Noradrenaline, β‐adrenoceptor mediated vasorelaxation and nitric oxide in large and small pulmonary arteries of the rat

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Abstract
Noradrenaline induces a meagre vasoconstriction in small muscular pulmonary arteries compared to large conduit pulmonary arteries. We have examined whether this may be partially related to differences in the β‐adrenoceptor‐mediated vasorelaxation component and, in particular, β‐adrenoceptor‐mediated NO release. Noradrenaline induced a bell‐shaped concentration‐response in large (1202±27 μm) and small (334±12 μm) pulmonary arteries of the rat. In large arteries tension increased to 95.6±1.8% of 75 mM KCl (KPSS; n=8) at 2 μM, above which tension declined. The response in small arteries was meagre (12±1.5% KPSS, n=9), peaking at 0.2 μM. NG‐monomethyl‐L‐arginine (L‐NMMA; 100 μM) abolished the decline in tension induced by higher concentrations of noradrenaline in large arteries, and increased maximum tension (117±3.5% KPSS, n=5, Pn=6, Pn=5, Pn=9, Pn=4). β‐Adrenoceptor‐mediated relaxation was examined in arteries constricted with prostaglandin F2α (50 μM). In the presence of propranolol isoprenaline caused an unexpected vasoconstriction, which was abolished by phentolamine (10 μM). In the presence of phentolamine, isoprenaline caused a maximum relaxation of 43.3±2.1% (n=6) in large, and 49.0±4.5% (n=6) in small arteries. L‐NMMA substantially reduced relaxation in large arteries (7.4±1.5%, n=6, Pn=5, P1‐antagonist, 5 μM) reduced relaxation to isoprenaline (large: 34.8±4.5%, n=5; small: 35.0±1.9%,n=6), but in combination with L‐NMMA had no additional effect over L‐NMMA alone. ICI 118551 (β2‐antagonist, 0.1 μM) reduced isoprenaline‐induced relaxation more than atenolol (large: 18.0±4.6%, n=6, Pn=6, Pn=9; small: 6.5±3.6%, n=5). Salbutamol‐induced relaxation was reduced substantially by L‐NMMA in large arteries (control: 34.7±6.4%, n=6; +L‐NMMA: 8.3±1.3%, n=5, Pn=6; +L‐NMMA: 23.0±0.7%, n=5, P<0.05). Relaxation to forskolin was also partially antagonized by L‐NMMA. These results suggest that the meagre vasoconstriction to noradrenaline in small pulmonary arteries is partially due to a greater β‐adrenoceptor‐mediated component than in large arteries. β‐Mediated vasorelaxation in large arteries was largely NO‐dependent, whereas in small arteries a significant proportion was NO‐independent. Noradrenaline stimulation was also associated with NO release that was independent of β‐adrenoceptors.

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