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.

The effect of hydro-alcoholic of Phoenix Dactylifera extract on sleep and EEG in rat.

OBJECTIVE: Hard envelope of date palm pollen is used as a sedative and calmative compounds in Iranian traditional medicine. We tried to study the effects of Phoenix dactylifera (Tarooneh) extract on sleep time and Brian waves. MATERIALS AND METHODS: Rats were divided into control and test groups in sleep experiment. Control groups included intact group (without any injection), negative control group (saline) and positive control group (midazolam 0.1 mg/kg). Test groups received three doses of Tarooneh extract (62.5, 125 and 250 mg/kg). Rat were placed in sleep physiograph system and recording started 20 min after 2-hr calming down. Four parameters including sleep time, awakening, most activity period and main sleep time interval were measured. In EEG experiment electrodes were placed under the cranium for EEG recording and waves were compared with their baselines. RESULTS: All doses of the extract increased sleeping time (p< 0.05) but just the dose of 250 mg/kg (p<0.05) and midazolam (p< 0.001) decreased the awakening time. EEG results showed that the dose of 125 mg/kg increased the low frequency waves (p< 0.05) and the dose of 250 mg/kg decreased high frequency waves of alpha and beta (p< 0.05). CONCLUSION: Due to these effect on sleeping time and EEG, Tarooneh extract consumption can be useful as a sedative agent in Iranian traditional medicine. According to this study, the doses of 125 and 250 mg/kg of the extract would be the appropriate doses to be further studied.

Role of 17-beta estradiol in baroreflex sensitivity in the nucleus tractus solitarii via the autonomic system in ovariectomized rats.

OBJECTIVE: To investigate the effect of estrogen exerted through the autonomic system in the nucleus tractus solitarii (NTS) on increasing the sensitivity of the baroreflex under conditions of acute hypertension in ovariectomized rats. METHODS: In this experimental study, conducted in Kerman University of Medical Sciences, Kerman, Iran from March 2010 to October 2010, 36 female rats were ovariectomized and then estrogen capsules were implanted beneath their skin. After 2 weeks, the left femoral vein and artery were cannulated for phenylephrine infusion and recording of mean arterial pressure and heart rate. Subsequently, atropine, propranolol, and saline were injected into the NTS, followed by measurements of changes in heart rate and changes in mean arterial pressure just prior to phenylephrine infusion. RESULTS: Estrogen increased the bradycardia response and inhibited the rise of mean arterial pressure; namely, after phenylephrine infusion, the change in heart rate was significantly lower in the estrogen-receiving group compared with the control group (p<0.05). Baroreflex sensitivity was significantly increased in the estrogen-receiving group compared with the control group (p<0.01). Baroreflex sensitivity was significantly attenuated in both groups (estrogen-receiving and control) after atropine injection, compared with after propranolol or saline injection (p<0.01). CONCLUSION: It is probable that under conditions of acute hypertension, estrogen affects the NTS through the parasympathetic system and enhances baroreflex sensitivity.

Effects of Low-dose Morphine on Nitric Oxide Concentration and Angiogenesis in Two-kidney One Clip Hypertensive Rats.

OBJECTIVES: We investigated the effects of low-dose morphine on nitric oxide (NO) and angiogenesis in two-kidney one clip hypertensive (2K1C) rats. MATERIALS AND METHODS: MALE RATS WERE DIVIDED INTO TWO GROUPS: sham-clip operated and 2K1C. Each group subdivided into saline and morphine (3 mg/kg i.p. 8 weeks) groups. Blood pressure, heart rate, plasma renin activity (PRA), NO concentration and murine matrigel angiogenesis were evaluated. RESULTS: Morphine had no effects on blood pressures and HR in sham normotensive rats but attenuated diastolic blood pressure (DBP) (P< 0.01) and mean arterial pressure (MAP) (P< 0.01) in 2K1C compared with saline. PRA level was significantly higher in 2K1C compared with sham groups (P< 0.01) but morphine decreased it in 2K1C compared with saline (P< 0.01). After clipping, NO in 2K1C hypertensive rats was decreased (P< 0.01) and morphine increased it compared with saline (P< 0.01). Morphine promoted angiogenesis in both sham (P< 0.01) and 2K1C (P< 0.0001) groups. CONCLUSION: Low-dose morphine stimulated angiogenesis in two-kidney one clip hypertensive rats probably via NO pathways.

The effect of repeated diazepam administration on myocardial function in the ischemia-reperfused isolated rat heart.

OBJECTIVE: To evaluate whether repeated diazepam administration affects the heart in ischemia-reperfusion. METHODS: This study was performed at the Medical Biology Research Center, Kermanshah, Iran, from March to September 2008. Four groups of rats were subjected to a daily injection of diazepam (group 1 [0.5 mg/kg for 21 days], group II [2.5 mg/kg for 5 days], and group III [5 mg/kg for 5 days] intraperitoneally), and saline solution (21 days) in the control groups. Isolated, perfused hearts were subjected to 40 minutes global ischemia, and 45 minutes reperfusion. The left ventricular developed pressure (LVDP), heart rate, and coronary flow were measured. Rate pressure product (RPP) was calculated. In reperfusion, released lactate dehydrogenase (LDH) enzyme in effluent was measured. RESULTS: It was observed that the recovery of the RPP and LVDP in reperfusion significantly decreased in the test group III (n=9) in comparison to the control (n=8). During the reperfusion period, the released LDH significantly increased in test group II (n=8) and group III in comparison with the control. CONCLUSION: The results show that repeated administration of diazepam (5 mg/kg for 5 days) reduced the cardiac performance in reperfusion, and significantly exacerbated the ischemia-reperfusion injury. It is probably mediated by the changing of cardiac susceptibility in ischemia due to repeated administration of diazepam.

Combination therapy of rosiglitazone, a peroxisome proliferator-activated receptor-gamma ligand, and NMDA receptor antagonist (MK-801) on experimental embolic stroke in rats.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists have been found to have potent anti-inflammatory actions and suggested as potential therapies for brain ischaemia. Glutamate is the most common excitatory neurotransmitter in the central nervous system and is released excessively during ischaemia. Stroke therapy will require combinations of drug classes, because no single drug class has yet been proven efficacious in human beings. The present study was conducted to assess whether N-methyl-d-aspartate (NMDA) receptor antagonist (MK-801) treatment can improve recovery from ischaemic brain injury and whether rosiglitazone, a PPAR-gamma ligand, can increase its neuroprotective effect in an embolic model of stroke. Stroke was induced in rats by embolizing a preformed clot into the middle cerebral artery. Rosiglitazone (0.1 mg/kg, intraperitoneally) and MK-801 (0.1 mg/kg, intravenously) were injected immediately after embolization. Forty-eight hours later, the brains were removed, sectioned and stained with triphenyltetrazolum chloride and analysed by a commercial image processing software programme. Rosiglitazone and MK-801 alone or in combination decreased infarct volume by 49.16%, 50.26% and 81.32%, respectively (P < 0.001). Moreover, the combination therapy significantly decreased the infarct volume when compared to any drug used alone (P < 0.05). MK-801 reduced the brain oedema by 68% compared to the control group (P < 0.05), but rosiglitazone or combination did not show any significant effect. The drugs alone or in combination also demonstrated improved neurological function, but combination therapy was more effective on neurological deficits improving. Our data show that the combination of MK-801 and rosiglitazone is more neuroprotective in thromboembolic stroke than given alone; this effect perhaps represents a possible additive effect in the brain infarction.

Involvement of hypothalamic pituitary adrenal axis on the analgesic cross-tolerance between morphine and nifedipine.

Bidirectional cross-tolerance develops between opioids and Ca(2+) channel blockers relating to their antinociceptive effects; however, the role of hypothalamic pituitary adrenal (HPA) axis on this action has not been elucidated yet. We examined the analgesic cross-tolerance between morphine and nifedipine, a dihydropyridine calcium channel blocker, in intact and adrenalectomized (ADX) rats and also evaluated modification of HPA activity during this phenomenon. The tail-flick test was used to assess the nociceptive threshold. The plasma level of corticosterone, as a marker of HPA function, was measured by radioimmunoassay. Our results showed that, in sham operated rats which were chronically treated with morphine, nifedipine failed to affect nociceptive threshold but it could induce significant antinociceptive effect in ADX morphine treated animals. This effect was reversed by corticosterone replacement. Furthermore, morphine could not induce analgesic effect either in sham operated or in ADX animals that received chronic nifedipine. Chronic morphine inhibited the effect of nifedipine on corticosterone secretion but nifedipine treatment had no effect on morphine-induced corticosterone secretion. Based on these results, we can conclude that HPA axis is involved in the induction of cross-tolerance between morphine and nifedipine due to chronic morphine and not nifedipine treatment.

Treadmill running reverses retention deficit induced by morphine.

Human and animal studies have suggested that exercise has benefits overall health and cognitive function. The aim of this study was to investigate the effect of treadmill running on passive avoidance learning and memory deficit in morphine-treated rats. The passive avoidance learning was measured in different time intervals (1, 2 and 24 h as well as 1 week and 1 month). Four groups of rats were included as follows: control, morphine-treated, exercised-saline and exercised-morphine-treated group. The electrical foot shock and treadmill training (2 h at a speed of 5 m/min for 10 days) were applied for all the groups. The data obtained was analyzed using unpaired Students t-test and ANOVA test with group as the independent variable, and performance in each session (avoidances and crossings) as the dependent variables. The results show that the total time staying in dark box was decreased in exercised-saline and exercised-morphine-treated rats by treadmill running (P<0.05). The avoidance learning was significantly reduced in morphine-treated group as indicated by the increased total time of staying in the dark box compared with the control group (P<0.05). We could conclude that exercise increased the delay time of entry to the dark electrical foot shock box, suggesting that morphine impaired the short-term memory and learning and this was reversed by the treadmill running.

Nifedipine potentiates antinociceptive effects of morphine in rats by decreasing hypothalamic pituitary adrenal axis activity.

It has been shown that nifedipine, as a calcium channel blocker can potentiate the antinociceptive effect of morphine; however, the role of Hypothalamic-Pituitary-Adrenal (HPA) axis on this action has not been elucidated. We examined the effect of nifedipine on morphine-induced analgesia in intact and adrenalectomized (ADX) rats and on HPA activity induced by morphine. To determine the effect of nifedipine on morphine analgesia, nifedipine (2 mg/kg i.p.) that had no antinociceptive effect, was injected concomitant with sub-effective dose of morphine (1 and 2 mg/kg). The tail-flick test was used to assess the nociceptive threshold, before and 15, 30, 60, 90, 120 and 180 min after drug administration. Our results showed that, nifedipine could potentiate the antinociceptive effect of morphine and this effect of nifedipine in ADX was greater than sham operated rats which, was reversed by corticosterone replacement. Nifedipine has an inhibitory effect on morphine -induced corticosterone secretion. Thus, the data indicate that the mechanism underlying the potentiation of morphine analgesia by nifedipine involves mediation, at least in part, by attenuating the effect of morphine on HPA axis.