Effect of Angiotensin receptor blockade on Plasma Osmolality and Neurohumoral Responses to High Environmental Temperature in Rats Fed a High Salt Diet.

Plasma osmolality (pOsmol) and neurohumoral signals play important roles in the pathophysiology of cardiovascular diseases. Our study investigated the effect of high environmental temperature (HET) on neurohumoral responses and pOsmol in rats fed a high salt diet (HSD), with and without angiotensin II receptor blockade (ARB), using telmisartan.  Fifty-six male 8-week old Sprague-Dawley rats (95-110g) were randomly assigned into seven groups of 8 rats. These included control rats (I) fed with 0.3% NaCl diet (normal diet, ND); salt-loaded rats (II) fed with 8% NaCl (high salt) diet; ND rats (III) exposed to HET (38.5±0.5oC ) 4 hours daily per week; rats (IV) fed with 8% NaCl diet and exposed to HET daily. Others included rats (V) fed with 8% NaCl diet and treated with telmisartan (30mg/kg); ND rats (VI) exposed to HET and treated with telmisartan; rats (VI) fed with 8% NaCl diet, exposed to HET and treated with telmisartan. Plasma angiotensin II, aldosterone, vasopressin and norepinephrine (NE) concentrations were determined by ELISA technique; pOsmol from plasma K+, Na+ and Urea. HSD combined with HET in rats synergistically increased pOsmol (P<0.001) with an associated non-synergistic rise in fluid intake (P<0.001), fluid balance (P<0.001), plasma angiotensin II (P<0.01) and aldosterone (P<0.05), NE (P<0.001) and vasopressin (P<0.05) concentrations compared to control. Telmisartan did not alter pOsmol in all the treated-rats, but normalized fluid intake levels and plasma vasopressin in the rats exposed to either HSD or HEt alone. Prolonged exposure of rats to hot environment exacerbated the effect of excess dietary salt on pOsmol, with no effect on angiotensin II-mediated neurohumoral responses.

Sex differences in cardiac and renal responses to a high salt diet in Sprague-Dawley rats.

High dietary salt intake is an important risk factor for cardiovascular and renal diseases. However, sexual disparity exists in the response of target organs to high salt diet (HSD). To determine how sex affects cardiac and renal functions' response to HSD, 20 weanling Sprague-Dawley rats (10 males and 10 females) were divided into 4 groups of 5 rats each. The rats were fed a normal diet (0.3% NaCl) or HSD (8% NaCl) for 12 weeks. Fluid balance (FB) was determined from 24 hrs water intake and voided urine. Blood pressure (BP) was measured via arterial cannulation under anesthesia (25% w/v urethane and 1% w/v α-chloralose; 5 ml/kg, i.p). Serum levels of troponin I, aminotransaminases, creatinine, urea, uric acid and electrolytes as well as urinary concentration of albumin, creatinine, and electrolytes were measured using appropriate assay kits. Values are presented as mean ± S.E.M, compared by two-way ANOVA and Bonferroni post Hoc test. In the male rat, HSD significantly increased BP, serum: Troponin I, LDH and sodium (p < 0.05), urinary: albumin, sodium, potassium and FB (p < 0.05). In the female rat, HSD increased BP, serum: troponin I, LDH, sodium and creatinine clearance (p < 0.05), urinary: albumin, sodium and potassium (p < 0.01). However, HSD increased more, the BP, serum: Troponin I, LDH, urinary albumin and FB in male rats, while HSD increased urinary sodium more in female rats. Basal values in male vs. female of serum LDH and urinary albumin were significantly different. Thus, sex plays an important role in the response of the heart and kidney to salt stress.

Contrasting Views on the Role of Mesenchymal Stromal/Stem Cells in Tumour Growth: A Systematic Review of Experimental Design.

The effect of mesenchymal stromal/stem cells (MSCs) on tumour growth remains controversial. Experimental evidence supports both an inhibitory and a stimulatory effect. We have assessed factors responsible for the contrasting effects of MSCs on tumour growth by doing a meta-analysis of existing literature between 2000 and May 2017. We assessed 183 original research articles comprising 338 experiments. We considered (a) in vivo and in vitro experiments, (b) whether in vivo studies were syngeneic or xenogeneic, and (c) if animals were immune competent or deficient. Furthermore, the sources and types of cancer cells and MSCs were considered together with modes of cancer induction and MSC administration. 56% of all 338 experiments reported that MSCs promote tumour growth. 78% and 79% of all experiments sourced human MSCs and cancer cells, respectively. MSCs were used in their naïve and engineered form in 86% and 14% of experiments, respectively, the latter to produce factors that could alter either their activity or that of the tumour. 53% of all experiments were conducted in vitro with 60% exposing cancer cells to MSCs via coculture. Of all in vivo experiments, 79% were xenogeneic and 63% were conducted in immune-competent animals. Tumour growth was inhibited in 80% of experiments that used umbilical cord-derived MSCs, whereas tumour growth was promoted in 64% and 57% of experiments that used bone marrow- and adipose tissue-derived MSCs, respectively. This contrasting effect of MSCs on tumour growth observed under different experimental conditions may reflect differences in experimental design. This analysis calls for careful consideration of experimental design given the large number of MSC clinical trials currently underway.

Relaxation response of abdominal aorta to androgens in orchidectomised Sprague-Dawley rats fed a high-salt diet.

Previous studies have demonstrated the acute relaxant effects of androgens on normal arterial beds, but not on any with underlying or induced pathologies. This study investigated whether the status of the gonads affects the direct actions of androgens on isolated abdominal aorta from male Sprague-Dawley rats fed a high-salt diet. A high-salt diet reduced the relaxation response to exogenous testosterone, but not to dehydroepiandrosterone (DHEA). Orchidectomy reduced the relaxation response to both testosterone and DHEA, while testosterone replacement restored the acute vasorelaxant effect of testosterone and DHEA in both normal and high-salt diet fed rats. Gonadal status appears to be important in the acute vasorelaxant effect of androgens.

Differential responses to endothelial-dependent relaxation of the thoracic and abdominal aorta from male Sprague-Dawley rats.

Regional heterogeneity exists in reactivity of different vascular beds to vasoactive substances. Experiments were designed to determine if there are differences between thoracic and abdominal aorta response to acetylcholine-induced relaxation. Ten male Sprague-Dawley rats with a weighing between 200g-250g were used. The aorta was isolated and 3mm aortic rings were cut and suspended in organ baths containing physiological salt saline (PSS). Contractile and relaxation responses to noradrenaline (NA) and ACh, in the presence or absence of L-NNA and high K+ concentration were studied. Contractile response to NA was similar along the aorta. At the higher doses, ACh elicited a greater (p < 0.05) relaxation in the abdominal aorta when compared with the thoracic aorta. However, inhibition of eNOS was more effective (p<0.05) in preventing ACh-induced relaxation in the thoracic aorta when compared with the abdominal aorta. Conversely, inhibition of endothelial hyperpolarizing factor (EDHF) by high K+ concentration blocked ACh-induced relaxation to a greater extent in the abdominal aorta (p<0.05) when compared with the thoracic aorta. ACh-induced relaxation differs in the thoracic and abdominal aorta. Differences in the EDHF activity along the aorta underlie the differential response of the thoracic and abdominal aorta to ACh-induced relaxation.

Testosterone relaxes abdominal aorta in male Sprague-Dawley rats by opening potassium (K(+)) channel and blockade of calcium (Ca(2+)) channel.

AIM: To investigate the direct effect of testosterone and its precursor/derivative dehydroepiandrosterone (DHEA) on isolated rat abdominal aortic rings. MATERIALS AND METHODS: 3mm abdominal aortic rings that were obtained from 3 months old male Sprague-Dawley rats were suspended in organ baths containing Hepes buffered PSS bubbled with 100% oxygen. Relaxation response to testosterone and DHEA was studied in noradrenalin pre-contracted rings. The role of aromatase and androgen receptor was assessed by inhibition using aminogluthetemide and blockade using flutamide respectively. Relaxation responses of the rings to testosterone in the presence of l-NAME, indomethacin, barium chloride, apamin, charybdotoxin, iberiotoxin, and nifedipine were also determined. RESULTS: Both aromatase inhibition and androgen receptor blockade did not block the relaxing effect of testosterone on rings from rat abdominal aorta. Also there was no significant difference between testosterone relaxation response in the presence or absence of l-NAME and indomethacin. However 3µM, BaCl(2) almost completely abolished the aortic ring relaxation response to testosterone while 1µM, nifedipine potentiated the vasorelaxing effect of testosterone. CONCLUSION: Testosterone relaxes abdominal aorta directly via a non-genomic pathway which is independent of endothelial derived vasoactive substances, but involves activation of inward rectifying potassium channel (K(IR)) and blockade of l-type calcium channel.

Effect of methanol extract of Ricinus communis seed on reproduction of male rats.

AIM: To investigate the effect of methanol extract of Ricinus communis seed (RCE) on male rats reproductive functions. METHODS: Thirty-two male albino rats were divided into four groups. Groups 1, 2 and 3 were gavaged with 0.2 mL of 2.5% tween 80 (RCE vehicle; control) or 20 mg/(kg x d) and 40 mg/(kg x d) of RCE, respectively, for 30 days, and group 4 was also gavaged with 40 mg/(kg x d) of RCE, but was allowed a recovery period of 30 days. Five untreated female rats were cohabited with male rats in each group from day 25 of RCE treatment for 5 days, except group 4, where cohabitation began on day 25 of the recovery period. All male rats were sacrificed 24 h after the experiments. The female rats were laparotomized on day 19 of pregnancy and the number and weight of litters were recorded. RESULTS: There was a significant decrease (P<0.01) in the weight of the reproductive organs, sperm functions and serum levels of testosterone in RCE treated rats. There was disorganization in the cytoarchitecture of the testes, disruption of the seminiferous tubules and erosion of the germinal epithelium. The number and weight of litters of rats in groups 2 and 4 decreased significantly (P<0.05) but no changes were observed in group 3. RCE caused no changes in liver, kidney, heart or body weights in male rats. CONCLUSION: RCE has a reversible negative impact on male reproductive functions, which appears to be mediated via gonadal disruption in testosterone secretion.