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Spontaneous variation in blood pressure is defined as 'blood pressure variability' (BPV). Sinoaortic denervation (SAD) is characterized by BPV without sustained hypertension. In the present study, we investigated whether BPV could be related to vascular β-adrenoceptor desensitization in rats. Three days after surgery (SAD and control), aortic rings were placed in an organ chamber and the relaxation stimulated by β-adrenoceptor agonists, isoprenaline, terbutaline, BRL37344 and cyanopindolol was verified. The participation of intracellular nucleotides signaling pathways was also verified using forskolin, sodium nitroprusside and acetylcholine to induce relaxation. The effects of BPV on the increase in endothelial cytosolic Ca(2+) concentration stimulated by the β2-adrenoceptor agonist was examined by confocal microscopy. In addition, the vascular expression of the β2-adrenoceptor was also examined by immunohistochemistry. The results show that isoprenaline and terbutaline-induced relaxation was lower in the aortas of rats with BPV. Relaxation responses to other vasorelaxant compounds were similar in both groups of rats. Histological analysis revealed a lower level of β2-adrenoceptor and confocal microscopy showed minor cytosolic Ca(2+) concentration in endothelial cells stimulated by the β2-adrenoceptor agonist in rats with BPV. In conclusion, BPV leads to desensitization of the β2-adrenoceptor, which could contribute to worse β-adrenoceptor agonist-induced relaxation in isolated aortas., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The purpose from this study was to investigate the consequences of sensory neurocompensation to carotid balloon injury in diabetic rats on angiotensin II-induced contraction and basal blood flow in contralateral carotid. Concentration-response curves for angiotensin II and blood flow were obtained in contralateral carotid from non-treated or capsaicin-treated streptozotocin-induced diabetic rats that underwent carotid balloon injury. Diabetes increased angiotensin II-induced contraction and impaired the blood flow in non-operated rat carotid. In diabetic rats, balloon injury led to neointima formation, which reduced the blood flow in ipsilateral carotid. Carotid balloon injury in diabetic rats reduced angiotensin II-induced contraction and restored the blood flow in contralateral carotid when compared to diabetic non-operated rat carotid. Capsaicin inhibited the effects evoked by carotid balloon injury on diabetic rat contralateral carotid. Endothelium removal, PEG-catalase (hydrogen peroxide scavenger) or l-NPA (neuronal nitric oxide synthase, nNOS, inhibitor) increased angiotensin II-induced contraction in contralateral carotid from diabetic operated rats to the levels observed in diabetic non-operated rat carotid. Our findings suggest that carotid balloon injury in diabetic rats elicits a neurocompensation that attenuates the diabetic hyperreactivity to angiotensin II in contralateral carotid by a sensory nerves-dependent mechanism mediated by hydrogen peroxide derived from endothelial nNOS. This sensory mechanism also restored the blood flow in this vessel, compensating the impaired blood flow in diabetic rat ipsilateral carotid. Thus, our major conclusions are that Diabetes confers a vasoprotective significance to the neurocompensation to carotid balloon injury in preventing further damage at carotid cerebral irrigation after angioplasty in diabetic subjects., (Copyright © 2013 Elsevier B.V. All rights reserved.)

We aimed to investigate whether hyperhomocysteinemia (HHcy) interferes on carotid vascular reactivity, and how morphological and functional aspects are related. With this purpose male Wistar rats received a solution of dl-homocysteine-thiolactone (1g/kg body weight/day) in the drinking water for 4, 15 and 30 days. Lipid profile, carotid artery-morphology and -responsiveness to acetylcholine, phenylephrine and endothelin-1 were analyzed. Similar increase on homocysteine plasmatic levels occurred in rats treated for 4, 15 and 30 days. High levels of serum cholesterol and triglycerides were observed after HHcy 30 days. Vascular reactivity experiments using standard muscle bath procedures showed that HHcy induced a time-dependent reduction on acetylcholine-induced-relaxation at 4, 15 and 30 days. HHcy enhanced the contractile response of endothelium-intact, but not denuded carotid rings to phenylephrine and endothelin-1, despite the treatment time. Morphometric analysis showed that intimal/medial area ratio was enhanced only at 30 days of HHcy, despite its reduced cell density. The major new finding of the present study is that it establishes a time-course relationship for the events involved on vascular effects associated with HHcy. We demonstrated that alterations on vascular responsiveness precede alterations on arterial structure. Based on such findings it is possible to suggest that vascular dysfunction occurs in early stages while alterations on vessel morphology take place in latest stages of HHcy.

Background: The clinical relevance of the G1896A precore mutation in chronic hepatitis B is still poorly understood., Objectives: To assess the frequency of G1896A precore mutation in Brazilian patients with chronic hepatitis B, as well as its relation to the viral genotype, serum HBV-DNA levels and liver damage., Study Design: Fifty chronic hepatitis B patients (29 HBeAg-negative and 21 HBeAg-positive) were studied. HBV-DNA was quantified by the Amplicor HBV Monitor test and precore region and S gene were amplified and submitted to automatic sequencing. The histological activity index (HAI), degrees of hepatic fibrosis and distribution of core antigen (HBcAg) in hepatocytes were determined., Results: Precore mutation occurred in 1/21 (4.8%) HBeAg-positive patients and in 17/29 (58.6%) HBeAg-negative (p < 0.0001). Genotype D was identified in 56.5%, genotype A in 41.3%, and genotype F in 2.2%. The frequency of genotypes D and A, as well as serum levels of ALT and HBV-DNA were similar in patients infected with wild type and with precore mutant. Patients infected with precore mutant presented a higher frequency of moderate/severe HAI (p: 0.03) and moderate/severe fibrosis and cirrhosis (p: 0.03) than those infected with wild type. There was no association between G1896A mutation and cytoplasmic expression of HBcAg., Conclusions: Precore mutation was frequent among Brazilian subjects with chronic hepatitis B and its presence was associated with greater severity of liver disease.