The denervation or activation of renal sympathetic nerve and renal blood flow.

The denervation or activation of the sympathetic nerve in the kidney can affect renal hemodynamics. The sympathetic nervous system regulates the physiological functions of the kidneys. Stimulation of sympathetic efferent nerves affects various parameters related to renal hemodynamics, including sodium excretion, renin secretion, and renal blood flow (RBF). Hence, renal sympathetic fibers may also play an essential role in regulating systemic vascular resistance and controlling blood pressure. In the absence of renal nerves, the hemodynamics response to stimuli is negligible or absent. The effect of renal sympathetic denervation on RBF is dependent on several factors such as interspecies differences, the basic level of nerve activity in the vessels or local density of adrenergic receptor in the vascular bed. The role of renal denervation has been investigated therapeutically in hypertension and related disorders. Hence, the dynamic impact of renal nerves on RBF enables using RBF dynamic criteria as a marker for renal denervation therapy.

The role of Mas receptor on renal hemodynamic responses to angiotensin II administration in chronic renal sympathectomized male and female rats.

Background and purpose: Renal hemodynamics is influenced by renal sympathetic nerves and the renin-angiotensin system. On the other hand, renal sympathetic denervation impacts kidney weight by affecting renal hemodynamics. The current study evaluated the role of the Mas receptor on renal hemodynamic responses under basal conditions and in response to angiotensin II (Ang II) in chronic renal sympathectomy in female and male rats. Experimental approach: Forty-eight nephrectomized female and male rats were anesthetized and cannulated. Afterward, the effect of chronic renal sympathectomy was investigated on hemodynamic parameters such as renal vascular resistance (RVR), mean arterial pressure (MAP), and renal blood flow (RBF). In addition, the effect of chronic sympathectomy on kidney weight was examined. Findings/Results: Chronic renal sympathectomy increased RVR and subsequently decreased RBF in both sexes. Renal perfusion pressure also increased after sympathectomy in male and female rats, while MAP did not change, significantly. In response to the Ang II injection, renal sympathectomy caused a greater decrease in RBF in all experimental groups, while it did not affect the MAP response. In addition, chronic sympathectomy increased left kidney weight in right nephrectomized rats. Conclusion and implications: Chronic renal sympathectomy changed systemic/renal hemodynamics in baseline conditions and only renal hemodynamics in response to Ang II administration. Moreover, chronic sympathectomy increased compensatory hypertrophy in nephrectomized rats. These changes are unaffected by gender difference and Mas receptor blocker.

Renal Denervation Influences Angiotensin II Types 1 and 2 Receptors.

The sympathetic and renin-angiotensin systems (RAS) are two critical regulatory systems in the kidney which affect renal hemodynamics and function. These two systems interact with each other so that angiotensin II (Ang II) has the presynaptic effect on the norepinephrine secretion. Another aspect of this interaction is that the sympathetic nervous system affects the function and expression of local RAS receptors, mainly Ang II receptors. Therefore, in many pathological conditions associated with an increased renal sympathetic tone, these receptors' expression changes and renal denervation can normalize these changes and improve the diseases. It seems that the renal sympathectomy can alter Ang II receptors expression and the distribution of RAS receptors in the kidneys, which influence renal functions.

Comparing the effects of crocin at different doses on excitability and long-term potentiation in the CA1 area, as well as the electroencephalogram responses of rats under chronic stress.

Stress adversely affects the cellular and electrophysiological mechanisms of memory; however, crocin has beneficial effects on brain functions. Nonetheless, the electrophysiological effects of using this active saffron component at different doses are not yet studied in rats under chronic restraint stress. Therefore, this study compared the impact of crocin at different doses on the excitability and long-term potentiation (LTP) in the CA1 area of rats, as well as their electroencephalogram (EEG) responses, hippocampal and frontal cortical glucose levels under chronic restraint stress (an emotional stress model). Forty rats were allocated into five groups of control, sham, restraint stress (6 h/day/21 days), and two stress groups receiving intraperitoneal injections of crocin (30, 60 mg/kg/day). Besides measuring the slope and amplitude of field excitatory postsynaptic potentials (fEPSPs) in the input-output and LTP curves, the EEG waves and hippocampal and frontal cortical glucose levels were assessed in all groups. Chronic restraint stress significantly decreased the fEPSP slope and amplitude in the input-output curves and after LTP induction. Both doses of crocin (60 and particularly 30 mg/kg) significantly improved fEPSP slope and amplitude in the stressed groups. Also, stress and crocin only at a dose of 30 mg/kg altered the EEG waves. Hippocampal and frontal cortical glucose levels displayed no significant differences in the experimental groups. Crocin at doses of 60 mg/kg/day and particularly 30 mg/kg/day reversed the harmful effects of chronic restraint stress on LTP as a cellular memory-related mechanism. However, only the lower dose of crocin affected the electrical brain activity in EEG.

Hydroalcoholic Tarooneh Extract (Spathe of Phoenix Dactylifera) Increased Sedative-hypnotic Effects and Modulated Electroencephalography Brain Waves in Anesthetized Rats.

BACKGROUND: Spathe of phoenix dactylifera is hard-covering envelope of date palm which is mentioned as a nerve relief in ancient medicine books. In this experiment, three extract doses used in sleeping time, sedative efficacy, and electroencephalography (EEG) protocol to show different aspects of extract effects on sleep. MATERIALS AND METHODS: In three sleeping time, anesthesia time and EEG experiment protocols test group containing three extract doses (62.5, 125, and 250 mg/kg) were compared with saline control group, and in sleeping time experiment control group contained intact, midazolam, and saline group to detail more in behavioral Angel method. RESULTS: Three extract doses increased sleeping time when compared with saline control group (P < 0.05). In evaluated sedative efficacy, two 125 and 250 mg/kg doses increased anesthesia and showed sedative effect (P < 0.05). In EEG experiment, dose 125 mg/kg increased delta waves and decreased high-frequency waves of alpha and beta. In addition, there were significant decreases in alpha waves of 62.5 and 250 mg/kg doses. CONCLUSION: Although all three doses increased sleeping time, dose 125 mg/kg is more efficient for deep and relaxing sleep and suits more for related researches.

The Effect of Sneezing on the Reduction of Infarct Volume and the Improvement of Neurological Deficits in Male Rats.

BACKGROUND: Sneezing transiently elevates cerebral blood flow. We speculated that induced sneezing, following embolism would restore arterial flow, thereby diminishing infarct volume and improving neurological deficits. MATERIALS AND METHODS: Male rats were subjected to middle cerebral artery occlusion (MCAO) using prepared clots (embolization) and randomized into four equal groups as follows: (1) pre-MCAO-induced sneezing (PRMIS), (2) post-MCAO-induced sneezing (POMIS), and (3) pre- and POMIS (PRPOMIS) and the control group (eight rats per group). In the treatment groups, rats' sneezing episodes were induced before MCAO in PRMIS group or before regaining consciousness from surgical anesthesia in other treatment groups by cutting their whiskers during their anesthesia and subsequently inserted them into the rats' nostrils. Infarct volume was evaluated by 2, 3, 5-triphenyl tetrazolium chloride staining, and neurological deficits and brain edema were assessed by Bederson scale deficit scores 24-h post-MCAO. RESULTS: The infarct volume and brain edema reduced and neurological deficits improved in the induced sneezing groups as compared with the MCAO control group. Compared to the control group, the highest improvements in the infarct volume and neurological deficits were seen in the PRPOMIS group, and POMIS group showed the most significant differences concerning the results of both ischemic and nonischemic brain edema. The highest protective effect was observed in the central region of the MCA territory. CONCLUSIONS: The reduction in ischemia-induced brain injury, brain edema, and neurological deficits by sneezing suggest that brief episodes of acute hypertension after stroke can increase blood flow to the ischemic area and improve recovery.

Effects of Crocin on Learning and Memory in Rats Under Chronic Restraint Stress with Special Focus on the Hippocampal and Frontal Cortex Corticosterone Levels.

BACKGROUND: Chronic stress adversely influences brain functions while crocin, as an effective component of saffron, exhibits positive effects on memory processes. This study investigated the effects of different doses of crocin on the improvement of learning and memory as well as corticosterone (CORT) levels in the hippocampus and frontal cortex of rats subjected to chronic stress. MATERIALS AND METHODS: Forty male rats were randomly allocated to five different groups (n = 8): Control, sham; stress (6 h/day for 21 days) groups, and two groups receiving daily intraperitoneal injections of one of two doses (30 and 60 mg/kg) of crocin accompanied by 21 days of restraint stress. Latency was evaluated as a brain function using the passive avoidance test before and one-day after a foot shock. CORT levels were measured in the homogenized hippocampus and frontal cortex. RESULTS: Results revealed that chronic stress had a significantly (P < 0.01) negative effect on memory. Crocin (30 and 60 mg/kg), however, gave increase to significantly (P < 0.01 and P < 0.05; respectively) improved memory functions in the stressed rats. Furthermore, the CORT levels in the hippocampus and frontal cortex declined significantly (P < 0.05) in the stress group compared to the control. Only a crocin dose of 30 mg/kg was observed modulate significantly (P < 0.05) the CORT levels in the hippocampus and frontal cortex in the stressed group. CONCLUSIONS: It was found that the lower crocin dose (30 mg/kg) had more beneficial effects than its higher (60 mg/kg) dose on learning and memory under chronic stress conditions. Moreover, it was speculated that different doses of crocin act on different neurotransmitters and biochemical factors in the brain.

The influence of electrical stimulation on dorsal raphe nucleus with different current intensities on morphine-induced conditioned place preference in male rats.

INTRODUCTION: The dorsal raphe nucleus (DRN) influences a wide range of behavioral and physiological processes. The purpose of the present study was to test the effects of electrical stimulation of the DRN with different current intensities on morphine-induced conditioned place preference (CPP). MATERIALS AND METHODS: Male Wistar rats were divided for experimental groups (n=7). Stimulating electrodes were stereotaxically implanted into the DRN in anesthetized rats. We investigated the influences of electrical stimulation of the DRN with different current intensities with ineffective and effective dose of morphine (0.5 and 2.5mg/kg, respectively) on morphine-induced CPP. RESULT: Subcutaneous administration of morphine 2.5mg/kg produced significant CPP in comparison with saline group. The stimulation of the DRN with different current intensities (10, 25, 50 and 100µA) in combination with an effective dose of morphine did not show significant differences on acquisition phases, whereas there were significant decreases on expression phases versus to the morphine group on CPP only in current intensity 100µA. The stimulation of the DRN with different current intensities in combination with an ineffective dose of morphine showed significant increases in current intensities (50 and 100µA) on acquisition phases of CPP, but did not show significant differences on expression phases versus to the morphine group on CPP. CONCLUSION: It is possible that electrical stimulation of the DRN with changes in concentration of serotonin or involving other transmitters such as glutamate and GABA would be involved with these changes of CPP.

Effects of Temporary Inactivation and Electrical Stimulation of the Dorsal Raphe Nucleus on Morphine-induced Conditioned Place Preference.

BACKGROUND: The dorsal raphe nucleus (DRN) influences a wide range of behavioral and reward function. In this study, we evaluated electrical stimulation and inactivation of DRN on morphine conditioned place preference (CPP). METHODS: The rats were anesthetised (n = 7 for each group) and the electrode and cannula were implanted into the DRN by stereotaxic instrument. Electrical stimulation (100µA) and reversible inactivation by lidocaine were induced into DRN and then morphine-induced CPP was investigated. RESULTS: The stimulation of DRN in combination with effective dose of morphine showed a significant decrease only on expression phases 20s (SD 33.7) when compared with morphine group 119.85s (SD 23.7) (One way ANOVA, Tukey's; P = 0.036). Also, this stimulation in combination with ineffective dose of morphine showed a significant increase only on acquisition phases 67.5s (SD 41.2) of CPP compared with morphine group -46s (SD 18.51) (P = 0.034). Also, there were not significant differences in inactivation of DRN by lidocaine on different phase of CPP (P = 0.091) CONCLUSION: It is possible that electrical stimulation of the DRN with changes in concentration of serotonin or involving other transmitters such as glutamate and gamma amino butyric acid (GABA) would be involved to these changes of CPP.

The effect of intra-ventral hippocampus administration of TRPV1 agonist and antagonist on spatial learning and memory in male rats.

BACKGROUND: The role of transient receptor potential vanilloid 1 (TRPV1) in peripheral nervous system has been studied well but its role in the central nervous system remains to be studied in detail. The expression of TRPV1 receptors in hippocampus is suggesting that they may play an important role in higher cognitive functions such as learning and memory. METHODS: In the present study, the role of TRPV1 receptors in acquisition and retrieval of spatial memory of male Wistar rats was evaluated by intra-ventral hippocampus administration of TRPV1 selective agonist (OLDA) and antagonist (AMG9810) using Morris water maze. RESULTS: The results demonstrated that administration of either OLDA (0.001, 0.01 and 0.1 µg/rat) or AMG9810 (0.003, 0.03 and 0.3 µg/rat) did not influence memory acquisition or retrieval. CONCLUSIONS: These data suggest that ventral-hippocampal TRPV1 receptors possibly are not involved in spatial learning and memory.

Regulatory effects of chronic low-dose morphine on nitric oxide level along with baroreflex sensitivity in two-kidney one-clip hypertensive rats.

INTRODUCTION: Opiates are traditionally used for treatment of some acute heart disorders. There are only few reports on the effects of long-term treatment of cardiovascular diseases with morphine. This study aimed to investigate the effects of chronic low-dose morphine use on the cardiovascular system in two-kidney one-clip (2K1C) hypertensive rats. MATERIALS AND METHODS: Male Wistar rats were divided into two groups as the sham and 2K1C groups and each group was further subdivided into saline and morphine treatment subgroups. Blood pressure, heart rate, plasma rennin activity, serum nitric oxide concentration, and baroreflex sensitivity were measured. RESULTS: Morphine significantly attenuated systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the 2K1C animals. In addition, morphine decreased plasma rennin activity in the 2K1C group. Serum concentrations of nitric oxide were also decreased, and morphine prevented the reduction of nitric oxide. The baroreflex sensitivity was also improved following morphine administration in the 2K1C group. CONCLUSIONS: According to the results presented in this study, chronic administration of low-dose morphine reduces regulated hypertension in the 2K1C rats, probably via a nitric oxide-dependent pathway.

Involvement of ß-adrenergic receptor of nucleus tractus solitarius in changing of baroreflex sensitivity by estrogen in female rats.

BACKGROUND: Arterial baroreflex (ABR) is an important factor in preventing of blood pressure fluctuations that determined by baroreflex sensitivity (BRS). Estrogen is an ovarian hormone that has influence on ABR. The mechanism of this effect of estrogen unknown and may be mediated by ß-adrenergic receptor of nucleus tractus solitarius (NTS), an important area in regulation of baroreflex. Therefore, in this study changing of BRS by estrogen after blockade ß-adrenergic receptor of NTS in ovariectomized rats (Ovx) and Ovx treated with estrogen (Est) was examined. MATERIALS AND METHODS: After ovariectomy, all female rats divided to Ovx and Ovx + Est groups and two series of experiments were performed. In the first experiment, phenylephrine was [intravenously, IV] injected in both the Ovx and Ovx + Est groups, and mean arterial pressure (MAP), heart rate (HR), and BRS were evaluated (n = 8 for each group). In the second experiment, each of Ovx and Ovx + Est groups divided into saline and propranolol (pro) groups, saline and pro stereotaxically were microinjected into NTS, respectively. Further, phenylephrine (IV) was injected in all groups and BRS was evaluated. RESULTS: BRS significantly increased in estrogen-treated groups (Ovx + Est) compared to Ovx groups (P < 0.01). The blockade ß-adrenergic receptor of NTS by pro did not significantly changed BRS in both Ovx and Ovx + Est groups. CONCLUSION: We concluded that there aren't any intraction between estrogen and ß-adrenergic receptor of NTS in BRS.

Effect of co-administration of morphine and nicotine on cardiovascular function in two-kidney one clip hypertensive (2K1C) rats.

Cardiovascular morbidity and mortality are potentiated with smoking and hypertension. The aim of this study was to investigate the effects of morphine and nicotine co-administration on cardiovascular function in two-kidney one-clip hypertensive (2K1C) rats. Thirty-two male rats were divided into four groups as follow: Vehicle, morphine, nicotine and nicotine + morphine. All drugs were administered for 8 weeks. Baroreflex sensitivity (BRS), heart rate and blood pressure were measured using a Power Lab data acquisition. Plasma rennin activity (PRA) and serum concentration of nitric oxide (NO) were measured using Elisa method. To induce hypertension, the renal artery of left kidney was clipped for 8 weeks. A significant decrease in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) was observed in nicotine + morphine group compared to vehicle and nicotine groups (p<0.05). Serum concentration of NO was lower in nicotine + morphine group compared to morphine group and significantly higher than nicotine group. The BRS was lower in the nicotine + morphine group compared to other groups. The PRA level was higher in nicotine + morphine compared to morphine group but it was higher than nicotine group. This study demonstrated that prolonged co-consumption of morphine and nicotinedecreased PRA and blood pressure and increased the serum concentration of NO in hypertensive rats. Co-administration of morphine and nicotine decreased BRS in 2k1c hypertensive rats probably via central nervous system.

Role of cuneiform nucleus in regulation of sympathetic vasomotor tone in rats.

The cuneiform nucleus (CnF) is a sympathoexcitatory area involved in the central cardiovascular regulation. Its role in the maintaining vasomotor tone has, however, not yet been clarified. In the present study the effects of cobalt chloride (CoCl(2)) a nonselective synapse blocker and NMDA and non-NMDA glutamate receptors on resting mean arterial blood pressure and heart rate of CnF have been evaluated. CoCl(2), AP5 (an NMDA receptor antagonist) and CNQX (an AMPA/kinase receptor antagonist) (100nl) were microinjected into the CnF of anesthetized rats. The blood pressure and heart rate were recorded throughout the experiment. The responses of blood pressure and heart rate were compared with the pre-injection (paired t-test) and control (independent t-test) values. Microinjection of CoCl(2), AP5 and CNQX did not change the basal blood pressure and heart rate. In conclusion, our present study indicates that the CnF is not important in the regulation of cardiovascular tone.

Coronary angiogenesis during experimental hypertension: is it reversible?

BACKGROUND: We investigated coronary angiogenesis and serum vascular endothelial growth factor (VEGF) and its soluble receptor-1 (sFlt-1) concentrations in two-kidney one-clip (2K1C) hypertensive rats before and after reversal of hypertension. METHODS: THE ANIMAL GROUPS WERE: (i) sham-clipped for 12 weeks; (ii) 2K1C for 12 weeks; (iii) sham-clipped for 12 weeks and unclipped for 12 weeks; and (iv) 2K1C for 12 weeks and unclipped for 12 weeks. Blood samples were taken before experiments and after clipping and unclipping; capillary density was also evaluated. RESULTS: Our results showed that blood pressure in hypertensive animals was higher than sham group (175 ± 10 vs. 110.3 ± 11.3 mmHg; p < 0.05). Unclipping significantly reduced blood pressure in hypertensive rats (p < 0.05). Serum VEGF and sFlt-1 levels in hypertensive group were significantly lower than sham group (VEGF: 74.36 ± 5.85 vs. 104.07 ± 7.75 pg/ml; sFlt-1: 426.67 ± 25.74 vs. 690.76 ± 41.14 pg/ml, respectively; p < 0.05). Unclipping in hypertensive animals increased serum VEGF and sFlt-1 concentrations (VEGF: 93.65 ± 8.61 vs. 74.36 ± 5.85 pg/ml; sFlt-1: 742.05 ± 79.23 vs. 426.67 ± 25.74 pg/ml, respectively; p < 0.05). In hypertensive animals, capillary density in the heart was higher than sham group, non-significantly (p > 0.05) and after unclipping, it reached to sham group level. CONCLUSIONS: It seems that changes in capillary density and serum VEGF and sFlt-1 concentrations in renovascular hypertension are reversible by removing the cause of hypertension and it shows the importance of early diagnosis and treatment of hypertension in clinical condition.

Effect of acute and chronic hypertension on short- and long-term spatial and avoidance memory in male rats.

It has been demonstrated that hypertension can lead to coronary heart disease, heart failure, stroke, and memory loss. In this study we investigated the effect of acute and chronic hypertension on the avoidance and spatial learning and memory in rats. The forty male rats were divided into acute hypertensive, chronic hypertensive and control for each group rats. Hypertension was induced by Deoxy Corticosterone Acetate (DOCA)-salt method. DOCA was injected 30mg/kg of body weight subcutaneously, twice a week. These rats received NaCl 1% instead of tap water for drinking throughout the experiment. The control group received normal saline injection with usual drinking water. Spatial learning and memory was investigated by Morris water maze test and passive avoidance learning by Shuttle box test in the rats after hypertension induction. Results showed that acute hypertension impaired short-term memory in passive avoidance learning. However, acute and chronic hypertension did not affect spatial learning and memory. These data suggest that simple uncomplicated hypertension does not remarkably alter cognition.