Recent epidemiological data suggest that diabetes is a risk factor for pulmonary arterial hypertension. The aim of the present study was to analyze the link between type 1 diabetes and pulmonary arterial dysfunction in rats. Male Sprague-Dawley rats were randomly divided into a control (saline) and a diabetic group (70 mg/kg streptozotocin). After 6 weeks, diabetic animals showed a downregulation of the lung bone morphogenetic protein receptor type 2 (BMPR2), upregulation of 5-HT2A receptors and cyclooxygenase-2 proteins as measured by Western blot analysis and increased contractile responses to 5-HT in isolated intrapulmonary arteries. The hyperresponsiveness to 5-HT was endothelium-independent and unaffected by inhibition of NO synthase but prevented by indomethacin, the selective cyclooxygenase-2 inhibitor NS398, superoxide dismutase and the NADPH oxidase inhibitor apocynin or chronic treatment with insulin. However, diabetic rats at 6 weeks did not develop elevated right ventricular pressure or pulmonary artery muscularization while a longer exposure (4 months) to diabetes induced a modest but significant increase in right ventricular systolic pressure. In conclusion, type 1 diabetes mellitus in rats induces a number of changes in lung protein expression and pulmonary vascular reactivity characteristic of clinical and experimental pulmonary arterial hypertension but insufficient to elevate pulmonary pressure. Our results further strengthen the link between diabetes and pulmonary arterial hypertension
- Received January 17, 2011.
- Revision received April 25, 2011.
- Accepted April 25, 2011.
- The American Society for Pharmacology and Experimental Therapeutics