Pharmacological Actions of Histamine

PHARMACOLOGICAL ACTIONS - HISTAMINE

1.   Blood Vessels

Histamine causes marked dilatation of smaller blood vessels, including arterioles, capillaries and venules. On s.c. injection flushing, especially in the blush area, heat, increased heart rate and cardiac output, with little or no fall in BP are produced. Rapid i.v. injection causes fall in BP which has an early short lasting H₁ and a slow but more persistent H₂ component. With low doses only the H₁ component is manifest since H₁ receptors have higher affinity. Fall in BP due to large doses is completely blocked only by a combination of H₁ and H₂ antagonists. Dilatation of cranial vessels causes pulsatile headache.

Like ACh and many other autacoids, vasodilatation caused by histamine is partly (H₁ component) indirect, mediated through ‘endothelium dependent relaxing factor’ (EDRF): the receptor being located on the endothelial cells. H₂ receptors mediating vasodilatation are located directly on the vascular smooth muscle.

Larger arteries and veins are constricted by histamine: mediated by H₁ receptor on vascular smooth muscle. Histamine also causes increased capillary permeability due to separation of endothelial cells → exudation of plasma. This is primarily a H₁ response.

Injected intradermally, it elicits the triple response consisting of:

Red spot: due to intense capillary dilatation.

Wheal:   due to exudation of fluid from capillaries and venules.

Flare:  i.e. redness in the surrounding area due to arteriolar dilatation mediated by axon reflex.

2.   Heart

Direct effects of histamine on in situ heart are not prominent, but the isolated heart, especially of guinea pig, is stimulated—rate as well as force of contraction is increased. These are primarily H₂ responses but a H₁ mediated negative dromotropic (slowing of AV conduction) effect has also been demonstrated.

3. Visceral smooth muscle

Histamine causes broncho-constriction; guinea pigs and patients of asthma are highly sensitive. Large doses cause abdominal cramps and colic by increasing intestinal contractions. Guineapig uterus is contracted while that or rat is relaxed; human uterus is not much affected as are most other visceral smooth muscles.

Smooth muscle contraction is a H₁ response. In few instances H₂ mediated relaxation is also seen, e.g. bronchial muscle of sheep, human bronchi after H₁ blockade.

4. Glands

Histamine causes marked increase in gastric secretion—primarily of acid but also of pepsin. This is a direct action exerted on parietal cells through H₂ receptors and is mediated by increased cAMP generation, which in turn activates the membrane proton pump (H+ K+ ATPase).

Histamine can increase other secretions also, but the effect is hardly discernable.

5. Sensory Nerve Endings

Itching occurs when histamine is injected i.v. or intracutaneously. Higher concentrations injected more deeply cause pain. These are reflections of the capacity of histamine to stimulate nerve endings.

6. Autonomic Ganglia And Adrenal Medulla

These are stimulated and release of Adr occurs, which can cause a secondary rise in BP.

7. CNS

Histamine does not penetrate bloodbrain barrier—no central effects are seen on i.v. injection. However, intracerebroventricular administration produces rise in BP, cardiac stimulation, behavioural arousal, hypothermia, vomiting and ADH release. These effects are mediated through both H₁ and H₂ receptors.