Vasomotor effects of 5-hydroxytryptamine, histamine, angiotensin ii, acetylcholine, noradrenaline, and bradykinin on the cerebral artery of bottlenose dolphin (Tursiops truncatus)

Abstract

From an evolutionary aspect, dolphins share a very close phylogenetic relationship with pigs. Previously, we characterized porcine cerebral artery responsiveness to intrinsic vasoactive substances. Therefore, here, we investigated dolphin (Tursiops truncatus) cerebral artery responsiveness to 5-hydroxytryptamine (5-HT), histamine (His), angiotensin (Ang) II, acetylcholine (ACh), noradrenaline (NA), and bradykinin (BK) to characterize their related receptor subtypes. We also compared dolphin cerebral artery responsiveness with porcine cerebral artery responsiveness. We found that 5-HT and His induced concentration-dependent contraction of the dolphin cerebral artery. Ketanserin (a 5-HT2 antagonist) and methiothepin (a 5-HT1 and 5-HT2 antagonist) shifted the concentration-response curve for 5-HT to the right. Although diphenhydramine (an H1 antagonist) shifted the concentration-response curve for His to the right, cimetidine (an H2 antagonist) had no such effect. Ang II and ACh did not produce any vasomotor actions. NA induced concentration-dependent relaxation. Propranolol (a β antagonist) shifted the concentration-response curve for NA to the right, whereas phentolamine (an α antagonist) had no significant effect. BK induced relaxation followed by contraction in pre-contracted arteries with intact endothelium. HOE140 (a B2 antagonist) shifted the concentration-response curve for BK to the right, whereas des-Arg9-[Leu8 ]-BK (a B1 antagonist) had no significant effect. These results suggest that 5-HT1, 5-HT2, and H1 receptor subtypes are important in arterial contraction and that β and B2 receptor subtypes modify these contractions to relaxations. The responsiveness of the dolphin cerebral artery is very similar to that of porcine cerebral artery, supporting their evolutionary linkage.