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Objectives: The effects of chronic fluoxetine treatment were investigated on blood pressure and on vascular reactivity in the isolated rat aorta., Methods and Results: Male Wistar rats were treated with fluoxetine (10 mg/kg/day) for 21 days. Fluoxetine increased systolic blood pressure. Chronic, but not acute, fluoxetine treatment increased the contractile response induced by phenylephrine, serotonin (5-HT) and KCl in endothelium-intact rat aortas. L-NAME and ODQ did not alter the contraction induced by phenylephrine and 5-HT in aortic rings from fluoxetine-treated rats. Tiron, SC-560 and AH6809 reversed the increase in the contractile response to phenylephrine and 5-HT in aortas from fluoxetine-treated rats. Fluoxetine treatment increased superoxide anion generation (O2(-)) and the expression of cyclooxygenase (COX)-1 in the rat aorta. Reduced expression of nNOS, but not eNOS or iNOS was observed in animals treated with fluoxetine. Fluoxetine treatment increased prostaglandin (PG)F2α levels but did not affect thromboxane (TX)B2 levels in the rat aorta. Reduced hydrogen peroxide (H2O2) levels and increased catalase (CAT) activity were observed after treatment., Conclusions: The major new finding of our study is that chronic fluoxetine treatment induces endothelial dysfunction, which alters vascular responsiveness by a mechanism that involves increased oxidative stress and the generation of a COX-derived vasoconstrictor prostanoid (PGF2α). Moreover, our results evidenced a relation between the period of treatment with fluoxetine and the magnitude in the increment of blood pressure. Finally, our findings raise the possibility that fluoxetine treatment increases the risk for vascular injury, a response that could predisposes to cardiovascular diseases., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Adrenomedullin (AM) is a peptide that displays cardiovascular protective activity. We investigated the effects of chronic ethanol consumption on vascular reactivity to AM and the expression of AM system components in the rat aorta. Male Wistar rats were treated with ethanol (20% vol/vol) for 6 weeks. Vascular reactivity experiments were performed in the isolated rat aorta. Metalloproteinase-2 (MMP-2) levels were determined by gelatin zymography. Nitrite and nitrate generation was measured by chemiluminescence. Protein and mRNA levels of pre-pro-AM, calcitonin receptor-like receptor (CRLR) and RAMP1, 2, and 3 (receptor-activity-modifying proteins) were assessed by western blot and quantitative real-time polymerase chain reaction, respectively. Ethanol intake reduced AM-induced relaxation in endothelium-intact rat aortas, whereas calcitonin gene-related peptide-, acetylcholine-, and sodium nitroprusside-induced relaxation were not affected by ethanol intake. N(G)-nitro-l-arginine-methyl-ester (l-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, and tetraethylammonium reduced AM-induced relaxation in aortic rings from both control and ethanol-treated rats. Ethanol consumption did not alter basal levels of nitrate and nitrite, nor did it affect the expression of MMP-2 in the rat aorta. Ethanol consumption increased mRNA levels of pre-pro-AM and RAMP1. Protein levels of AM, CRLR, and RAMP1, 2, and 3 were not affected by ethanol consumption. The major findings of the present study are that ethanol consumption reduces the vascular relaxation induced by AM and changes the mRNA expression of the components of the AM system in the vasculature. This response could be one of the mechanisms by which ethanol predisposes individuals to vascular dysfunction and hypertension., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: To investigate the effects of chronic ethanol consumption on nitric oxide (NO)-mediated relaxation in rat cavernosal smooth muscle (CSM)., Methods: Male wistar rats were divided into 2 groups: control and ethanol. CSM obtained from both groups were mounted in organ chambers for measurement of isometric tension. Contraction of the strips was induced by electrical field stimulation (EFS, 1-32 Hertz) and phenylephrine. We also evaluated the effect of ethanol consumption on the relaxation induced by acetylcholine (0.01-1000 micromol L(-1)), sodium nitroprusside (SNP, 0.01-1000 micromol L(-1)), or EFS (1-32 Hz) in strips precontracted with phenylephrine (10 micromol L(-1)). Blood ethanol, serum testosterone levels, and basal nitrate generation were determined. Immunoexpression of endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) was also accessed., Results: Ethanol intake for 4 weeks significantly increased noradrenergic nerve-mediated contractions of CSM in response to EFS. The endothelium-dependent relaxation induced by acetylcholine decreased after the ethanol treatment. Ethanol consumption decreased serum testosterone levels but did not affect the nitrate levels on rat CSM. The mRNA and protein levels for eNOS and iNOS receptors were increased in CSM from ethanol-treated rats., Conclusions: Ethanol consumption reduces endothelium-dependent relaxation induced by acetylcholine, but does not affect SNP or EFS-induced relaxation, suggesting that ethanol disrupts the endothelial function. Despite the overexpression of eNOS and iNOS in ethanol-treated rats, the impaired relaxation induced by acetylcholine may suggest that chronic ethanol consumption induces endothelial dysfunction.