Proceedings of The Physiological Society

University College Cork (2004) J Physiol 560P, C12



Myers,David S; Macarlupu,Jose Luis ; Rivera-Chira,Maria C; Moore,Jonathan P; Hainsworth,Roger ; Drinkhill,Mark J;

1. Institute for Cardiovascular Research, University of Leeds, Leeds, West Yorkshire, United Kingdom. 2. Department of Biological Sciences & Physiology, Universidad Peruana Cayetano Heredia, Lima, Peru.

  • Fig. 1. Responses to cumulative doses concentrations of NA (A) and ACh (B)

The effects of hypobaric hypoxia are widespread and complex. In this study we compared the contractile and relaxation properties of mesenteric arteries from dogs living at high altitude (4338 m; PB = 450 mmHg; HA, n = 8) with those from lowland animals (SL; n = 5). Dogs were anaesthetized with α-chloralose (100 mg kg-1i.v.), the abdomens opened and intestinal segments removed and placed in cold physiological saline solution (PSS) at 4°C. Animals were killed by exsanguination following a lethal dose of anaesthetic. Lengths of fourth order mesenteric arteries (approx diameter 400 μm) were dissected free and cannulated in a pressure myograph. They were perfused (at 70 mmHg) and superfused with PSS at 37°C and pH 7.4, which was gassed with CO2 (35 mmHg) in oxygen. Changes in the luminal diameter were determined using a video tracking device. The vessels were allowed to equilibrate for 60-90 min., after which concentration-response curves were determined for noradrenaline (NA). Relaxation responses to acetylcholine (ACh) were determined following preconstriction with NA to 50 % of the resting diameter and expressed as percent of the preconstriction. Tests were done before and after L-NAME (10-4 M), an inhibitor of endothelial nitric oxide synthase activity. SL and HA vessels constricted in response to NA (Fig. 1A). The responses of HA vessels, however, were significantly smaller at doses of 3 x 10-7 to 10-6 M (two way repeated measures ANOVA P < 0.05). ACh before L-NAME, caused relaxation in both groups (Fig. IB). After L-NAME, responses in vessels from SL animals were greatly reduced 100.3 ± 1.6 % to 25.5 ± 12.2 (mean ± s.e.m.; paired t test, P > 0.05 ). In HA vessels, however, the maximal responses were not significantly changed after L-NAME, although the responses were significantly smaller at ACh concentrations up to an including 10-6M. These results demonstrate that mesenteric arteries from highland dogs are much less responsive to NA. Furthermore, the finding that in the highland dogs Lα-NAME does not alter the maximum vasodilatory response to ACh implies that endothelial function is different. It suggests that, in addition to the endothelial nitric oxide NO pathway, vasodilation in highland animals is mediated by other mechanism(s).

Where applicable, experiments conform with Society ethical requirements