Effects of atrial natriuretic factor on cyclic GMP systhesis in rat vascular smooth muscle cells in culture

Kazuhisa Takeuchi, Keishi Abe, Makito Sato, Minoru Yasujima, K. Omata, Masahiro Tanno, Masahiro Kozuki, Kaoru Yoshinaga

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To elucidate the molecular mechanism of the vascular action of atrial natriuretic factor (ANF), we investigated the effect of synthetic rat ANF (atriopeptin III) on intracellular cyclic guanosine-5': 3'-monophosphate (cGMP) production in vascular smooth muscle cells (VSMC) in culture from rat mesenteric artery, and compared the effect of ANF on cGMP production with that of sodium nitroprusside (SNP). ANF-stimulated cGMP production rapidly within 2 min, and the production was enhanced by phosphodiesterase inhibitor isobutylmethylxanthine (IBMX). Both ANF and SNP increased the level of intracellular cGMP in a dose dependent manner. The effects of ANF and SNP were additive to each other, and methylene blue inhibited the effect of SNP but not that of ANF. ANF-stimulated cGMP production was not affected by the depletion of extracellular calcium ion (Ca2+) or calcium antagonists (verapamil and nifedipine). Preincubation with kallikrein inhibited the stimulatory effect of ANF on cGMP production in a dose dependent manner but not that of SNP. The effect of kallikrein was abolished by serine protease inhibitors, aprotinin and gabexate mesilate (FOY). The cGMP production in response to ANF was greater in renal VSMC than mesenteric VSMC. These results in cultured VSMC suggest the followings: (i) ANF may stimulate cGMP production through the activation of guanylate cyclase, (iii) extracellular Ca2+ does not affect cGMP production by ANF, (iv) the vascular effect of ANF may possibly be regulated by vascular kallikrein lacolly, and if cGMP is involved in the vascular action of ANF, (v) ANF may have specific vasodilatory effect in renal vascular bed.

Original languageEnglish
Pages (from-to)29-39
Number of pages11
JournalJapanese Journal of Nephrology
Issue number1
Publication statusPublished - 1987


  • atrial natriuretic factor
  • cultured vascular smooth muscle cells
  • cyclic guanosine monophosphate
  • kallikrein
  • sodium nitroprusside

ASJC Scopus subject areas

  • Nephrology


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