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Studies on cutaneous vascular permeability in the rat: increases caused by histamine and histamine-like agents
Abstract:
The pharmacology of histamine-induced increases in microvascular permeability has been studied in rat skin. Histamine caused dose-dependent increases in microvascular permeability, assessed as increases in extravascular albumin accumulation. The responses to histamine were inhibited in a dose-dependent manner by pretreatment with mepyramine and were not changed by cimetidine. 2-(2-Aminoethyl)pyridine also increased microvascular permeability whereas impromidine did not. These results suggest that H1-receptors and not H2-receptors are involved in the permeability response to histamine in rat skin. In contrast, dimaprit increased microvascular permeability and responses to dimaprit exceeded the maximum response to histamine. The response to dimaprit proved to be independent of H2 receptors and was consistent with an indirect response due to mast cell degranulation.
Insights
Histamine increases microvascular permeability in rat skin via H1-receptors, not H2-receptors. Mepyramine blocked histamine effects, while dimaprit
Area of Science:
- Pharmacology
- Physiology
- Histamine Receptor Research
Background:
- Histamine is a key mediator of inflammatory responses.
- Microvascular permeability is crucial for immune cell trafficking and fluid balance.
- Understanding histamine's role in vascular permeability is vital for treating inflammatory conditions.
Purpose of the Study:
- To investigate the specific histamine receptors mediating increased microvascular permeability in rat skin.
- To differentiate the roles of H1 and H2 receptors in histamine-induced vascular effects.
- To explore the mechanisms behind histamine's impact on albumin extravasation.
Main Methods:
- Dose-dependent administration of histamine and its analogues in rat skin models.
- Assessment of microvascular permeability by measuring extravascular albumin accumulation.
- Pharmacological blockade of histamine receptors using specific antagonists like mepyramine (H1) and cimetidine (H2).
Main Results:
- Histamine induced dose-dependent increases in microvascular permeability.
- Mepyramine significantly inhibited histamine-induced permeability, while cimetidine had no effect.
- The H1-receptor selective agonist 2-(2-Aminoethyl)pyridine increased permeability, but the H2-selective agonist impromidine did not.
- Dimaprit, a histamine analogue, also increased permeability, exceeding histamine's maximal response and acting independently of H2 receptors, suggesting mast cell degranulation.
Conclusions:
- Histamine-induced increases in microvascular permeability in rat skin are primarily mediated by H1-receptors.
- H2-receptors do not play a significant role in this specific histamine response in rat skin.
- Dimaprit's potent permeability-increasing effect may involve indirect mechanisms, such as mast cell degranulation, rather than direct H2-receptor activation.