Vasomotor Effects of Acetylcholine, Bradykinin, Noradrenaline, 5-Hydroxytryptamine, Histamine and Angiotensin II on the Mouse Basilar Artery

Abstract

We investigated the responsiveness of the mouse basilar artery to acetylcholine (ACh), bradykinin (BK), noradrenaline (NA), 5-hydroxytryptamine (5-HT), histamine (His) and angiotensin (Ang) II in order to characterize the related receptor subtypes in vitro. ACh and BK induced endothelium-dependent relaxation of precontracted arteries with U-46619 (a thromboxane A₂ analogue). Atropine (a non-selective muscarinic receptor antagonist) and Nω-nitro-L-arginine (a NO synthase inhibitor, L-NNA) shifted the concentration-response curve for ACh to the right, whereas pirenzepine, methoctramine and pFHHSiD (muscarinic M₁, M₂ and M₃ antagonists, respectively) had no significant effect. L-NNA and HOE140 (a B₂ antagonist) shifted the concentration-response curve for BK to the right, whereas des-Arg⁹-[Leu⁸]-BK (a B₁ antagonist) and indomethacin (a cyclooxygenase inhibitor) had no significant effect. NA failed to produce any vasomotor action. His and Ang II induced concentration-dependent contraction. Diphenhydramine (a H₁ antagonist) shifted the concentration-response curve for His to the right, whereas cimetidine (a H₂ antagonist) had no significant effect. Losartan (an AT₁ antagonist) shifted the concentration-response curve for Ang II to the right, whereas PD123319 (an AT₂ antagonist) had no significant effect. These results suggest that the H₁ and AT₁ receptor subtypes might play an important role in arterial contraction, whereas muscarinic receptor subtypes apart from M₁, M₂ and M₃, and B₂ receptors on the endothelium, might modify these contractions to relaxations.