Leptin, a hormone produced by adipose tissue is associated with obesity as well as enhanced sympathetic nervous activity, hence its systemic administration results in elevated blood pressure whereas in vitro the hormone causes relaxation of the isolated aortic ring and this appears to be dependent on the production of endothelium-derived relaxing factor (EDRF-NO) (Vecchione et al. 2002). Since the pressurized technique is more physiological and since venous responses have not been assessed in response to leptin, the present experiments were designed to determine responses of the pressurized mesenteric resistance artery and vein of the dog to the hormone.

Beagle dogs weighing between 12 and 15 kg were anaesthetized with 100 mg kg^-1 I.V. of α chloralose. The abdomen was opened and between occlusive ties, segments of the mesentery were removed and placed in ice-cold physiological salt solution (PSS) of the composition (mmol) 119 NaCl, 25 NaOH, 4.7 KCl, 1.6 CaCl₂, 1.17 MgSO₄.7H₂O, 1.18 KH₂PO₄, 0.026 NaEDTA and 5.5 glucose, following which the animal was killed by exsanguination. Third order mesenteric veins of diameter 900 µm as well as fourth order mesenteric arteries of diameter 400 µm were dissected out. The vessels were mounted between two glass cannulae in an arteriograph and pressurized to 70 mmHg in the case of the artery and to 10 mmHg in the case of the vein (Hainsworth et al. 2003), and were superfused with PSS of pH 7.4 warmed to 37°C and bubbled with 5 % CO₂-95 % O₂ gas mixture in a 100 ml reservoir. The vessels were allowed to equilibrate for 60-90 min, with two challenges of 10^-6 M noradrenaline (NA) after which experiments were carried out.

Relaxation responses to leptin were determined in vessels that were pre-constricted with NA, before and after the administration of L-NAME (10^-4 M), an inhibitor of EDRF-NO. In some of the vessels, responses of pre-constricted, L-NAME-administered vessels were also determined in response to 10^-5 M sodium nitroprusside (SNP), an NO donor. In both vessels, the relaxation to leptin was dose dependent. In the artery (n = 5) at the concentration of 0.1, 1.0, 10.0 and 30.0 ng ml^-1 the relaxation responses were (% ± S.E.M.) 4.3 ± 1.2, 9.6 ± 1.7, 15.5 ± 1.7 and 20.0 ± 1.6, respectively, and for the vein (n = 8) the corresponding values were 5.4 ± 0.7, 12.8 ± 0.5, 20.7 ± 0.9 and 28.3 ± 1.2. Following the administration of L-NAME, the responses of either the artery or the vein were virtually abolished, e.g. at the dose of 30 ng ml^-1 of leptin, percentage relaxation responses were 4.2 ± 0.9 and 3.6 ± 0.5 in artery and vein, respectively. After L-NAME the relaxation response to SNP still occurred and in the artery this was 73.4 ± 6.8 % while in the vein it was 70.8 ± 7.4 %.

These results indicate that in the pressurized mesenteric artery or vein in the dog, leptin induces vascular relaxation which is mediated largely by EDRF-NO while the responses to the NO donor (SNP) were virtually preserved.

O.S. was a recipient of a Wellcome Trust travel award.