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.

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.

Effect of oral magnesium sulfate administration on lectin-like oxidized low-density lipoprotein receptor-1 gene expression to prevent atherosclerosis in diabetic rat vessels.

AIMS/INTRODUCTION: The purpose of the present study was to investigate the possible effect of oral magnesium sulfate (MgSO4 ) in the reduction of atherosclerosis plaques through inhibition of lectin-like low-density lipoprotein receptor-1 (LOX-1) gene expression in diabetic vessels. MATERIALS AND METHODS: A total of 50 rats were divided into five groups, including non-diabetic control, Mg-treated non-diabetic control, chronic diabetic, Mg-treated chronic diabetic and insulin-treated chronic diabetic. The induction of diabetes was carried out by streptozotocin. The Mg-treated chronic diabetic and Mg-treated non-diabetic control groups were treated with 10 g/L of MgSO4 added to their drinking water. The insulin-treated chronic diabetic group received 2.5 U/kg of insulin twice per day. The fasting blood glucose level and bodyweight were determined weekly. Blood pressure measurement and the intraperitoneal glucose tolerance test were carried out after 16 weeks, and the plasma levels of Mg, lipid profile and oxidized low-density lipoprotein cholesterol (oxLDL) were determined. The mesenteric bed was isolated and perfused according to the McGregor method. The aorta was isolated for LOX-1 genes and proteins expression, and pathological investigation. RESULTS: MgSO4 administration improved blood pressure, sensitivity to phenylephrine, intraperitoneal glucose tolerance test, lipid profile and plasma ox-LDL level, and also lowered the blood glucose level to the normal range, and decreased LOX-1 gene and protein expressions. Insulin decreased blood pressure, sensitivity to phenylephrine, blood glucose, lipid profiles and plasma oxLDL level, but it did not decrease LOX-1 gene and protein expressions. CONCLUSIONS: The present findings suggested that MgSO4 improves blood pressure and vessel structure through decreasing oxLDL, and LOX-1 gene and protein expressions; however, insulin did not repair vessel structure, and LOX-1 gene and protein expressions.

Effect of Long-term Administration of Oral Magnesium Sulfate and Insulin to Reduce Streptozotocin-Induced Hyperglycemia in Rats: the Role of Akt2 and IRS1 Gene Expressions.

The effects of long-term oral administration of magnesium sulfate and insulin on hyperglycemia were investigated using Akt2 and IRS1 gene expression methods in streptozotocin-induced diabetic rats. Fifty rats were randomly divided into five experimental groups: 1, non-diabetic control (NDC); 2, Mg2+-treated non-diabetic control (Mg-NDC); 3, chronic diabetic (CD); 4, Mg2+-treated chronic diabetic (Mg-CD); and 5, insulin-treated chronic diabetic (Ins-CD). Streptozotocin was used to induce diabetes. The Mg-CD and Mg-NDC groups received 10 g/l of MgSO4 added to drinking water. The Ins-CD group received 2.5 U/kg of insulin twice a day. Blood glucose level and body weight were measured every week. The intraperitoneal glucose tolerance test (IPGTT) was performed after 16 weeks. MgSO4 administration improved the blood glucose level and IPGTT. It also increased Akt2 and IRS1 genes as well as protein expression. Insulin lowered the blood glucose level and increased IRS1 gene and protein expression, but did not affect Akt2 gene and protein expression. Glucose reduction after Mg therapy may be mediated, at least partially, via IRS1 and Akt2 genes and protein stimulation. In insulin-treated rats, insulin resistance was not significant due to the absence of Akt2 gene expression.

Effect of oral magnesium sulfate administration on blood glucose hemostasis via inhibition of gluconeogenesis and FOXO1 gene expression in liver and muscle in diabetic rats.

The present study was designed to investigate the possible role of Mg2+ in suppression of phosphoenolpyruvate carboxy kinase (PEPCK) enzyme via inhibition of FOXO1gene expression in liver and we also examined whether Mg contributes to decrease blood glucose in muscle via inhibiting FOXO1 gene and protein expression. Fifty rats in five groups of experiment were considered as; non-diabetic control (NDC), Mg2+-treated non-diabetic control (Mg2+-NDC), chronic diabetic (CD), Mg2+-treated chronic diabetic (Mg2+-CD), and insulin-treated chronic diabetic (Ins-CD). Streptozotocin (STZ) was used for diabetes induction. The Mg2+-CD and Mg2+-NDC groups received 10 g/l of magnesium sulfate (MgSO4) added to drinking water, and Ins-CD group received 2.5 U/kg of insulin. The blood glucose level and body weight were measured weekly. After 16 weeks, intraperitoneal glucose tolerance test (IPGTT) was done and blood samples were taken to determine the plasma levels of Mg and gastrocnemius muscle legs, and liver were isolated for both Forkhead transcription factor (FOXO1) and PEPCK enzyme genes and proteins expression. Administration of MgSO4 improved IPGTT, lowered blood glucose levels and decreased FOXO1 and PEPCK genes and proteins expression in muscle and liver, while insulin just could decrease FOXO1 gene and protein expression in the muscle. These findings illustrated that MgSO4 improved hyperglycemia via inhibition of FOXO1 gene and protein level in the muscle and liver, and it also decreased blood glucose level by prohibition of gluconeogenesis pathway in the liver. However, long time administration of insulin did not have any effect on liver.

The role of PPAR-γ and NFKB genes expression in muscle to improve hyperglycemia in STZ-induced diabetic rat following magnesium sulfate administration.

The present study was designed to investigate the possible role of magnesium (Mg2+) on activation of the peroxisome proliferator-activated receptor gamma (PPAR-γ) and inhibition of nuclear factor-KB (NFKB p65) in muscle to increase glucose transporter 4 (GLUT4) gene expression. Fifty rats were divided into five groups, namely non-diabetic control (NDC), Mg2+-treated non-diabetic control (Mg2+-NDC), chronic diabetic (CD), Mg2+-treated chronic diabetic (Mg2+-CD), and insulin-treated chronic diabetic (Ins-CD). Diabetes was induced with streptozotocin (STZ) injection. The Mg2+-CD and Mg2+-NDC groups received 10 g/l of magnesium sulfate (MgSO4) added to drinking water and Ins-CD group received 2.5 U/kg of insulin. The blood glucose level and body weight were measured every week. After 16 weeks, intraperitoneal glucose tolerance test (IPGTT) was done and then animals were decapitated, blood samples were taken to determine the plasma levels of Mg2+ and gastrocnemius muscle legs were isolated for both PPAR-γ and NFKB (p65) genes and proteins expression. Administration of MgSO4 improved IPGTT, lowered blood glucose levels and increased PPAR-γ gene and protein expression. Diabetes increased NFKB gene and protein expression. Although Mg2+ therapy could not decrease NFKB (p65) gene expression, the protein decreased by Mg2+ therapy. Insulin decreased NFKB (p65) gene and protein expression, without any effect on PPAR-γ gene and protein expression. According to our findings it seems that suppressing NFKB (p65) protein synthesis and increases in PPAR-γ gene and protein expression could help Mg2+ administration to decreases blood glucose levels. But decreasing in NFKB (p65) gene and protein expression help insulin to decrease blood glucose level.

Vasopressin and sympathetic systems mediate the cardiovascular effects of the GABAergic system in the bed nucleus of the stria terminalis.

The bed nucleus of the stria terminalis (BST) is an important part of the limbic system. It has been shown that chemical stimulation of the BST elicited cardiovascular depressive and bradycardic responses. It was also demonstrated that GABA is present in the BST, though its role in cardiovascular control is not yet understood. This study was performed to find the effects of GABA receptor subtypes in the BST on cardiovascular responses and to find the possible mechanisms that mediate these responses in urethane-anesthetized rats. Microinjection of muscimol (500 pmol/100 nl), a GABA(A) agonist, into the BST produced a weak unsignificant decrease in the mean arterial pressure (MAP) and heart rate (HR). Injection of bicuculline methiodide (BMI, 100 pmol/100 nl), a GABA(A) antagonist, caused a significant increase in the MAP (41.3+/-5.1 mmHg) as well as in the HR (33.2+/-5.6 beats/min). Injection of two doses (500 and 1000 pmol/100 nl) of phaclofen, a GABA(B) antagonist, produced no significant change in either MAP or HR. Administration (i.v.) of the muscarinic receptor blocker, homatropine methyl bromide had no effect on the magnitude of mean arterial pressure or heart rate responses to BMI. This suggests that the parasympathetic system is not involved in these responses. However, administration (i.v.) of the nicotinic receptor blocker, hexamethonium bromide had no effect on the magnitude of mean arterial pressure response but abolished heart rate response to BMI. This suggests that the sympathetic system is involved in the bradycardic effect of GABA. On the other hand, administration (i.v.) of a selective vasopressin V(1) receptor antagonist abolished the pressor effect of BMI, which indicates that the GABAergic system of the BST decreases the arterial pressure via tonic inhibition of vasopressin release. In summary, we demonstrated, for the first time, that GABA exerts its influence in the BST through the activation of GABA(A), but not GABA(B), receptors that, in turn, tonically inhibit vasopressin release and sympathetic outflow to the heart.