Evidence for direct vasoconstrictor activity of melatonin in ?pressurized? segments of isolated caudal artery from juvenile rats

Abstract

Responses of isolated, 60 mmHg 'pressurized' segments of the distal caudal artery of adult and juvenile Wistar rats to melatonin and the selective alpha 2-adrenoceptor agonist 5-bromo-6-[2-imidazolin-2-ylamino]-quinoxaline bitartrate (UK-14304) were examined using the Halpern pressure myograph. Melatonin showed no direct vasoconstrictor activity in vessels from adult rats, whereas UK-14304 produced moderate vasoconstriction (pD2-7.43 +/- 0.09). In the presence of phenylephrine-induced tone, melatonin produced a variable but small constrictor response (less than 10 microns reduction in diameter) in some vessels; the response to 1 mumol/l UK-14304 was less than in the absence of tone. In vessels isolated from juvenile rats, melatonin caused concentration-dependent vasoconstriction with a maximum response about 70% of the maximum response elicited by UK-14304. Vessels from juvenile rats were more sensitive to melatonin (pD2-9.40 +/- 0.07) than they were to UK-14304 (pD2-8.12 +/- 0.14). In the presence of phenylephrine-induced tone, the vasoconstrictor responses to both melatonin and IK-14304 were markedly less; the sensitivity to melatonin was not different from that seen in the absence of tone. These findings indicate that 'pressurized' segments of the isolated distal caudal artery may provide a simple and convenient, functional model of melatonin receptors. The findings also appear to implicate melatonin in thermoregulatory processes in juvenile rats.

Studies on the vasoconstrictor action of melatonin and putative melatonin receptor ligands in the tail artery of juvenile Wistar rats

“…The localization of these binding sites is discrete (there is no evidence for similar binding sites on either coronary artery, carotid artery or aorta of the rat) and this has been taken as evidence for a thermoregulatory role of the pineal hormone (Viswanathan et al, 1990;Saarela & Reiter, 1993). In support of this proposal, near physiological levels of melatonin (0.3 nM to 1 nM) have been reported to increase vascular tone in both isolated cerebral vessels (Geary et al, 1995;Mahle et al, 1995), the cerebral vascular bed (Capsoni et al, 1995) and the isolated tail artery (Evans et al, 1992). However, the precise nature of the vasoconstriction appears to be a function of the recording technique employed.…”

“…In the case of the tail artery maintained under isometric tension, melatonin is devoid of direct vasoconstriction, but is able to potentiate contractions involving exogenous and endogenous (electrical ®eld stimulation of noradrenaline release) activation of alpha-adrenoceptors (Viswanathan et al, 1990;Krause et al, 1995). In marked contrast, direct vasoconstriction to melatonin has been reported in both the tail (Evans et al, 1992) and cerebral arteries (Geary et al, 1995;Mahle et al, 1995) of the rat when vessels are pressurized and vascular tone measured as changes in lumen diameter. At present the basis of the difference between the two techniques is not known, but both appear to oer a relatively simple method for studying the vascular action of melatonin and characterizing the receptor involved.…”

International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors

“…Activation of MT 1 and MT 2 receptors mediates vasoconstriction and vasodilation, respectively. In the rat caudal artery, which is important for thermoregulation, melatonin causes vasoconstriction, directly contracting pressurized arterial segments (Evans et al, 1992) and potentiating contraction induced by adrenergic nerve stimulation or norepinephrine (Krause et al, 1995;Geary et al, 1998). Various melatonin receptor analogs act as full or partial agonists in the rat caudal artery model, the enantiomers of the melatonin agonist N-acetyl-4-aminomethyl-6-methoxy-9-methyl-1,2,3,4-tetrahydrocarbazole showing a difference (400-fold) in vasoconstrictor potency matching the known difference in melatonin receptor affinity of the two enantiomers (Krause et al, 1995;Ting et al, 1997) Vasoconstriction seems to be mediated by MT 1 receptors because it is not blocked by the MT 2 selective antagonist 4P-PDOT (Doolen et al, 1998;Masana et al, 2002).…”

MT2 Receptors Mediate the Inhibitory Effects of Melatonin on Nitric Oxide-Induced Relaxation of Porcine Isolated Coronary Arteries

“…Three distinct melatonin receptor subtypes, termed MT 1 , MT 2 , and MT 3 receptors, have been identified and shown to mediate the physiological effects of melatonin (Nosjean et al, 2000;Dubocovich et al, 2003). The effects of melatonin on vascular function are complex inasmuch as melatonin receptor activation causes vasoconstriction in certain arteries (Evans et al, 1992;Geary et al, 1997;Ting et al, 1997;Viswanathan et al, 1997) and vasodilation in others (Satake et al, 1991;Weekley, 1991;Doolen et al, 1998). Furthermore, melatonin receptors are not expressed in all blood vessels (Mahle et al, 1997), thus limiting the actions of the hormone to specific regions of the circulation.…”