The major new finding from this study is that HHcy induced a marked increase in PE-induced contraction in rat corpus cavernosum by a mechanism that involves increased O2(-) generation and it could play a role in the pathogenesis of erectile dysfunction associated with HHcy.

Stress increases AngII potency in rat carotid by a mechanism that involves the increased generation of PGI and H O and the activation of Akt pathway. Such mechanism could play a pathophysiological role in cardiovascular diseases correlated with stress.

No abstract

Emerging data point the crosstalk between dyslipidemia and renin-angiotensin system (RAS). Advanced dyslipidemia is described to induce RAS activation in the vasculature. However, the interplay between early dyslipidemia and the RAS remains unexplored. Knowing that hamsters and humans have a similar lipid profile, we investigated the effects of early and advanced dyslipidemia on angiotensin II-induced contraction. Cumulative concentration-response curves for angiotensin II (1.0pmol/l to 1.0µmol/l) were obtained in the hamster thoracic aorta. We also investigated the modulatory action of NAD(P)H oxidase on angiotensin II-induced contraction using ML171 (Nox-1 inhibitor, 0.5µmol/l) and VAS2870 (Nox-4 inhibitor, 5µmol/l). Early dyslipidemia was detected in hamsters treated with a cholesterol-rich diet for 15 days. Early dyslipidemia decreased the contraction induced by angiotensin II and the concentration of Nox-4-derived hydrogen peroxide. Advanced dyslipidemia, observed in hamsters treated with cholesterol-rich diet for 30 days, restored the contractile response induced by angiotensin II by compensatory mechanism that involves Nox-4-mediated oxidative stress. The hyporresponsiveness to angiotensin II may be an auto-inhibitory regulation of the angiotensinergic function during early dyslipidemia in an attempt to reduce the effects of the upregulation of the vascular RAS during the advanced stages of atherogenesis. The recovery of vascular angiotensin II functionality during the advanced phases of dyslipidemia is the result of the upregulation of redox-pro-inflammatory pathway that might be most likely involved in atherogenesis progression rather than in the recovery of vascular function. Taken together, our findings show the early phase of dyslipidemia may be the most favorable moment for effective atheroprotective therapeutic interventions.

2), suggesting possible loss of the enzyme superoxide dismutase (SOD). The participation of metabolites derived from eNOS, nNOS and iNOS, that modulate negatively PhE-induced contraction appear to be important in this response. In HHcy, these metabolites, derived primary from iNOS, are damaged, possibly by reducing the activity of NOS, the process of decoupling and/or reduced bioavailability of NO by interaction with reactive oxidative species (ROS) to form peroxynitrite. The expression of nitrotyrosine, inidicador the presence of peroxynitrite, was not altered in HHcy rat corpus cavernosum. Plasma levels of nitrate showed reduced levels of NO in HHcy rats, being suggestive of reduced bioavailability. The HHcy did not alter the expression of mRNA for eNOS, iNOS and nNOS in rat corpus cavernosum. The metabolites of the enzyme cyclooxygenase-1 (COX-1) and COX-2 participate negatively modulating the contraction of PhE and HHcy does not seem to change this modulation. In conclusion, intermediate HHcy, by its ability to increase basal levels of O 2-, may affect the vasoactive function, contraction and relaxation of ET-1 peptide, as well as increase the contraction induced by PhE due to decrease of H 2 O 2 and reduced of the metabolites derived from iNOS in rat corpus cavernosum.