Histamine and H1 -histamine receptors faster venous circulation

Abstract

The study has analysed the action of histamine in the rabbit venous system and evaluated its potential role in contraction during increased venous pressure. We have found that a great variety exists in histamine sensitivity and H(1) -histamine receptor expression in various types of rabbit veins. Veins of the extremities (saphenous vein, femoral vein, axillary vein) and abdomen (common iliac vein, inferior vena cava) responded to histamine by a prominent, concentration-dependent force generation, whereas great thoracic veins (subclavian vein, superior vena cavas, intrathoracic part of inferior vena cava) and a pelvic vein (external iliac vein) exhibited slight sensitivity to exogenous histamine. The lack of reactivity to histamine was not due to increased activity of nitric oxide synthase (NOS) or heme oxygenase-1. H(1) -histamine receptor expression of veins correlated well with the histamine-induced contractions. Voltage-dependent calcium channels mediated mainly the histamine-induced force generation of saphenous vein, whereas it did not act in the inferior vena cava. In contrast, the receptor-operated channels were not involved in this response in either vein. Tyrosine phosphorylation occurred markedly in response to histamine in the saphenous vein, but not in the inferior vena cava. Histamine induced a prominent ρ kinase activation in both vessels. Protein kinase C and mitogen-activated protein kinase (MAPK) were not implicated in the histamine-induced intracellular calcium sensitization. Importantly, transient clamping of the femoral vein in animals caused a short-term constriction, which was inhibited by H(1) -histamine receptor antagonist in vivo. Furthermore, a significantly greater histamine immunopositivity was detected in veins after stretching compared to the resting state. We conclude that histamine receptor density adapts to the actual requirements of the circulation, and histamine liberated by the venous wall during increased venous pressure contributes to the contraction of vessels, providing a force for the venous return.

Fig 1

Histamine-induced contraction in isolated rabbit vessels. Saphenous vein (open circle) (n = 12), femoral vein (full circle) (n = 7), external iliac vein (open square) (n = 9). The histamine-induced increases in tension are normalized for vessel cross-sectional area, and absolute values of the increase in tension are shown. Data represent mean ± S.E.M.

Fig 2

Histamine-induced contraction in isolated rabbit vessels. Abdominal part (open circle) of inferior vena cava (n = 10), common iliac vein (full circle) (n = 5), intrathoracic part (open square) of inferior vena cava (n = 7). The histamine-induced increases in tension are normalized for vessel cross-sectional area, and absolute values of the increase in tension are shown. Data represent mean ± S.E.M.

Fig 3

Histamine-induced contraction in isolated rabbit vessels. Axillary vein (open circle) (n = 5), right superior vena cava (full circle) (n = 7), subclavian vein (open square) (n = 5). The histamine-induced increases in tension are normalized for vessel cross-sectional area, and absolute values of the increase in tension are shown. Data represent mean ± S.E.M.

Fig 4

H1 histamine receptor expression in various rabbit veins. (A) Specific H₁ immunopositive bands at ∼55 kD of a representative immunoblot and corresponding CytC staining. (B) Optical density of H₁ immunopositive bands, normalized to CytC. n ≥ 3 in each group.

Fig 5

Role of voltage-operated (nifedipine treatment) and receptor operated (SKF-96365 treatment) channels in the histamine-induced contraction of rabbit saphenous vein (grid columns; n = both 6) and abdominal part of inferior vena cava (hatched columns; n = both 5). Contractile force is expressed in % of control. ***P < 0.001.

Fig 6

Effects of inhibition of ρ kinase by 50 μM HA-1077 (n = both 5) or 5 μM Y-27632 (n = both 4) on the histamine-induced contraction in rabbit saphenous vein (grid columns) and abdominal part of inferior vena cava (hatched columns). Contractile force is expressed in % of control. ***P < 0.001.

Fig 7

Original record of the action of ρ kinase inhibition (50 μM H-1077) on the histamine-induced force generation in rabbit saphenous vein.

Fig 8

Typical clamping/release studies in anesthetized rabbit under control condition and after administration of 4 mg/kg i.v. pyrilamine.

Fig 9

Histamine immunostaining in stretched and non-stretched veins of rabbit. Histamine was visualized using DAB chromogen (brown). Immunopositive pixels were selected and counted on images using Image Pro Plus 4.5 software. NC: negative control.