Short-term hypercaloric diet induces blunted aortic vasoconstriction and enhanced vasorelaxation via increased nitric oxide synthase 3 activity and expression in Dahl salt-sensitive rats.

AIM: To elucidate the role of the O(2)(-), H(2)O(2) or NO pathways in aortic angiotensin (Ang)II-induced vasoconstriction in Dahl salt-sensitive (SS) rats compared with control SS-13(BN) rats on a normal or hypercaloric diet. METHODS: Aortic function was assessed using wire myography in 16-week-old rats maintained on a normal diet or a 4-week hypercaloric diet. Nitric oxide synthase (NOS) activity and expression was determined by the conversion of radio-labelled arginine to citrulline and Western blot analysis respectively. RESULTS: On normal diet, AngII-induced vasoconstriction was greater in SS than SS-13(BN) rats. Polyethylene glycol superoxide dismutase (PEG-SOD) reduced the aortic AngII response similarly in both strains on normal diet. Catalase blunted, whereas N(ω)-Nitro-L-arginine methyl ester (L-NAME) did not affect the AngII response in SS rats. In SS-13(BN) rats, catalase had no effect and L-NAME enhanced AngII response. On hypercaloric diet, aortic AngII responsiveness was reduced in SS but unaltered in SS-13(BN) rats compared with their normal diet counterparts. PEG-SOD reduced the AngII response in both rats on hypercaloric diet. Catalase treatment did not alter aortic AngII response, while L-NAME increased the response in SS rats on hypercaloric diet. In SS-13(BN) rats on hypercaloric diet, catalase reduced and L-NAME did not alter the AngII response. Furthermore, aortic endothelial-dependent vasorelaxation was increased in SS rats on hypercaloric diet compared with normal diet and aortic NOS3 activity and expression was increased. CONCLUSION: A short-term hypercaloric diet induces a blunted vasoconstrictive and enhanced vasodilatory phenotype in SS rats, but not in SS-13(BN) rats, via reduced H(2)O(2) and increased NOS3 function.

Pathophysiology of hypertension in pre-eclampsia: a lesson in integrative physiology.

Despite being one of the leading causes of maternal death and a major contributor of maternal and perinatal morbidity, the mechanisms responsible for the pathogenesis of pre-eclampsia have yet to be fully elucidated. However, it is evident that this is a complex disorder involving multiple organ systems, and by using integrative approaches, enormous progress has been made towards understanding the pathophysiology of pre-eclampsia. Growing evidence supports the concept that the placenta plays a central role in the pathogenesis of pre-eclampsia and that reduced uteroplacental perfusion, which develops as a result of abnormal cytotrophoblast invasion of spiral arterioles, triggers the cascade of events leading to the maternal disorder. Placental ischaemia leads to release of soluble placental factors, many of which are classified as anti-angiogenic or pro-inflammatory. Once these ischaemic placental factors reach the maternal circulation, they cause widespread activation and dysfunction of the maternal vascular endothelium that results in enhanced formation of endothelin-1 and superoxide, increased vascular sensitivity to angiotensin II and decreased formation of vasodilators such as nitric oxide. This review highlights these links between placental ischaemia, maternal endothelial activation and renal dysfunction in the pathogenesis of hypertension in pre-eclampsia.