Cyclic GMP-independent mechanisms of nitric oxide-induced vasodilation

Chetan Goud, Albert Dipiero, Warren E. Lockette, R. Clinton Webb, John R. Charpie

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


1. The aim of the present study was to test in vitro if NO acts through a cyclic GMP-independent mechanism to activate Ca2+-dependent potassium channels (K+(Ca) ), leading to membrane hyperpolarization and vasodilation in rat tail artery. 2. Acetylcholine and sodium nitroprusside stimulated a significant increase in cyclic GMP (190±23 and 180±15 pmol/g, respectively) compared with agonist-free conditions (132±15 and 130±15 pmol/g, respectively); these agonist-mediated increases in cyclic GMP were completely abolished by treatment with the guanylate cyclase inhibitor methylene blue (122±10 and 60±8 pmol/g, respectively). 3. In contrast, relaxation to acetylcholine (10-7 mol/l; 61±3%) and sodium nitroprusside (10-8 mol/l; 97±1%) were significantly, but not completely, attenuated by methylene blue (30±5 and 79±3%, respectively); maximum relaxation to sodium nitroprusside (10-7 mol/l) was unaffected by methylene blue. 4. Depolarization-induced contraction of vessels with KCl inhibited relaxation to both acetylcholine (10-7 mol/l; 18±4%) and sodium nitroprusside (10-8 mol/l; 57±7%). Furthermore, the specific K+(Ca) antagonist charybdotoxin significantly inhibited relaxation to sodium nitroprusside (10-8 mol/l; 52±7%). 5. An additive inhibitory effect on relaxation to sodium nitroprusside (10-8 mol/l) was observed with a combination of methylene blue and KCl (26±6%) or charybdotoxin (34±3%). 6. These data suggest that NO stimulates membrane hyperpolarization via K+(Ca) activation, in addition to guanylate cyclase, to cause relaxation in rat tail artery. Copyright (C) 1998 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)51-55
Number of pages5
JournalGeneral Pharmacology
Issue number1
StatePublished - Jan 1999
Externally publishedYes


  • Acetylcholine
  • Guanylate cyclase
  • Nitroprusside
  • Rat tail artery

ASJC Scopus subject areas

  • Pharmacology


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