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Potentiation of histamine-induced microvascular permeability by prostaglandin E2 in rat mesentery
Abstract:
The effect of prostaglandin E2 and histamine and their interaction on microvascular permeability in the rat mesentery was examined using fluorescent in vivo microscopy. Leak of a fluorescein-albumin conjugate from microvessels was determined 3 min after the topical application of prostaglandin E2 and/or histamine. The size of the leak (micron 2) was quantitated using a grid over the face of the videomonitor. To determine the role of endogenous prostaglandin, some rats were pretreated with 10 mg kg-1 indomethacin intravenously. All studies were performed coded. Dose-response studies performed with either prostaglandin E2 or histamine alone revealed that each agent increased microvascular permeability in a dose-related fashion. On a molar basis, prostaglandin E2 was more potent than histamine in this regard. When a low dose of prostaglandin E2 was administered together with a low or intermediate dose of histamine, the size of the resulting leak was significantly greater than the sum of the size of leak produced by each agent given separately. When rats were pretreated with 10 mg kg-1 indomethacin intravenously to inhibit prostaglandin synthesis, the histamine dose response was shifted to the right. From these experiments, we conclude that: In the rat mesentery, both topical prostaglandin E2 and histamine increase microvascular permeability to macromolecules in a dose-related fashion. Prostaglandin E2 is significantly more potent than histamine in this regard. Both exogenous and endogenous prostaglandin potentiate histamine's effect on microvascular permeability.
Insights
Prostaglandin E2 and histamine increase microvascular permeability in rats. Prostaglandin E2 is more potent, and both potentiate histamine's effects, especially when prostaglandin synthesis is inhibited.
Area of Science:
- Physiology
- Pharmacology
Background:
- Microvascular permeability is crucial for regulating fluid and solute exchange.
- Prostaglandin E2 (PGE2) and histamine are known mediators of inflammation and vascular responses.
Purpose of the Study:
- To investigate the individual and combined effects of prostaglandin E2 and histamine on microvascular permeability in the rat mesentery.
- To determine the relative potency of PGE2 and histamine in increasing microvascular permeability.
- To elucidate the role of endogenous prostaglandins in mediating histamine's effects.
Main Methods:
- Fluorescent in vivo microscopy was used to visualize and quantify microvascular leakage of fluorescein-albumin conjugate in rat mesentery.
- Topical application of varying doses of prostaglandin E2 and/or histamine.
- Indomethacin pretreatment to inhibit endogenous prostaglandin synthesis.
- Quantitative analysis of leak size using a videomonitor grid.
Main Results:
- Both prostaglandin E2 and histamine increased microvascular permeability in a dose-dependent manner.
- Prostaglandin E2 was found to be more potent than histamine on a molar basis.
- Combined application of PGE2 and histamine resulted in synergistic increases in permeability.
- Inhibition of prostaglandin synthesis shifted the histamine dose-response curve to the right, indicating potentiation.
Conclusions:
- Prostaglandin E2 and histamine independently increase microvascular permeability in the rat mesentery.
- Prostaglandin E2 exhibits greater potency than histamine in this effect.
- Both exogenous and endogenous prostaglandins enhance histamine-induced increases in microvascular permeability.