Effect of rapid eye movement sleep deprivation during pregnancy on glucocorticoid receptor regulation of HPA axis function in female offspring.

Poor maternal sleep quality during the different phases of pregnancy acts as a prenatal stress and is critical for fetal development. Despite the potential adverse effects of maternal stress on the behavior and physiology of the offspring, the mechanisms remain poorly understood. The present study investigates the effects of maternal sleep deprivation (SD) at different stages of pregnancy on the hypothalamic-pituitary-adrenal (HPA) axis in female offspring. The pregnant rats were subjected to sleep deprivation of 12 h per day at different stages; early (ESD), mid (MSD), and late (LSD) stages, on pregnancy days 1-7, 8-14, and 14-20, respectively. At postnatal day 60, levels of corticosterone (CORT), hypothalamic corticotropin-releasing factor receptor 1 (CRF-R1), and hippocampal glucocorticoid receptors (GR) were evaluated in the offspring. Although the hypothalamic CRF-R1 level was increased in the offspring of SD dams, immunohistochemical staining showed reduced immunoreactivity of GR in ESD and LSD offspring hippocampal area. Altogether, the data suggests that a critical period for adverse effects of SD on the HPA axis in female offspring of Wistar rats may be during early and late pregnancy.

l-arginine Supplementation Increased Only Endothelium-Dependent Relaxation in Sprague-Dawley Rats Fed a High-Salt Diet by Enhancing Abdominal Aorta Endothelial Nitric Oxide Synthase Gene Expression.

BACKGROUND: Abnormal vascular reactivity and reduced expression of endothelial nitric oxide synthase (eNOS) gene are hallmark of salt-induced hypertension in rats. Although l-arginine is an established vasodilator, the mechanism by which it modulates vascular reactivity in salt-induced hypertension is not clearly understood. OBJECTIVES: This study was designed to investigate the mechanism by which oral l-arginine supplementation modulates vascular reactivity and eNOS gene expression in Sprague-Dawley rats fed a high-salt diet. METHODS: Forty-eight weaned male Sprague-Dawley rats of weight range 90 to 110 g were randomly divided into 6 groups of 8 rats per group. Group I was fed normal rat chow ad libitum and served as the Normal Diet group. Group II was fed a diet that contained 8% NaCl. Groups III and IV took normal and high-salt diet, respectively, and then received oral l-arginine supplementation (100 mg/kg/day), while groups V and VI took normal and high-salt diet, respectively, and then were co-administered with both l-arginine and l-nitro-arginine methyl ester (L-NAME; 100 mg/kg/day and 40 mg/kg/day, respectively) orally. At the end of 12-week experimental period, the animals were sacrificed to assess vascular reactivity and gene expression level. RESULTS: Our results show that high-salt diet significantly reduced (P < .05) endothelium-dependent relaxation response to acetylcholine and qualitatively reduced eNOS gene expression in the abdominal aorta of the rats. However, l-arginine supplementation improved the impaired endothelium-dependent relaxation and nitric oxide level while ameliorating the reduced eNOS gene expressions. CONCLUSION: This study suggests that oral supplementation of l-arginine enhances endothelial-dependent relaxation in rats fed a high-salt diet by ameliorating eNOS gene expression in the abdominal aorta of the rats.

Angiotensin receptor blockade with Losartan attenuates pressor response to handgrip contraction and enhances natriuresis in salt loaded hypertensive subjects: a quasi-experimental study among Nigerian adults.

INTRODUCTION: Sympathetic and Renin-Angiotensin-Aldosterone systems play crucial roles in blood pressure response to increased salt intake. This study investigated the effects of angiotensin receptor blocker (ARB) and sympathetic excitation on the responses of blood pressure (BP) and peripheral vascular resistance (PVR) in salt loaded normotensive (NT) and hypertensive (HT) Nigerian subjects. METHODS: 16 NT and 14 HT participants, that were age-matched [39.9 ± 1.3 vs 44.1±2.1yrs (P= 0.10)], underwent 5 days each of oral administration of 200mmol NaCl, and 200mmol NaCl + 50mg Losartan, preceded by a baseline control condition. BP and PVR responses to 30% Maximum Voluntary Contraction (MVC) of handgrip (HG) for one minute were determined at baseline, after salt load and after salt + Losartan. Data were presented as Mean ± SEM, and analyzed with two-way ANOVA and paired t-test, with P<0.05 accepted as significant. RESULTS: BP and PVR were significantly increased by HG at baseline, after salt load and after salt + Losartan in NT and HT. Salt load augmented the HG-induced SBP (P=0.04) and MABP responses (P=0.02) in HT. While Losartan attenuated the HG- induced Systolic Blood Pressure (SBP) SBP response (P=0.007) and DBP response (P=0.003) in HT and NT respectively after salt + Losartan. HG-induced PVR response was significantly accentuated after salt load in HT (P=0.005), but it was not significant in NT (P=0.38). CONCLUSION: The implication of our finding is that angiotensin II receptor blockade possibly attenuates salt-induced sympathetic nerve excitation in black hypertensive patients.

Oxidative status in rat kidney exposed to petroleum hydrocarbons.

OBJECTIVE: The study investigates the possible role of oxidative stress on renal tissues in association with petroleum hydrocarbon-induced nephrotoxicity. MATERIALS AND METHODS: Rats of comparable weights were randomly distributed into 10 groups: Control and groups exposed to kerosene, petrol, and diesel via inhalation, contamination by food, and contamination by water. The exposure lasted for eight weeks. RESULTS: Exposure to petroleum hydrocarbon led to significant rise in serum urea and creatinine, and renal tissue malondialdehyde. It also caused significant reduction in urinary urea and creatinine, and reduced glutathione, superoxide dismutase, and catalase activities of renal tissue homogenate. However, serum and urine concentrations of albumin and total protein were comparable in all groups. CONCLUSION: Results from this study shows that exposure to petroleum hydrocarbon led to renal dysfunction via oxidative stress, increasing lipid peroxidation and reducing the antioxidant defense mechanism.

Testosterone reduces vascular relaxation by altering cyclic adenosine monophosphate pathway and potassium channel activation in male Sprague Dawley rats fed a high-salt diet.

OBJECTIVES: Male gender and high-salt diet are risk factors for hypertension. The effect of chronic exposure to testosterone is an increase in vascular tone but its influence upon responses induced by other vasoactive agents is not clear. We considered the possibility of interactions between testosterone and a high-salt diet in the mechanisms that are involved in the regulation of vascular tone. Therefore, we designed experiments to assess the involvement of the cyclic adenosine monophosphate (cAMP) pathway and potassium channel activation on vascular relaxation elicited by testosterone deficiency that was induced by orchidectomy in Sprague Dawley rats on a normal or high-salt diet. METHOD: Weanling male rats were randomly divided into eight groups (n = 6 each) that were either orchidectomized or sham operated with or without testosterone replacement (10 mg/kg body weight of Sustanon 250 intramuscularly, Organon, Holland) and were placed on a normal or high-salt (0.3% or 8% NaCl) diet, respectively, for 6 weeks. Arterial blood pressure was determined before and weekly throughout the experiment using the tail-cuff method. Relaxation responses to forskolin and diazoxide were studied in noradrenaline (0.1 µM) precontracted aortic rings. RESULTS: There was an increase in the systolic blood pressure of rats placed on a high-salt diet compared with control or orchidectomized rats. Orchidectomy elicited a reduction in the systolic blood pressure while testosterone replacement restored systolic blood pressure to values seen in intact rats. A high-salt diet reduced the relaxation response to forskolin and diazoxide but not in orchidectomized rats while testosterone replacement re-established the blunted relaxation response to forskolin and diazoxide. CONCLUSION: Inhibition of potassium channel or adenylyl cyclase activation appears to contribute to the mechanisms by which a high-salt diet increases vascular tone. These effects were counteracted by orchidectomy in male Sprague Dawley rats.

Chronic angiotensin-II treatment potentiates HR slowing in Sprague-Dawley rat during acute behavioral stress.

This study examined the effect of 2-week infusion of angiotensin-II (Ang-II; 175 ng/kg/min) via minipump in rats (n=7) upon the mean arterial blood pressure (mBP) and heart rate (HR) response to an acute stress as compared to rats infused with saline (n=7). The acute stress was produced by a classical aversive conditioning paradigm: a 15s tone (CS+) followed by a half second tail shock. Baseline mBP in Ang-II infused rats (167.7±21.3 mm Hg; mean±SD) significantly exceeded that of controls (127.6±13.5 mm Hg). Conversely, baseline HR in the Ang-II infused rats (348±33) was significantly lower than controls (384±19 bpm). The magnitude of the mBP increase during CS+ did not differ between groups, but the HR slowing during CS+ in the Ang-II infused rats (-13.2±8.9 bpm) was significantly greater than that seen in controls (-4.2±5.5 bpm). This augmented bradycardia may be inferentially attributed to an accentuated increase in cardiac parasympathetic activity during CS+ in the Ang-II infused rats. The mBP increased above baseline immediately post-shock delivery in controls, but fell in the Ang-II infused rats, perhaps because of a 'ceiling effect' in total vascular resistance. This classical conditioning model of 'acute stress' differs from most stress paradigms in rats in yielding a HR slowing concomitant with a pressor response, and this slowing is potentiated by Ang-II.

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.

Extended longitudinal analysis of arterial pressure and heart rate control in unanesthetized rats with type 1 diabetes.

We recorded arterial pressure (BP) and heart rate (HR) in type-1 diabetic rats vs. controls for >6 months. Diabetic rats (DIAB) were maintained on insulin from the day glucose >250 mg/dl ("Day 0"). Weight was similar between groups until ~3 weeks before Day 0 when the weight in DIAB transiently lagged the controls (CONT); this difference was maintained throughout the study, but both groups otherwise gained weight in parallel. Plasma glucose attained 371 ± 109 (SD) mg/dl by day 1 in DIAB. Mean BP was similar across groups, and declined through the initial 4-6 months in both the CONT (at -0.06 ± 0.04 mmHg/day) and in the DIAB (at -0.14 ± 0.21 mmHg/day; NS vs. CONT). HR in the CONT (Month 1: 341 ± 13 bpm) exceeded DIAB (325 ± 25 bpm) through ~6 months after Day 0, and also decreased progressively over this period in CONT (-0.19 ± 0.14 bpm/day) and DIAB (-0.29 ± 0.23 bpm/day; NS vs. CONT) before leveling. The BP power within 0.35-0.45 Hz changed during the 90 min before vs. after the transition from dark to light, and light to dark; there were no between group differences. The slope of the log-log linear portion of the BP power spectrum between 1.0/h and 1/min was similar across groups, and increased in both from month 1 to month 6. Regulatory mechanisms maintain similar profiles in BP and HR in diabetic vs. control animals through the initial half year of the disease.

Exposure to petroleum hydrocarbon: implications in lung lipid peroxidation and antioxidant defense system in rat.

OBJECTIVE: Various studies have implicated automobile exhausts as risk factors in cardiovascular and pulmonary diseases; however, there is little or no documentation on the role of the main source of the exhausts, petroleum hydrocarbons, on cardiopulmonary pathologies. Thus, we investigated the effect of petroleum hydrocarbons, using various petroleum products, on histomorphology of the lung and the role of lipid peroxidation in it. MATERIALS AND METHODS: Control rats were not exposed to any of the petroleum products, whereas petrol-exposed, diesel-exposed, and kerosene-exposed rats were exposed to petrol, diesel, and kerosene by inhalation, respectively. RESULTS: Exposure to petroleum hydrocarbons significantly induced lipid peroxidation with a consequent rise in malondialdehyde (MDA), and a decrease in superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) level. Exposure to petroleum hydrocarbons also caused an alteration in the histomorphology of lung tissues. CONCLUSION: Our findings imply that exposure to petroleum hydrocarbons by inhalation is a risk factor in the pathophysiology of pulmonary dysfunction. This is associated with oxidative stress.

Longitudinal analysis of arterial blood pressure and heart rate response to acute behavioral stress in rats with type 1 diabetes mellitus and in age-matched controls.

We recorded via telemetry the arterial blood pressure (BP) and heart rate (HR) response to classical conditioning following the spontaneous onset of autoimmune diabetes in BBDP/Wor rats vs. age-matched, diabetes-resistant control (BBDR/Wor) rats. Our purpose was to evaluate the autonomic regulatory responses to an acute stress in a diabetic state of up to 12 months duration. The stress was a 15-s pulsed tone (CS+) followed by a 0.5-s tail shock. The initial, transient increase in BP (i.e., the "first component," or C(1)), known to be derived from an orienting response and produced by a sympathetic increase in peripheral resistance, was similar in diabetic and control rats through ∼9 months of diabetes; it was smaller in diabetic rats 10 months after diabetes onset. Weakening of the C(1) BP increase in rats that were diabetic for >10 months is consistent with the effects of sympathetic neuropathy. A longer-latency, smaller, but sustained "second component" (C(2)) conditional increase in BP, that is acquired as a rat learns the association between CS+ and the shock, and which results from an increase in cardiac output, was smaller in the diabetic vs. control rats starting from the first month of diabetes. A concomitant HR slowing was also smaller in diabetic rats. The difference in the C(2) BP increase, as observed already during the first month of diabetes, is probably secondary to the effects of hyperglycemia upon myocardial metabolism and contractile function, but it may also result from effects on cognition. The small HR slowing concomitant with the C(2) pressor event is probably secondary to differences in baroreflex activation or function, though parasympathetic dysfunction may contribute later in the duration of diabetes. The nearly immediate deficit after disease onset in the C(2) response indicates that diabetes alters BP and HR responses to external challenges prior to the development of structural changes in the vasculature or autonomic nerves.

Circadian Variations in Blood Pressure, Heart Rate, and HR-BP Cross-Correlation Coefficient during Progression of Diabetes Mellitus in Rat.

Circadian changes in cardiovascular function during the progression of diabetes mellitus in the diabetes prone rat (BBDP) (n = 8) were studied. Age-matched diabetes-resistant rats (BBDR) served as controls. BP was recorded via telemetry in contiguous 4 hr time periods over 24 hours starting with 12 midnight to 4 am as period zero (P0). Prior to onset of diabetes BP was high at P0, peaked at P2, and then fell again at P3; BP and heart rate (HR) then increased gradually at P4 and leveled off at P5, thereby exhibiting a bipodal rhythm. These patterns changed during long-term diabetes. The cross-correlation coefficient of BP and HR was not significantly different across groups at onset, but it fell significantly at 9 months of duration of diabetes (BBDP: 0.39 ± 0.06; BBDR: 0.65 ± 0.03; P < .05). These results show that changes in circadian cardiovascular rhythms in diabetes mellitus became significant at the late stage of the disease.