Baroreflex sensitivity differs among same strain Wistar rats from the same laboratory

Previous studies showed that a proportion of normotensive Sprague-Dawley rats spontaneously exhibit lower baroreflex sensitivity. However, investigations have not yet been carried out on Wistar rats. We aimed to compare baroreflex sensitivity among rats from the same strain and the same laboratory. Male Wistar normotensive rats (300–400g) were studied. Cannulas were inserted into the abdominal aortic artery through the right femoral artery to measure mean arterial pressure and heart rate. Baroreflex was calculated as the derivative of the variation of heart rate in function of the mean arterial pressure variation (ΔHR/ΔMAP) tested with a depressor dose of sodium nitroprusside (50 µg/kg) and with a pressor dose of phenylephrine (8µg/kg) in the right femoral venous approach through an inserted cannula. We divided the rats into four groups: i) high bradycardic baroreflex, baroreflex gain less than −2 tested with phenylephrine; ii) low bradycardic baroreflex, baroreflex gain between −1 and −2 tested with phenylephrine; iii) high tachycardic baroreflex, baroreflex gain less than −3 tested with sodium nitroprusside; and iv) low tachycardic baroreflex, baroreflex gain between −1 and −3 tested with sodium nitroprusside. Approximately 71% of the rats presented a decrease in bradycardic reflex while around half showed an increase in tachycardic reflex. No significant changes in basal mean arterial pressure and heart rate, tachycardic and bradycardic peak and heart rate range were observed. There was a significant change in baroreflex sensitivity among rats from the same strain and the same laboratory

Nicotinic acetylcholine receptor subunit variants are associated with blood pressure; findings in the Old Order Amish and replication in the Framingham Heart Study

<p>Abstract</p> <p>Background</p> <p>Systemic blood pressure, influenced by both genetic and environmental factors, is regulated via sympathetic nerve activity. We assessed the role of genetic variation in three subunits of the neuromuscular nicotinic acetylcholine receptor positioned on chromosome 2q, a region showing replicated evidence of linkage to blood pressure.</p> <p>Methods</p> <p>We sequenced <it>CHRNA1</it>, <it>CHRND </it>and <it>CHRNG </it>in 24 Amish subjects from the Amish Family Diabetes Study (AFDS) and identified 20 variants. We then performed association analysis of non-redundant variants (n = 12) in the complete AFDS cohort of 1,189 individuals, and followed by genotyping blood pressure-associated variants (n = 5) in a replication sample of 1,759 individuals from the Framingham Heart Study (FHS).</p> <p>Results</p> <p>The minor allele of a synonymous coding SNP, rs2099489 in <it>CHRNG</it>, was associated with higher systolic blood pressure in both the Amish (p = 0.0009) and FHS populations (p = 0.009) (minor allele frequency = 0.20 in both populations).</p> <p>Conclusion</p> <p><it>CHRNG </it>is currently thought to be expressed only during fetal development. These findings support the Barker hypothesis, that fetal genotype and intra-uterine environment influence susceptibility to chronic diseases later in life. Additional studies of this variant in other populations, as well as the effect of this variant on acetylcholine receptor expression and function, are needed to further elucidate its potential role in the regulation of blood pressure. This study suggests for the first time in humans, a possible role for genetic variation in the neuromuscular nicotinic acetylcholine receptor, particularly the gamma subunit, in systolic blood pressure regulation.</p

Leukocyte telomere length and mitochondrial DNA copy number associate with endothelial function in aging-related cardiovascular disease

BackgroundWe investigated the association between leukocyte telomere length, mitochondrial DNA copy number, and endothelial function in patients with aging-related cardiovascular disease (CVD).MethodsIn total 430 patients with CVD and healthy persons were enrolled in the current study. Peripheral blood was drawn by routine venipuncture procedure. Plasma and peripheral blood mononuclear cells (PBMCs) were collected. Cell-free genomic DNA (cfDNA) and leukocytic genomic DNA (leuDNA) were extracted from plasma and PBMCs, respectively. Relative telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) were analyzed using quantitative polymerase chain reaction. Endothelial function was evaluated by measuring flow-mediated dilation (FMD). The correlation between TL of cfDNA (cf-TL), mtDNA-CN of cfDNA (cf-mtDNA), TL of leuDNA (leu-TL), mtDNA-CN of leuDNA (leu-mtDNA), age, and FMD were analyzed based on Spearman's rank correlation. The association between cf-TL, cf-mtDNA, leu-TL, leu-mtDNA, age, gender, and FMD were explored using multiple linear regression analysis.Resultscf-TL positively correlated with cf-mtDNA (r = 0.1834, P = 0.0273), and leu-TL positively correlated with leu-mtDNA (r = 0.1244, P = 0.0109). In addition, both leu-TL (r = 0.1489, P = 0.0022) and leu-mtDNA (r = 0.1929, P &lt; 0.0001) positively correlated with FMD. In a multiple linear regression analysis model, both leu-TL (β = 0.229, P = 0.002) and leu-mtDNA (β = 0.198, P = 0.008) were positively associated with FMD. In contrast, age was inversely associated with FMD (β = −0.426, P &lt; 0.0001).ConclusionTL positively correlates mtDNA-CN in both cfDNA and leuDNA. leu-TL and leu-mtDNA can be regarded as novel biomarkers of endothelial dysfunction

Sprouted Innervation into Uterine Transplants Contributes to the Development of Hyperalgesia in a Rat Model of Endometriosis

Endometriosis is an enigmatic painful disorder whose pain symptoms remain difficult to alleviate in large part because the disorder is defined by extrauteral endometrial growths whose contribution to pain is poorly understood. A rat model (ENDO) involves autotransplanting on abdominal arteries uterine segments that grow into vascularized cysts that become innervated with sensory and sympathetic fibers. ENDO rats exhibit vaginal hyperalgesia. We used behavioral, physiological, and immunohistochemical methods to test the hypothesis that cyst innervation contributes to the development of this hyperalgesia after transplant. Rudimentary sensory and sympathetic innervation appeared in the cysts at two weeks, sprouted further and more densely into the cyst wall by four weeks, and matured by six weeks post-transplant. Sensory fibers became abnormally functionally active between two and three weeks post-transplant, remaining active thereafter. Vaginal hyperalgesia became significant between four and five weeks post-transplant, and stabilized after six to eight weeks. Removing cysts before they acquired functional innervation prevented vaginal hyperalgesia from developing, whereas sham cyst removal did not. Thus, abnormally-active innervation of ectopic growths occurs before hyperalgesia develops, supporting the hypothesis. These findings suggest that painful endometriosis can be classified as a mixed inflammatory/neuropathic pain condition, which opens new avenues for pain relief. The findings also have implications beyond endometriosis by suggesting that functionality of any transplanted tissue can be influenced by the innervation it acquires

Consequences of perinatal treatment with l-arginine and antioxidants for the renal transcriptome in spontaneously hypertensive rats

Treating spontaneously hypertensive rats (SHR) with l-arginine, taurine, and vitamins C and E (ATCE) during nephrogenesis (2 weeks before to 4 weeks after birth) persistently lowers blood pressure. Hypothetically, differential gene expression in kidney of SHR vs. normotensive Wistar–Kyoto rats (WKY) is partially corrected by maternal ATCE in SHR. Differential gene expression in 2-days, 2-weeks, and 48-week-old rats was studied using oligonucleotide chips. Transcription factor binding sites (TFBS) of differentially expressed genes were analyzed in silico. Differential gene expression varied between SHR+ATCE and SHR, suggesting both direct and indirect effects; but, few genes were modulated toward WKY level and there was little overlap between ages. TFBS analysis suggests less Elk-1-driven gene transcription in both WKY and SHR+ATCE vs. SHR at 2 days and 2 weeks. Concluding, in SHR, persistent antihypertensive effects of maternal ATCE are not primarily due to persistent corrective transcription. Less Elk-1-driven transcription at 2 days and 2 weeks may be involved

Quantitative structure-activity studies on 2-alkylaminoethoxy-1,4-benzodioxanes with local anesthetic activity

The structure-activity relations of 43 2-alkylaminoethoxy derivs. of 1,4-benzodioxane were evaluated in local anesthetic tests on guinea pigs. Factor and Hansch statistical analyses were used for the detn. of contributions of 2 amino substituents and 1 addnl. alkyl or benzyl substituent

Effects of renal denervation on renal pelvic contractions and connexin expression in rats

Aims: The renal pelvis shows spontaneous rhythmic contractile activity. We assessed to what extent this activity depends on renal innervation and studied the role of connexins in pelvic contractions. Methods: Rats underwent unilateral renal denervation or renal transplantation. Renal pelvic pressure and diuresis were measured in vivo. Spontaneous and agonist-induced contractions of isolated renal pelves were investigated by wire myography. Rat and human renal pelvic connexin mRNA abundances and connexin localization were studied by real-time PCR and immunofluorescence respectively. Results: Renal denervation or transplantation increased renal pelvic pressure in vivo by about 60 and 150%, respectively, but did not significantly affect pelvic contraction frequency. Under in vitro conditions, isolated pelvic preparations from innervated or denervated kidneys showed spontaneous contractions. Pelves from denervated kidneys showed about 50% higher contraction frequencies than pelves from innervated kidneys, whereas contraction force was similar in pelves from denervated and innervated kidneys. There was no denervation-induced supersensitivity to noradrenaline or endothelin-1. Renal denervation did not increase pelvic connexin37, 40, 43 or 45 mRNA abundances. Gap junction blockade had no effect on spontaneous pelvic contractile activity. Conclusions: The denervation-induced effect on pelvic pressure may be the consequence of the enhanced diuresis. The mechanisms underlying the denervation-induced effects on pelvic contraction frequency remain unknown. Our data rule out a major role for two important candidates, by showing that renal denervation neither induced supersensitivity to contractile agonists nor increased connexin mRNA abundance in the pelvic wall