Inhibition of nitric oxide synthase in the paraventricular nucleus prevents the hyperthermia-induced reduction of mesenteric blood flow in rats

2010 ◽  
Vol 299 (2) ◽  
pp. R596-R602 ◽  
Author(s):  
Feng Chen ◽  
Yuliang Wang ◽  
Joo Lee Cham ◽  
Emilio Badoer
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Core Temperature ◽  
Paraventricular Nucleus ◽  
Cardiovascular Responses ◽  
Body Core Temperature ◽  
Mesenteric Blood Flow ◽  
Body Core ◽  
Oxide Synthase

Increasing body core temperature reflexly decreases mesenteric blood flow (MBF), and the hypothalamic paraventricular nucleus (PVN) plays an essential role in this response. Nitric oxide (NO) is involved in temperature regulation and is concentrated within the PVN. The present study investigated whether NO in the PVN contributes to the cardiovascular responses elicited by hyperthermia. Anesthetized rats were microinjected bilaterally in the PVN (100 nl/side) with saline or NG-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor (100 or 200 nmol/100 nl) ( n = 5/group). Body core temperature was then elevated from 37°C to 39°C, and blood pressure (BP), heart rate (HR), MBF, and mesenteric vascular conductance (MVC) were monitored. In separate groups, l-NAME (200 nmol) ( n = 5) or saline ( n = 5) was microinjected in the PVN, but body core temperature was not elevated. In control rats, increasing body core temperature resulted in no marked change of BP but an increase in HR and significant decreases in MBF (15%) and MVC. Pretreatment with 100 nmol l-NAME did not affect the responses. In contrast, 200 nmol l-NAME prevented the normal reduction in MBF and MVC but did not significantly affect the BP and HR responses. In rats in which body core temperature was not increased, l-NAME reduced MBF by 19%. The present results suggest that endogenous NO in the PVN is important in mediating the reduction of MBF induced by hyperthermia. In the absence of hyperthermia, however, endogenous NO in the PVN may play a role in maintaining mesenteric vasodilation.

AT1 receptors in the paraventricular nucleus mediate the hyperthermia-induced reflex reduction of renal blood flow in rats

2011 ◽  
Vol 300 (2) ◽  
pp. R479-R485 ◽  
Author(s):  
Feng Chen ◽  
Fang Liu ◽  
Emilio Badoer
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Core Temperature ◽  
Paraventricular Nucleus ◽  
Cardiovascular Responses ◽  
Body Core Temperature ◽  
Ang Ii ◽  
At1 Receptors ◽  
Body Core ◽  
Renal Vascular

Increasing body core temperature reflexly decreases renal blood flow (RBF), and the hypothalamic paraventricular nucleus (PVN) plays an essential role in this response. ANG II in the brain is involved in the cardiovascular responses to hyperthermia, and ANG II receptors are highly concentrated in the PVN. The present study investigated whether ANG II in the PVN contributes to the cardiovascular responses elicited by hyperthermia. Rats anesthetized with urethane (1–1.4 g/kg iv) were microinjected bilaterally into the PVN (100 nl/side) with saline ( n = 5) or losartan (1 nmol/100 nl) ( n = 7), an AT1 receptor antagonist. Body core temperature was then elevated from 37°C to 41°C and blood pressure (BP), heart rate (HR), RBF, and renal vascular conductance (RVC) were monitored. In separate groups losartan ( n = 4) or saline ( n = 4) was microinjected into the PVN, but body core temperature was not elevated. Increasing body core temperature in control rats elicited significant decreases in RBF (−48 ± 5% from a resting level of 14.3 ± 1.4 ml/min) and MVC (−40 ± 4% from a resting level of 0.128 ± 0.013 ml/min·mmHg), and these effects were entirely prevented by pretreatment with losartan. In rats in which body core temperature was not altered, losartan microinjected into the PVN had no significant effects on these variables. The results suggest that endogenous ANG II acts on AT1 receptors in the PVN to mediate the reduction in RBF induced by hyperthermia.

Hypothalamic paraventricular nucleus is critical for renal vasoconstriction elicited by elevations in body temperature

2008 ◽  
Vol 294 (2) ◽  
pp. F309-F315 ◽  
Author(s):  
Joo Lee Cham ◽  
Emilio Badoer
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Renal Blood Flow ◽  
Core Temperature ◽  
Paraventricular Nucleus ◽  
Hypothalamic Paraventricular Nucleus ◽  
Body Core Temperature ◽  
Control Group ◽  
Body Core

Redistribution of blood from the viscera to the peripheral vasculature is the major cardiovascular response designed to restore thermoregulatory homeostasis after an elevation in body core temperature. In this study, we investigated the role of the hypothalamic paraventricular nucleus (PVN) in the reflex decrease in renal blood flow that is induced by hyperthermia, as this brain region is known to play a key role in renal function and may contribute to the central pathways underlying thermoregulatory responses. In anesthetized rats, blood pressure, heart rate, renal blood flow, and tail skin temperature were recorded in response to elevating body core temperature. In the control group, saline was microinjected bilaterally into the PVN; in the second group, muscimol (1 nmol in 100 nl per side) was microinjected to inhibit neuronal activity in the PVN; and in a third group, muscimol was microinjected outside the PVN. Compared with control, microinjection of muscimol into the PVN did not significantly affect the blood pressure or heart rate responses. However, the normal reflex reduction in renal blood flow observed in response to hyperthermia in the control group (∼70% from a resting level of 11.5 ml/min) was abolished by the microinjection of muscimol into the PVN (maximum reduction of 8% from a resting of 9.1 ml/min). This effect was specific to the PVN since microinjection of muscimol outside the PVN did not prevent the normal renal blood flow response. The data suggest that the PVN plays an essential role in the reflex decrease in renal blood flow elicited by hyperthermia.

Role of neuronal nitric oxide synthase in hypoxia-induced anapyrexia in rats

2000 ◽  
Vol 89 (3) ◽  
pp. 1131-1136 ◽  
Author(s):  
Alexandre A. Steiner ◽  
Evelin C. Carnio ◽  
Luiz G. S. Branco
Keyword(s):  
Nitric Oxide ◽  
Body Temperature ◽  
Nitric Oxide Synthase ◽  
Intraperitoneal Injection ◽  
Neuronal Nitric Oxide Synthase ◽  
Body Core Temperature ◽  
Body Core ◽  
Significant Attenuation ◽  
Oxide Synthase

Anapyrexia (a regulated decrease in body temperature) is a response to hypoxia that occurs in organisms ranging from protozoans to mammals, but very little is known about the mechanisms involved. Recently, it has been shown that the NO pathway plays a major role in hypoxia-induced anapyrexia. However, very little is known about which of the three different nitric oxide synthase isoforms (neuronal, endothelial, or inducible) is involved. The present study was designed to test the hypothesis that neuronal nitric oxide synthase (nNOS) plays a role in hypoxia-induced anapyrexia. Body core temperature (Tc) of awake, unrestrained rats was measured continuously using biotelemetry. Rats were submitted to hypoxia, 7-nitroindazole (7-NI; a selective nNOS inhibitor) injection, or both treatments together. Control animals received vehicle injections of the same volume. We observed a significant ( P < 0.05) reduction in Tc of ∼2.8°C after hypoxia (7% inspired O2), whereas intraperitoneal injection of 7-NI at 25 mg/kg caused no significant change in Tc. 7-NI at 30 mg/kg elicited a reduction in Tc and was abandoned in further experiments. When the two treatments were combined (25 mg/kg of 7-NI and 7% inspired O2), we observed a significant attenuation of hypoxia-induced anapyrexia. The data indicate that nNOS plays a role in hypoxia-induced anapyrexia.

The effects of selective nitric oxide synthase blocker on survival, mesenteric blood flow and multiple organ failure induced by zymosan1

2005 ◽  
Vol 124 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Pinar Tanriverdi ◽  
Bulent C. Yuksel ◽  
Kemal Rasa ◽  
Gulnur Guler ◽  
Alper B. Iskit ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Multiple Organ Failure ◽  
Organ Failure ◽  
Multiple Organ ◽  
Mesenteric Blood Flow ◽  
Oxide Synthase

Abstract 085: CHIP: E3 Ubiquitin Ligase Mediates Proteasomal Degradation of Neuronal Nitric Oxide Synthase in the Paraventricular Nucleus of Rats with Heart Failure

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Neeru M Sharma ◽  
Kenichi Katsurada ◽  
Xuefei Liu ◽  
Kaushik P Patel
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Nitric Oxide Synthase ◽  
Paraventricular Nucleus ◽  
Ubiquitin Ligase ◽  
Protein A ◽  
Neuronal Nitric Oxide Synthase ◽  
Proteasomal Degradation ◽  
Oxide Synthase

The exaggerated sympathetic drive is a characteristic of heart failure (HF) due to reduced neuronal nitric oxide synthase (nNOS) within the paraventricular nucleus (PVN). Previously we have shown that there were increased accumulation of nNOS-ubiquitin (nNOS-Ub) conjugates in the PVN of rats with HF (1.0±0.05 Sham vs. 1.29±0.06 HF) due to the increased levels of PIN (a protein inhibitor of nNOS, known to dissociate nNOS dimers into monomers) (0.76±0.10 Sham vs. 1.12±0.09 HF) and decreased levels of tetrahydrobiopterin (BH4): a cofactor required for stabilization of nNOS dimers (0.62±0.02 Sham vs. 0.44±0.03 HF). We also showed that there is blunted nitric oxide-mediated inhibition of sympathetic tone via the PVN in HF. Here we examined whether CHIP(C-terminus of Hsp70 -interacting protein), a chaperone-dependent E3 ubiquitin-protein isopeptide ligase known to ubiquitylate Hsp90-chaperoned proteins could act as an ubiquitin ligase for nNOS in the PVN. Immunofluorescence studies revealed colocalization of nNOS and CHIP in the PVN indicating their possible interaction. CHIP expression was increased by 50% in the PVN of rats with HF(0.96±0.08 Sham vs.1.44±0.10* HF). It is shown that Hsp90 protects nNOS from ubiquitination while Hsp70 promotes the ubiquitination and degradation. We observed significant upregulation of Hsp70 (0.49±0.03 Sham vs. 0.65±0.02* HF) with a trend toward the decrease in Hsp90 expression (0.90±0.07 Sham vs. 0.71±0.06 HF). The opposing effects of the two chaperones could account for the increased CHIP-mediated ubiquitination and degradation of dysfunctional nNOS monomers in the PVN of rats with HF. Furthermore, neuronal NG108-15 cell line transfected with the pCMV3-CHIP-GFP spark (CHIP overexpression plasmid) showed approximately 74% increase in CHIP with concomitant 49% decrease in nNOS expression. In vitro ubiquitination assay in NG108 cells transfected with pCMV-(HA-Ub) 8 and pCMV3-CHIP-GFP spark plasmid reveal increased HA-Ub-nNOS conjugates (1.13 ± 0.09 Scramble vs. 1.65 ± 0.12* CHIP plasmid). Taken together, our results identify CHIP as an E3 ligase for ubiquitination of dysfunctional nNOS and CHIP expression is augmented during HF leading to increased proteasomal degradation of nNOS in the PVN.

Nitric oxide synthase inhibition in healthy adults reduces regional and total cerebral macrovascular blood flow and microvascular perfusion

2021 ◽  
Author(s):  
Katrina J. Carter ◽  
Aaron T. Ward ◽  
J. Mikhail Kellawan ◽  
Marlowe W. Eldridge ◽  
Awni Al‐Subu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Healthy Adults ◽  
Microvascular Perfusion ◽  
Oxide Synthase

scholarly journals Rapid nontranscriptional activation of endothelial nitric oxide synthase mediates increased cerebral blood flow and stroke protection by corticosteroids

2003 ◽  
Vol 111 (5) ◽  
pp. 759-759
Author(s):  
Florian P. Limbourg ◽  
Zhihong Huang ◽  
Jean-Christophe Plumier ◽  
Tommaso Simoncini ◽  
Masayuki Fujioka ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Angiotensin II and nitric oxide in neural control of intrarenal blood flow

2005 ◽  
Vol 289 (3) ◽  
pp. R745-R754 ◽  
Author(s):  
Niwanthi W. Rajapakse ◽  
Amanda K. Sampson ◽  
Gabriela A. Eppel ◽  
Roger G. Evans
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Angiotensin Ii ◽  
Nitric Oxide Synthase ◽  
Neural Control ◽  
Renin Angiotensin System ◽  
Renal Medulla ◽  
Renal Nerve ◽  
Intrarenal Blood Flow ◽  
Oxide Synthase

We investigated the roles of the renin-angiotensin system and the significance of interactions between angiotensin II and nitric oxide, in responses of regional kidney perfusion to electrical renal nerve stimulation (RNS) in pentobarbital sodium-anesthetized rabbits. Under control conditions, RNS (0.5–8 Hz) reduced total renal blood flow (RBF; −89 ± 3% at 8 Hz) and cortical perfusion (CBF; −90 ± 2% at 8 Hz) more than medullary perfusion (MBF; −55 ± 5% at 8 Hz). Angiotensin II type 1 (AT1)-receptor antagonism (candesartan) blunted RNS-induced reductions in RBF ( P = 0.03), CBF ( P = 0.007), and MBF ( P = 0.04), particularly at 4 and 8 Hz. Nitric oxide synthase inhibition with NG-nitro-l-arginine (l-NNA) enhanced RBF ( P = 0.003), CBF ( P = 0.001), and MBF ( P = 0.03) responses to RNS, particularly at frequencies of 2 Hz and less. After candesartan pretreatment, l-NNA significantly enhanced RNS-induced reductions in RBF ( P = 0.04) and CBF ( P = 0.007) but not MBF ( P = 0.66). Renal arterial infusion of angiotensin II (5 ng·kg−1·min−1) selectively enhanced responses of MBF to RNS in l-NNA-pretreated but not in vehicle-pretreated rabbits. In contrast, greater doses of angiotensin II (5–15 ng·kg−1·min−1) blunted responses of MBF to RNS in rabbits with intact nitric oxide synthase. These results suggest that endogenous angiotensin II enhances, whereas nitric oxide blunts, neurally mediated vasoconstriction in the renal cortical and medullary circulations. In the renal medulla, but not the cortex, angiotensin II also appears to be able to blunt neurally mediated vasoconstriction.

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