Chronic nitric oxide inhibition with <scp>l</scp>-NAME: effects  on autonomic control of the cardiovascular system

Scrogin, Karie E.; Hatton, Deborah D.; Chi, Yuling; Luft, Friedrich C.

doi:10.1152/ajpregu.1998.274.2.r367

Cited by 52 publications

(71 citation statements)

References 22 publications

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“…During L-NAME treatment, the CR protocol was continued, and the average dosage of L-NAME was estimated to be ϳ15 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 . This dose of L-NAME was chosen according to previous reports in which near-maximal inhibition of nitric oxide (NO) synthase (NOS) in the body was achieved (27,41). Four weeks later, isolated hearts were subjected to the same ischemia-reperfusion protocol (n ϭ 7 each).…”

Section: Methodsmentioning

confidence: 99%

Impact of 6-mo caloric restriction on myocardial ischemic tolerance: possible involvement of nitric oxide-dependent increase in nuclear Sirt1

Shinmura

Tamaki

Bolli

2008

American Journal of Physiology-Heart and Circulatory Physiology

115

114

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Ischemic tolerance decreases with aging, and the cardioprotective effect of ischemic preconditioning (IPC) is impaired in middle-aged animals. We have demonstrated that short-term caloric restriction (CR) improves myocardial ischemic tolerance in young and old animals via the activation of adiponectin-AMP-activated protein kinase (AMPK)-mediated signaling. However, it is unknown whether prolonged CR confers cardioprotection in a similar manner. Furthermore, little is known regarding the myocardial expression of silent information regulator 1 (Sirt1; which reportedly mediates various aspects of the CR response) with prolonged CR. Thus, 6-mo-old male Fischer-344 rats were randomly divided into ad libitum (AL) and CR groups. Six months later, isolated perfused hearts were subjected to 25 min of global ischemia followed by 120 min of reperfusion with or without IPC. CR improved the recovery of left ventricular function and reduced infarct size after ischemiareperfusion and restored the IPC effect. Serum adiponectin levels increased, but myocardial levels of total and phosphorylated AMPK did not change with prolonged CR. Total levels of Sirt1 did not change with CR; however, in the nuclear fraction, CR significantly increased Sirt1 and decreased acetyl-histone H3. Eleven rats from each group were given N-nitro-L-arginine methyl ester in their drinking water for 4 wk before death. In these hearts, chronic inhibition of nitric oxide synthase prevented the increase in nuclear Sirt1 content by CR and abrogated CR-induced cardioprotection. These results demonstrate that 1) prolonged CR improves myocardial ischemic tolerance and restores the IPC effect in middle-aged rats and 2) CR-induced cardioprotection is associated with a nitric oxidedependent increase in nuclear Sirt1 content. aging; myocardial ischemia; nutrition; preconditioning; reperfusion injury; silent information regulator 1

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Section: Methodsmentioning

confidence: 99%

Impact of 6-mo caloric restriction on myocardial ischemic tolerance: possible involvement of nitric oxide-dependent increase in nuclear Sirt1

Shinmura

Tamaki

Bolli

2008

American Journal of Physiology-Heart and Circulatory Physiology

115

114

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“…After 3 days acclimation, rats (250 to 270 g) were randomly divided into the nontreated groups (nϭ6) and the L-NAME-treated groups (nϭ7). L-NAME (Sigma) at a dose of 15 mg/kg per day 15 was given in drinking water for a 4-week experimental period.…”

Section: Methodsmentioning

confidence: 99%

Enhanced Superoxide Activity Modulates Renal Function in NO-Deficient Hypertensive Rats

Kopkan

Majid

2006

Hypertension

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Abstract-An enhancement of superoxide (O 2 Ϫ ) activity was shown to contribute to the development of hypertension induced by NO deficiency. To better understand the mechanistic role of O 2 Ϫ in this NO-deficient hypertension, we evaluated the renal responses to acute intraarterial administration of an O 2 Ϫ scavenger, tempol (50 g/min per 100 g of body weight) in anesthetized male Sprague-Dawley rats treated with NO synthase inhibitor nitro-L-arginine methyl ester (15 mg/kg per day in drinking water, nϭ7) for 4 weeks, which caused increases in mean arterial pressure (146Ϯ3 versus 124Ϯ2 mm Hg) compared with normotensive control rats (nϭ6). Hypertensive rats had higher renal vascular resistance (29Ϯ2 versus 20Ϯ1 mm Hg/mL per minute per gram), as well as lower renal blood flow (5.2Ϯ0.3 versus 6.3Ϯ0.2 mL/min per gram; cortical blood flow, 153Ϯ13 versus 191Ϯ8 perfusion units; medullary blood flow, 43Ϯ2 versus 51Ϯ3 perfusion units) and glomerular filtration rate (0.69Ϯ0.04 versus 0.90Ϯ0.05 mL/min per gram) without a significant difference in urinary sodium excretion (0.81Ϯ0.07 versus 0.86Ϯ0.12 mol/min per gram) compared with normotensive rats. Urinary 8-isoprostane excretion rate (6.8Ϯ0.7 versus 4.5Ϯ0.3 pg/min per gram) was higher in hypertensive than normotensive rats. Intraarterial infusion of tempol did not alter renal function in normotensive rats. However, tempol significantly decreased renal vascular resistance by 12Ϯ2% and urinary 8-isoprostane excretion rate by 24Ϯ4% and increased renal blood flow by 10Ϯ2%, cortical blood flow by 9Ϯ2%, medullary blood flow by 15Ϯ6%, glomerular filtration rate by 11Ϯ3%, and urinary sodium excretion by 19Ϯ5% in hypertensive rats. These data indicate that enhanced O 2 Ϫ activity modulates renal hemodynamics and excretory function during reduced NO production and, thus, contributes to the pathophysiology of the NO-deficient form of hypertension. A n imbalance between the production and the degradation of reactive oxygen species such as superoxide anion (O 2 Ϫ ) leads to the condition termed as "oxidative stress." It has been suggested that oxidative stress is involved in the pathophysiology of many forms of hypertension. 1-3 Treatment with an O 2 Ϫ scavenging agent, tempol (4-hydroxytetramethylpiperidime-1-oxyl), significantly reduces blood pressure in different hypertensive models 4,5 indicating that O 2 Ϫ plays a role in the development of hypertension. Recently, we also demonstrated that chronic treatment with tempol attenuated the development of hypertension and salt sensitivity in rats induced by chronic inhibition of NO synthase (NOS) in rats. 6 These results indicate that an enhanced O 2 Ϫ generation is involved in the pathogenesis of an NO-deficient form of hypertension. However, the exact mechanistic role of O 2 Ϫ in mediating the salt sensitivity and hypertension in the condition of NO deficiency has not yet been clearly defined.NO acts as an endogenous antioxidative agent by reacting with O 2 Ϫ generated in the living tissues, thus it provides a protective function aga...

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“…Measurements of urine output, food intake and water consumption were measured as described previously. 56 …”

Section: Metabolic Studymentioning

confidence: 99%

In vivo expression of GLP-1/IgG-Fc fusion protein enhances beta-cell mass and protects against streptozotocin-induced diabetes

et al. 2007

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Glucagon-like peptide 1 (GLP-1) and its analogue exendin-4 (Ex4) have displayed potent glucose homeostasis-modulating characteristics in type 2 diabetes (T2D). However, there are few reports of effectiveness in type 1 diabetes (T1D) therapy, where there is massive loss of b cells. We previously described a novel GLP-1 analogue consisting of the fusion of active GLP-1 and IgG heavy chain constant regions (GLP-1/IgG-Fc), and showed that in vivo expression of the protein, via electroporation-enhanced intramuscular plasmid-based gene transfer, normalized blood glucose levels in T2D-prone db/db mice. In the present study, GLP-1/IgG-Fc and Ex4/IgG-Fc were independently tested in multiple low-dose streptozotocin-induced T1D. Both GLP-1/ IgG-Fc and Ex4/IgG-Fc effectively reduced fed blood glucose levels in treated mice and ameliorated diabetes symptoms, where as control IgG-Fc had no effect. Treatment with GLP-1/IgG-Fc or Ex4/IgG-Fc improved glucose tolerance and increased circulating insulin and GLP-1 levels. It also significantly enhanced islet beta-cell mass, which is likely a major factor in the amelioration of diabetes. This suggests that GLP-1/IgG-Fc gene therapy may be applicable to diseases where there is either acute or chronic beta-cell injury.

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Chronic nitric oxide inhibition with l-NAME: effects on autonomic control of the cardiovascular system

Cited by 52 publications

References 22 publications

Impact of 6-mo caloric restriction on myocardial ischemic tolerance: possible involvement of nitric oxide-dependent increase in nuclear Sirt1

Impact of 6-mo caloric restriction on myocardial ischemic tolerance: possible involvement of nitric oxide-dependent increase in nuclear Sirt1

Enhanced Superoxide Activity Modulates Renal Function in NO-Deficient Hypertensive Rats

In vivo expression of GLP-1/IgG-Fc fusion protein enhances beta-cell mass and protects against streptozotocin-induced diabetes

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