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Substance P increases cyclic GMP levels on coronary postcapillary venular endothelial cells
M Ziche1, L Morbidelli, A Parenti
1Department of Pharmacology, University of Florence, Italy.
Life Sciences
|January 1, 1993
Summary
Substance P (SP) activates nitric oxide (NO) production in microvascular endothelial cells, leading to increased cyclic GMP levels. This demonstrates SP
Area of Science:
- Cardiovascular Research
- Endothelial Cell Biology
- Vascular Pharmacology
Background:
- The vasodilating effect of substance P (SP) is known to be endothelium-dependent.
- The precise mechanism by which SP influences microvascular tone requires further elucidation.
Purpose of the Study:
- To investigate whether substance P (SP) activates nitric oxide (NO) production in cultured venular endothelial cells.
- To determine the role of NO in mediating the effects of SP on cyclic GMP levels in endothelial cells.
Main Methods:
- Cultured coronary postcapillary venular endothelial cells (CVEC) from bovine origin were used.
- Nitric oxide (NO) activation was assessed by measuring intracellular cyclic GMP levels.
- The effects of SP and the NO synthase inhibitor L-NMMA were evaluated.
Main Results:
- Exposure of CVEC to 10 nM SP for 5 minutes doubled basal cyclic GMP levels.
- L-NMMA reduced basal cyclic GMP and abolished the SP-induced increase, but did not affect responses to exogenous NO.
- These findings suggest an autocrine response to NO in microvascular endothelium.
Conclusions:
- Substance P (SP) activates the cyclic GMP pathway in microvascular endothelial cells via nitric oxide (NO) production.
- The microvascular endothelium exhibits an autocrine response to NO, increasing cyclic GMP levels.
- SP plays a role in regulating microvascular function through NO-mediated signaling.