N. Berthiaume et al., CHARACTERIZATION OF RECEPTORS FOR KININS AND NEUROKININS IN THE ARTERIAL AND VENOUS MESENTERIC VASCULATURES OF THE GUINEA-PIG, British Journal of Pharmacology, 115(7), 1995, pp. 1319-1325
1 In the present work, we have studied the microvascular reactivity of
the arterial and venous mesenteric beds of the guinea-pig to bradykin
in, neurokinins and other agents. 2 The vasoactive properties of three
selective agonists for neurokinin receptors, namely [Sar(9),Met (O-2)
(11)]SP (NK1), [beta-Ala(8)]NKA(4-10) (NK2) and [MePhe(7)]NKB (NK3), w
ere evaluated on precontracted arterial and venous mesenteric vasculat
ures of the guinea-pig. The NK1-selective agonist, [Sar(9),Met(O-2)(11
)]SP (1 to 1000 pmol), induced an endothelium-dependent and N-omega-ni
tro-L-arginine methyl ester (L-NAME)-sensitive relaxation of the arter
ial vasculature precontracted with methoxamine, whereas the NK2 and NK
3-selective agonists were virtually inactive at high doses (1000 pmol)
. 3 The three selective neurokinin receptor agonists were inactive in
the non-precontracted arterial and venous mesenteric vasculatures as w
ell as in the precontracted venous mesenteric vasculature. 4 Bradykini
n (0.1 to 100 pmol) induced a marked dose- and endothelium-dependent v
asodilatation of the precontracted arterial and venous vasculatures. E
D(50) values were 5.5 pmol on the arterial side and 1.9 pmol on the ve
nous side. In contrast, desArg(9)-bradykinin was inactive at doses up
to 1000 pmol. Furthermore, on the arterial and venous sides, a higher
dose of bradykinin (1000 pmol), induced a biphasic effect, a transient
constriction followed by a marked and sustained vasodilatation. The v
asodilator effects of bradykinin were abolished by Hoe 140 (0.1 mu M)
and CHAPS, markedly reduced by L-NAME and were unaffected by [Leu(8)]d
esArg(9)-bradykinin (0.1 mu M) On both sides of the mesenteric vascula
ture. Hoe 140 also abolished the arterial vasoconstrictions induced by
high doses of bradykinin. 5 Noradrenaline, angiotensin II and endothe
lin-l produced contractions on both sides of the mesenteric circulatio
n, while acetylcholine (arterial side) and sodium nitroprusside (arter
ial and venous sides) caused vasodilatation. 6 Our study supports the
view that NK1 receptors responsible for vasodilatation are present sol
ely in the endothelium of the arterial mesenteric vasculature of the g
uinea-pig. On the other hand, bradykinin (0.1 to 100 pmol) exerts pred
ominantly vasodilator effects on both sides of the mesenteric vasculat
ure via selective activation of B-2 receptors located on the endotheli
um. The same receptor type located on the smooth muscle appears to be
responsible for the arterial and venous constriction with high doses o
f bradykinin.