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Substance P increases microvascular permeability via nitric oxide-mediated convective pathways
L S Nguyen1, A C Villablanca, J C Rutledge
1Division of Cardiovascular Medicine, Wadsworth Veterans Affairs Hospital, Los Angeles, California, USA.
The American Journal of Physiology
|April 1, 1995
Summary
Substance P significantly increases microvascular permeability by enhancing nitric oxide production. This effect is mediated through substance P receptors and blocked by specific antagonists, revealing pathways for albumin flux.
Area of Science:
- Physiology
- Pharmacology
- Vascular Biology
Background:
- Microvascular permeability is crucial for regulating fluid and solute exchange.
- Substance P, a tachykinin neuropeptide, is implicated in inflammatory and vascular responses.
- Understanding the molecular mechanisms of substance P's action on microvessels is essential.
Purpose of the Study:
- To investigate the impact of substance P on microvascular permeability.
- To elucidate the signaling pathways involved in substance P-induced permeability changes.
- To determine the role of nitric oxide in mediating substance P's effects.
Main Methods:
- Perfused isolated frog mesenteric venular capillaries.
- Quantified albumin apparent permeability coefficients (PsAlb) using quantitative fluorescence microscopy.
- Utilized substance P receptor antagonist (CP-96,345) and nitric oxide synthase inhibitor (L-NAME).
Main Results:
- Substance P (10(-11) M) significantly increased PsAlb from 6.8 to 22.3 cm.s-1.10(7).
- The increase in permeability was blocked by CP-96,345 and L-NAME.
- Albumin flux was coupled to transvascular water flow, increasing with microvessel pressure post-substance P treatment.
Conclusions:
- Substance P enhances microvessel permeability via a receptor-mediated mechanism.
- Increased nitric oxide production is a key component of substance P's effect.
- Water-filled convective pathways, likely between endothelial cells, are formed, facilitating albumin transport.