Response of cultured cerebral artery smooth muscle cells to the nitric oxide vasodilators, nitroglycerin and sodium nitroprusside

Hong Tao, Li Ming Zhang, Manuel R Castresana, Walter H. Newman, Samuel D. Shillcutt

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We characterized the response of soluble guanylyl cyclase in smooth muscle cells cultured from cerebral vessels to the nitric oxide (NO)producing vasodilators, nitroglycerin (NTG) and sodium nitroprusside (SNP) and determined the ability of these agents to induce tolerance. Smooth muscle cells were isolated from porcine basilar, anterior and middle cerebral, and internal carotid arteries. Following an initial series of experiments using NTG at various concentrations and times of exposure to determine conditions, concentration-response curves of intracellular guanosine 3',5'-cyclic monophosphate (cGMP) to NTG and SNP were determined in cells pretreated for 1 h with 100 μmol NTG to induce tolerance and compared with response curves in control cells. Basal cGMP levels were 2.1 ± 0.4 pmol/mg cell protein (n = 16). Both NTG and SNP increased cGMP in nontolerant cells, and SNP was more effective. Maximum concentrations of SNP (1 mmol/L) increased cGMP to 163 ± 5.9 pmol/mg versus 21 ± 2.4 pmol/mg for 1 mmol/L NTG (p < 0.01). Cells made tolerant to NTG were unresponsive to NTG up to 1 mmol/L but remained responsive to SNP. However, the response curve to SNP was significantly depressed by ~25%. Following washout of NTG in tolerant cells, the response of cGMP to SNP returned to control within 12 h, while response to NTG required 36 h. Similar experiments were conducted in cells initially made tolerant to SNP. These results indicate that cerebral artery smooth muscle cells in culture express a functioning soluble guanylyl cyclase and the enzymes that are necessary to metabolize NTG to NO. Prolonged exposure of the cells to NTG induced tolerance as well as cross-tolerance to SNP.

Original languageEnglish (US)
Pages (from-to)58-64
Number of pages7
JournalJournal of Neurosurgical Anesthesiology
Volume9
Issue number1
DOIs
StatePublished - Jan 1 1997

Fingerprint

Cerebral Arteries
Nitroglycerin
Nitroprusside
Vasodilator Agents
Smooth Muscle Myocytes
Nitric Oxide
Cyclic GMP
Internal Carotid Artery
Swine
Cell Culture Techniques

Keywords

  • Cerebral arteries
  • cGMP
  • Cultured smooth muscle cells
  • Nitroglycerin
  • Sodium nitroprusside
  • Soluble guanylyl cyclase

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

Cite this

Response of cultured cerebral artery smooth muscle cells to the nitric oxide vasodilators, nitroglycerin and sodium nitroprusside. / Tao, Hong; Zhang, Li Ming; Castresana, Manuel R; Newman, Walter H.; Shillcutt, Samuel D.

In: Journal of Neurosurgical Anesthesiology, Vol. 9, No. 1, 01.01.1997, p. 58-64.

Research output: Contribution to journalArticle

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