Poor control of blood glucose in diabetes causes systemic hypertension, which contributes to the development of organ damage. The underlying cause is peripheral vasoconstriction¹ mediated by endothelial dysfunction² and enhanced smooth muscle contractility³. Studies on humans⁴ and rat lungs⁵ suggest that diabetes also affects the pulmonary circulation. We have investigated the reactivity of isolated, intrapulmonary arteries (IPA) to vasoactive agents in a rat model of diabetes. Diabetes was induced in male Wistar rats by i.p.injection of streptozotocin (STZ; 60 mg/kg), with age-matched controls receiving equivalent vehicle. Animals were sacrificed at 3-4 months, after measuring body weight and blood glucose, and conduit and resistance (<250μm i.d.) IPA isolated for wire myography. Experiments were performed at 37^οC in solution containing (mM): NaCl 120, KCl 5, KH₂PO₄ 0.5, Na₂HPO₄ 0.5, CaCl₂ 1.8, MgCl₂ 1, HEPES 10; pH 7.3. Procedures accorded with current UK legislation. Data are expressed as mean ± s.e.m. of n animals and compared using Student’s t-test. At sacrifice, STZ-treated rats weighed 270±7g with blood glucose 250±26 mg/dl (n=17), values significantly (P<0.001) different from controls (360±15g, n=13; 68±4mg/dl glucose). All vessels displayed concentration-dependent constriction to raised extracellular K⁺. In small vessels, the response was maximum at 50mM K⁺ and decreased at higher concentrations, whereas in conduit vessels contraction increased in amplitude up to 110mM. Concentration-effect curves for K⁺ were, however, similar in control and STZ vessels. Phenylephrine (PE) and serotonin (5HT) constricted conduit vessels with pEC₅₀ values of 8.1±0.2 and 6.1±0.3, respectively, and maximum responses 72±18% (n=5) and 81±13% (n=4) of the response to 50mM K⁺. In small vessels, the 5HT concentration-response relationship was similar, but PE had its maximum effect at 100nM, becoming ineffective at higher concentrations. PGF_2α constricted small IPA with pEC₅₀=5.6±0.1 and maximum response 78±13% (n=4) of the K⁺ contraction, but in conduit vessels the response failed to reach maximum at 10µM, where it was nevertheless 100±22% of the K⁺ response. STZ treatment did not significantly alter the concentration-effect curves of any agonist. In contrast, STZ treatment inhibited endothelium-dependent relaxation to carbachol. This was most apparent in conduit vessels, where the maximum relaxation was reduced from 106±12% (n=4) in controls to 44±12% (n=3) in STZ-treated vessels (P<0.05). The results imply that, like systemic vessels, diabetes causes dysfunction of the pulmonary artery endothelium, but the reactivity to a range of vasoconstrictors is preserved.