Long-lasting cyclic guanosine-3',5'-monophosphate accumulation in the medium of cultured smooth muscle cells from atherosclerotic rabbit aortas in response to exogenous or endogenous nitric oxide.

Abstract

Although atherosclerosis causes a marked inhibition of the endothelium-dependent vasorelaxation it also leads to expression of inducible nitric oxide synthase (iNOS), accompanied by an increase in cyclic GMP content, in the arterial wall. The aim of our present study as to evaluate the influence of atherosclerosis on the soluble guanylyl cyclase pathway in viable cultured smooth muscle cells (SMC) from rabbit atherosclerotic rabbit aortas (atherosclerotic SMC) and from control rabbit aortas (control SMC). In response to 100 microM sodium nitroprusside (SNP), the intracellular production of cyclic GMP was similar in both types of cells, reaching a maximum after 5 min of incubation. In the culture medium, SNP evokes an increased cyclic GMP concentration lasting 6 h in control SMC and 24 h in atherosclerotic SMC. Interleukin-1beta (100 IU/mL), which induces iNOS in SMC from both control and atherosclerotic aortas causes accumulation of cyclic GMIP in the extracellular medium between 3 and 6 h for control SMC and between 3 and 24 h with atherosclerotic SMC. These results demonstrate a long-lasting egression of cyclic GMP in the extracellular medium of cultured SMC from rabbit aortas in response to endogenous or exogenous NO. Since this egression of cyclic GMP lasts longer in atherosclerotic than in control SMC, we suggest that atherosclerosis dysregulates the long-term soluble guanylyl cyclase response to NO in SMC.

• Authors: A Rupin, D Behr-Roussel, T J Verbeuren
• Journal: Fundamental & clinical pharmacology (Fundam Clin Pharmacol) 2000 Sep-Oct Vol. 14 Issue 5 Pg. 453-9 ISSN: 0767-3981 [Print] England
• PMID: 11129085 (Publication Type: Journal Article)

Chemical References

• Culture Media
• Interleukin-1
• Nitric Oxide Donors
• Vasodilator Agents
• Nitroprusside
• Nitric Oxide
• Cyclic GMP

Topics

• Animals
• Aorta
• Arteriosclerosis (metabolism, pathology)
• Culture Media
• Cyclic GMP (metabolism)
• Disease Models, Animal
• Interleukin-1 (pharmacology)
• Male
• Muscle, Smooth, Vascular (drug effects, metabolism)
• Nitric Oxide (pharmacology)
• Nitric Oxide Donors (pharmacology)
• Nitroprusside (pharmacology)
• Rabbits
• Vasodilator Agents (pharmacology)