Differential vasopressor actions of selected biogenic amines, including trace amines, in the rat isolated perfused mesenteric vascular network

Abstract

Introduction

Regulation of vascular reactivity of the mesenteric vascular bed is not completely known. There is substantial information on contractile response to catecholamines and serotonin of the splanchnic vascular bed, but little information exists on how trace amines influence vascular tone (1). The purpose of the present investigation was to compare vasoconstrictor responses of selected classic [noradrenaline (NA), methoxamine (M), serotonin (S)] and trace amines [meta-synephrine (SE, phenylephrine), tryptamine (TRP), tyramine (TYR) and beta-phenylethylamine (B-PEA)] in the rat mesenteric circulation. We tested the hypothesis that potency of trace amines will be moderate compared to the other monoamines.

Method

Thirty-six male Sprague-Dawley rats (280–340 g body weight) were killed by concussion and cervical dislocation. The superior mesenteric artery was cannulated and the mesenteric arterial bed excised and placed in a perfusion chamber (2). The bed was perfused at a constant flow rate (4 mL min^-1) with Krebs’ bicarbonate solution, warmed to 37°C and gassed (5% CO₂ in O₂), final pH 7.4. Perfusion pressure was monitored by means of a pressure transducer (Elcomatic EM 750) connected to a computer data acquisition system (AD Instruments Powerlab Chart 5).

Dose-response curves were constructed for NA, M, S, SE, TRP, TYR and B-PEA by bolus doses (range of 0.01–1000 nmoles) of agonists injected in a 100 μL volume. ED₅₀ (the dose required to produce half of the maximum effect, E_Max) and E_Max values were calculated and results expressed as mean ± SEM, n represents the number of animals used.

Results

Sensitivity (ED₅₀) of monoamines followed the order: S (2.9 ± 0.6, n = 6) > NA (16.1 ± 4.3, n = 6) = SE (20.2 ± 4.6, n = 6) > TRP (35.2 ± 6.3, n = 6) = M (53.2 ± 12.2, n = 5). The efficacy (E_Max) sequence was of the rank order: NA (162 ± 20) = SE (139 ± 5) = M (125 ± 22) > S (51 ± 6) = TRP (38 ± 3). Both, Tyr (n = 4) and B-PEA (n = 3) yielded no vasoconstrictor effects on rat mesenteric vascular bed; however, we have recently shown that both of these molecules generate vasodepressor responses in this arterial network (3).

Discussion

Compounds producing dose-related contractions of the mesenteric vascular tree increase vascular resistance and hence may regulate arterial blood pressure. Nevertheless, additional work is warranted to delineate the effects produced at the recently cloned trace amine associated receptors (TAARs) from those, if any, of the classic amine receptors in the mesenteric circulation. Also, to determine their mechanism of action, and to further define the physiological and physiopathological (hypertension and diabetes) roles of TAARs. The outcome of which may open new avenues for therapeutic interventions.

Acknowledgements

M.A.A. was a recipient of a Wellcome Trust Fellowship.

References

Grandy, D.K. (2007). Pharmacol. Ther., 116, 355–390.

McGregor, D.D. (1965). J. Physiol.,177, 21–30.

Broadley, K.J. et al. (2008). Br. J. Nutr., Nov 19, e1–8.