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Nitric oxide relaxes rat tail artery smooth muscle by cyclic GMP-independent decrease in calcium sensitivity of
A Soloviev1, V Lehen'kyi, S Zelensky
1Department of Experimental Therapeutics, Institute of Pharmacology and Toxicology, Academy of Medical Sciences, 14 Ezhena Pot'e, 03057 Kiev, Ukraine. s.a.pharm@naverex.kiev.ua
Cell Calcium
|June 15, 2004
Summary
Nitric oxide (NO) and sodium nitroprusside (SNP) relax rat tail artery smooth muscle via a cyclic guanosine monophosphate (cGMP)-independent pathway, directly reducing myofilament sensitivity to calcium. Glyceryl trinitrate (GTN) relaxation is inhibited by sGC inhibitors.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Smooth Muscle Biology
Background:
- Nitric oxide (NO) is a key signaling molecule in vascular smooth muscle relaxation.
- The cyclic guanosine monophosphate (cGMP) pathway is traditionally considered the primary mechanism for NO-mediated vasodilation.
- Alternative pathways for NO signaling in vascular tone regulation require further investigation.
Purpose of the Study:
- To investigate the mechanisms of nitric oxide (NO) and NO-donor-induced relaxation in rat tail artery smooth muscle.
- To determine the role of the cyclic guanosine monophosphate (cGMP) pathway in NO-mediated relaxation.
- To explore potential cGMP-independent mechanisms of NO action on vascular contractility and calcium sensitivity.
Main Methods:
- Isolated rat tail artery rings were pre-contracted with high potassium chloride (KCl).
- Contractile force and intracellular calcium levels ([Ca2+]i) were measured simultaneously.
- Vascular rings were chemically permeabilized (alpha-toxin, beta-escin, Triton X-100) to assess myofilament calcium sensitivity.
Main Results:
- Authentic NO and sodium nitroprusside (SNP) decreased intracellular calcium and tension, with distinct time courses.
- SNP-induced relaxation was partially attenuated by ODQ but not LY83583, suggesting a complex role for soluble guanylyl cyclase (sGC).
- Glyceryl trinitrate (GTN)-induced relaxation was abolished by both sGC inhibitors, indicating a strictly cGMP-dependent mechanism for GTN.
Conclusions:
- Authentic NO and SNP can relax rat tail artery smooth muscle via a cGMP-independent pathway, likely by reducing myofilament calcium sensitivity.
- The cGMP-dependent pathway is not the sole mechanism for NO-induced relaxation in vascular smooth muscle.
- NO may directly modulate vascular tone by activating protein phosphatases, independent of cGMP.