Effect of Moderate Cooling on Adrenergic Neuroeffector Interaction in Canine Cutaneous Veins

Abstract

Experiments were performed to investigate the effect of moderate cooling on adrenergic neuroeffector interaction in canine cutaneous veins. Helical strips of dog’s saphenous vein, untreated or first incubated with ³H-norepinephrine were mounted for superfusion and isometric tension recording; the overflow of endogenous catecholamines or ³H-norepi-nephrine and its metabolites, respectively, were measured in the superfusate. In other experiments the monoamine oxidase activity or the catechol-O-methyltransferase (COMT) activity of the saphenous vein wall was determined. Moderate cooling (from 37 to 24 °C) decreased the evoked release of endogenous norepinephrine during electrical stimulation of the adrenergic nerve endings in the blood vessel wall. Moderate cooling depressed the overflow of ³H-norepinephrine and its metabolites in unstimulated preparations, during electrical stimulation during superfusion with high K⁺ solution and during exposure to tyramine. Moderate cooling reduced the activity of monoamine oxidase significantly more than that of COMT. The relative alterations in overflow of norepinephrine and its metabolites caused by a same degree of cooling in basal conditions and during the different forms of increased overflow of adrenergic transmitter suggest that lowering the temperature inhibits the exocytotic process, but at the same time slows down the diffusion of norepinephrine from the junctional cleft to the extracellular space to the extent that during sympathetic nerve stimulation at 24 °C the effective junctional concentration of the transmitter may be comparable to that obtained at 37 °C. The inhibitory effect of moderate cooling on the extraneuronal metabolism of norepinephrine appears to affect little the effective junctional concentration of the adrenergic transmitter.

Attenuated noradrenergic sensitivity during local cooling in aged human skin

“…Several human in vivo studies indicate that this response is mediated by α 2 ‐AR stimulation (Ekenvall et al 1988; Pergola et al 1993; Cankar et al 2004), and Pergola et al (1993) and Johnson et al (2004) suggest that the sympathetic release of NA (abolished by bretylium administration in both studies) is necessary to induce this response. Both Pergola et al (1993) and Johnson et al (2004) further speculate that this NA‐dependent phase of VC may be mediated by a local cooling‐induced increase in the release of NA during local cooling, arguing against the in vitro conclusions of Vanhoutte (1980), Janssens et al (1981) and Flavahan (1991) that suggest that pre‐synaptic NA release is depressed with local cooling.…”

“…Additionally, local cooling decreases neuronal NA re‐uptake and increases intracellular Ca 2+ mobilization and Ca 2+ sensitivity in vascular smooth muscle cells (Janssens & Vanhoutte, 1978; Vanhoutte, 1980; Chotani et al 2000; Jeyaraj et al 2001; Philipp et al 2002; Chotani et al 2004). Conversely, NA release from sympathetic nerves is reduced with direct local tissue cooling (Vanhoutte, 1980; Janssens et al 1981; Flavahan, 1991), so the enhanced VC capacity that results from local cooling occurs despite a depressed release of NA from sympathetic nerves.…”

Modulation of the concentration of noradrenaline at the neuro‐effector junction in human saphenous vein

“…Electrical stimulation (2 Hz) in presence of cocaine (3 x 10-5 M) e Basal 9.2 ±0.6 8.1 ±0.4 2 Hz 40.6+±7.9 ** 11.4± 1.1** 2 Hz -hydrocortisone 39.8 ± 6.7 11.5 ± 1.0 (3 X 10 5M) 10.0 ± 0.9 31.4±2.5** 33.9 ± 2.3 2.8± 1.0 7.9±2.5 8.3± 3.9 1.2 ± 0.7 3.8 ± 1.3 3.2 ± 1.2 2.6 ±0.9 5.8 ± 1 .2 5.7 ±0.9 0.9 ±0.1 6.4± 1.0 5.6±0.4 5.4± 1.6 6.5 ± 1.8 6.9± 1.6 1.6 ± 0.3 1.7 ± 0.4 2.3 ±0.6 4.7 ±2.0 6.9 ± 2.6* * 8.7 ± 3.5 ment of noradrenaline followed by intraneuronal deamination (Lorenz, Vanhoutte & Shepherd, 1979;Dalemans, Janssens, Verbeuren & Vanhoutte, 1980 (Verbeuren et al, 1977;1978;De Mey & Vanhoutte, 1980); there was no, or only a slight, increase on the NMN fraction ( (Verbeuren et al, 1977;1978;Muldoon, Vanhoutte &Tyce, 1978;De Mey & Vanhoutte, 1980;Janssens et al, 1981;Verbeuren & Vanhoutte, 1982). Probably the human vein has a smaller capacity than the dog vein to store this metabolite (Verbeuren & Vanhoutte, 1982 (Langer & Enero, 1974).…”

“…One possible explanation of this difference is that in the human vein, NMN is more easily further deaminated by MAO. The human vein compares well with the rabbit vein but differs from the dog vein in that VMA is present in small amounts in the basal efflux and increases with electrical stimulation (Verbeuren et al, 1977;1978;Muldoon, Vanhoutte &Tyce, 1978;De Mey & Vanhoutte, 1980;Janssens et al, 1981;Verbeuren & Vanhoutte, 1982). Probably the human vein has a smaller capacity than the dog vein to store this metabolite (Verbeuren & Vanhoutte, 1982).…”

“…The number of preparations in each series is also the number of patients. Data from superfusion experiments were analysed as described previously (Janssens et al, 1981). In short, from unstimulated preparations samples for column chromatography were collected from the 12th until the 18th min.…”