Title Page Impaired Vasoconstriction and Nitric Oxide-Mediated Relaxation in Pulmonary Arteries of Hypoxia-and Monocrotaline-Induced Pulmonary Hypertensive Rats Running Title Page Running Title: Vascular Function in Pulmonary Hypertension

List of Non-standard Abbreviations: Ach acetylcholine EDRF endothelium-derived relaxing factor L-NAME N MCT-treated than normoxic rats. Acetylcholine-induced relaxation was less in pulmonary artery of hypoxic and MCT-treated than normoxic rats, suggesting reduced effects of endothelium-derived vasodilators. The NOS inhibitor L-NAME and guanylate cyclase inhibitor ODQ inhibited acetylcholine relaxation, suggesting that it was mediated by NO-cGMP. The NO donor sodium nitroprusside caused less relaxation in pulmonary artery of hypoxic and MCTtreated than normoxic rats, suggesting decreased responsiveness of vascular smooth muscle cells (VSMCs) to vasodilators. Phenylephrine and KCl contraction, and acetylcholine and sodium nitroprusside relaxation were not different in mesenteric arteries from all groups. In lung tissue sections, the wall thickness of pulmonary arterioles was greater in hypoxic-and MCT-treated than normoxic rats. The specific reductions in pulmonary, but not systemic, arterial vasoconstriction and vasodilation in hypoxia-and MCT-induced PH are consistent with the possibility of de-differentiation of pulmonary VSMCs to a more proliferative/synthetic and less contractile phenotype in PH

Title Page Dissociation of Hyperglycemia from Altered Vascular Contraction and Relaxation Mechanisms in Caveolin-1 Null Mice Running Title Page Running Title: Glycemic and Vascular Dysfunction in Cav-1 Deficiency

cav-1 -/-<WT; endothelium removal, the NOS blocker L-NAME or soluble guanylate cyclase (sGC) inhibitor ODQ enhanced Phe contraction, and metformin blunted this effect. Acetylcholine (ACh)-induced relaxation was in cav-1 -/->WT, abolished by endotheliumremoval, L-NAME or ODQ, and reduced with metformin. NO donor sodium nitroprusside was more potent in inducing relaxation in cav-1 -/-than WT, and metformin reversed this effect. Aortic eNOS, AMPK and sGC were in cav-1 -/->WT, and metformin decreased total and phosphorylated eNOS and AMPK in cav-1 -/-. Thus metformin inhibits both vascular contraction and NO-cGMP-dependent relaxation, but does not affect BP or blood glucose in cav-1 -/-mice, suggesting dissociation of hyperglycemia from altered vascular function in cav-1 deficiency states. JPE