyclase or cAMP kinase (cAK). DEA-NO increased cGMP to levels that are sufficient to activate cAK. cAMP-dependent relaxation was unperturbed in cGKI(-/-) vessels. In conclusion, low concentrations of NO relax vessels by activation of cGKI, whereas in the absence of cGKI, NO can relax small and large vessels by cGMP-dependent activation of cAK.

Original languageEnglish
Pages (from-to)825-830
Number of pages6
JournalCirculation Research
Volume87
Issue number9
DOIs
StatePublished - 27 Oct 2000

Keywords

  • Arteries
  • CGMP-dependent protein kinase I
  • K channels

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