Abstract P196: Effect of Combined Oral Intake of Ginger Extract and Rice Vinegar on Blood Pressure with 2-kidney,1-clip Renovascular Hypertensive Rats

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Natsumi Saito ◽  
Yukiko Segawa ◽  
Saki Maruyama ◽  
Ayuna Yamaoka ◽  
Hiroko Hashimoto ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mrna Expression ◽  
Tap Water ◽  
Left Renal Artery ◽  
No Production ◽  
Sham Operation ◽  
Ginger Extract ◽  
Angiotensin Type 2 Receptor ◽  
Enos Mrna ◽  
Rice Vinegar

Objective: Ginger is widely used as traditional Asian herbal medicine. Ginger has the same pungent ingredient as chili and vanillyl. We showed that administration of capsaicin to renovascular hypertension (RH) model rats increased endothelial nitric oxide (NO) synthase (eNOS) mRNA expression and NO production, and suppressed blood pressure (BP). Traditionally in Japan, ginger is pickled and eaten. Ginger and vinegar each are supposed to have an effect of suppressing an increase in BP in RH rats. The aim of this study was to investigate the effect. Method: Male Sprague-Dawley rats (6wks) were treated with sham operation (SHAM) as controls or clipping the left renal artery (2K1C) as RH model. After surgery, the rats started receiving a control diet (C) or a diet with 0.08% (w/w) of Ginger Extract (GE) for 6 weeks, and a tap water (W) or a water with 4.5% (v/v) rice vinegar (V). The systolic BP (SBP) was measured by a tail-cuff method every week. At the end of the protocol, the mean arterial BP (MAP) was measured under anesthesia. Then, the aortas were removed for extracting mRNA. mRNA for angiotensin type 2 receptor (AT 2 ) and eNOS was evaluated by real-time RT-PCR. Results: Through the experiment period, SBP was significantly effects in time, model (SHAM vs 2K1C), diet (C vs GE) , timeхanimal ( P <0.001, each) and water (W vs V) ( P <0.05). At the end of the protocol, 2K1C-C+W was higher in SBP than SHAM-C+W (176 ± 6 vs 138 ± 1 mmHg, P <0.05). 2K1C-GE+W showed lower SBP (150 ± 2 mmHg) than -C+W ( P <0.05). SBP was not significantly different in 2K1C-GE+V (149 ± 4mmHg) from in -GE+W. The observations in MAP were similar to those in SBP. AT 2 R mRNA expression showed significant effects in model ( P <0.05) : the mRNA in 2K1C-C+W (0.9 ± 0.2) was significantly greater than in SHAM-C+W (0.4 ± 0.1) ( P <0.05). There were no significant differences among the 2K1Cs: -C+W, -C+V (0.9 ± 0.1), -GE+W (0.8 ± 0.1) and -GE+V (0.9 ± 0.2). eNOS mRNA expression showed significant effects only in diet (CTL vs GE, P <0.05), but not in water and any interactions. Conclusion: Continuous ingestion of GE and V may suppress BP increase in 2K1C, respectively. Simultaneous ingestion of GE and V showed no enhanced effects compared to GE or V solo ingestion in 2K1C. The roles of eNOS and AT 2 R in the mechanism did not become clear in this study.

Abstract P489: Effect of Continuous Intake of Hesperidin on Blood Pressure in 2-kidney, 1-clip Renovasucular Hypertensive Rats

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Ayuna Yamaoka ◽  
Yukiko Segawa ◽  
Saki Maruyama ◽  
Natsumi Saito ◽  
Hiroko Hashimoto ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mrna Expression ◽  
Control Diet ◽  
Left Renal Artery ◽  
Sham Operation ◽  
Hypertensive Rats ◽  
Fruit Peel ◽  
Arterial Blood ◽  
Significant Difference ◽  
Enos Mrna

Objective: Hesperidin (HES) is a flavonoid which is contained in citrus fruit peel. It has physiological effects on blood vessels such as strengthening capillary vessels. Thus, it is known to be one of the effective ingredients of herbal medicine. Some studies have shown that the intake of HES decreases blood pressure (BP) in spontaneously hypertensive rats. The antihypertensive effect of HES is suggested to be due to vasodilation by nitric oxide (NO). However, its mechanism has not been clarified in detail. In this study, we observed whether HES intake decreases BP in 2-kidney, 1-clip renovasucular hypertensive rats (2K1C) and evaluated endothelial NO synthase (eNOS) mRNA to investigate its role in the mechanism. Methods: Male Sprague-Dawley rats (6 weeks old) were treated with sham operation (SHAM) or clipping the left renal artery (2K1C). After surgery, the rats started receiving continuously a control diet (C) or a diet containing 0.1% (w/w) HES for 6 weeks. The systolic BP (SBP) was measured by a tail-cuff method every week. At the end of the protocol, mean arterial blood pressure (MAP) was measured in each rat under anesthesia. Then, the aortas were removed for extracting mRNA. eNOS mRNA expression was evaluated using real-time RT-PCR. Results: At the end of the protocol, SBP in 2K1C-C was significantly higher than in SHAM-C (170±6 vs 117±6 mmHg, p <0.001). On the other hand, 2K1C-HES was lower in SBP (141±4 mmHg) than 2K1C-C ( p <0.01). There were no significant differences between SHAM-HES (122±7 mmHg) and SHAM-C. MAP at the end of the protocol were similar to in SBP. ANOVA revealed mRNA expression of eNOS was significantly higher in 2K1C than in SHAM ( p <0.05), and showed no significant difference between C and HES, nor a significant interaction. Conclusion: Continuous intake of HES may suppress BP increase in 2K1C. The role of eNOS mRNA expression may not be involved in the mechanism.

Abstract P038: Dietary Capsaicin May Decrease Blood Pressure Through Enhancing NO With eNOS Activation in 2-Kidney, 1-Clip Hypertensive Rats

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Yukiko Segawa ◽  
Hiroko Hashimoto ◽  
Tomoko Osera ◽  
Nobutaka Kurihara
Keyword(s):  
Blood Pressure ◽  
Protein Expression ◽  
Mrna Expression ◽  
Dietary Therapy ◽  
Left Renal Artery ◽  
Sham Operation ◽  
Hypertensive Rats ◽  
Enos Mrna ◽  
Enos Protein Expression ◽  
Enos Protein

Objective: Capsaicin, a component of chili peppers, is reported to have beneficial effects on cardiovascular system through the vasodilative effects. We recently demonstrated the alleviation of blood pressure (BP) elevation by consuming a low concentration of capsaicin diet in 2-kidney, 1-clip (2K1C) hypertensive rats. Since the alleviation was diminished when 2K1C rats took NG-nitro-L-arginine methyl ester, a NO synthase (NOS) inhibitor, during the protocol, we hypothesized that NO has a key role in the effect of capsaicin in 2K1C rats. In this study, we observed eNOS mRNA expression and protein expressions of eNOS and phosphorylated eNOS in 2K1C rats fed a diet containing capsaicin. Methods: Six-week old male Sprague-Dawley rats were treated with sham operation (SHAM) or clipping the left renal artery (2K1C). One week after the surgery, each group of rats were further divided into 2 groups randomly, which received either a control diet (CTL) or a diet containing 0.006% capsaicin (CAP) for 6 weeks. The systolic BP was measured by a tail-cuff method once per week throughout the protocol. At the end of the protocol, rats were euthanized and the abdominal aortas were collected for extracting mRNA and protein. Then, the expression of eNOS mRNA and protein in aorta was evaluated in each group of rats by real time RT-PCR and Western blotting. Results: As shown in Table, capsaicin diet alleviated BP elevation in 2K1C rats. After the dietary protocol, eNOS mRNA expression in 2K1C-CAP was significantly higher than in 2K1C-CTL. Although there were no significant differences in eNOS protein expression among four groups, phosphorylated eNOS protein expression in 2K1C-CAP was marginally significantly higher than in 2K1C-CTL. The expression was also significantly higher in 2K1C rats than in SHAM. Discussion: The present data suggested that dietary capsaicin decreases BP through enhancing NO with activation of eNOS in 2K1C hypertensive rats. It may be a clue for developing a dietary therapy for prevention of hypertension.

Abstract 622: Role of Endothelial Nitric Oxide Synthase in a Capsaicin Diet-Induced Alleviation of Blood Pressure-Elevation in 2-Kidney, 1-Clip Hypertensive Rats

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Yukiko Segawa ◽  
Hiroko Hashimoto ◽  
Tomoko Osera ◽  
Nobutaka Kurihara
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Mrna Expression ◽  
Sensory Nerve ◽  
Left Renal Artery ◽  
Sham Operation ◽  
Hypertensive Rats ◽  
Blood Pressure Elevation ◽  
Significant Difference ◽  
Enos Mrna

Objective: Capsaicin directly acts on the sensory nerve ending and releases neuropeptides, which activate a vasodilator, nitric oxide (NO) and decrease blood pressure (BP). We demonstrated that BP elevation was alleviated by consuming a low concentration of capsaicin diet in 2-kidney, 1-clip (2K1C) hypertensive rats. We also observed that when 2K1C rats took the NO synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester, during the protocol, the effect of alleviating hypertension by dietary capsaicin was diminished. Thus, we hypothesized that NO is involved in the effect of capsaicin in 2K1C rats. In this study, to test the hypothesis, we observed endothelial NOS (eNOS) expression in 2K1C rats fed a diet containing capsaicin. Methods: Six-week old male Sprague-Dawley rats were treated with sham operation (SHAM) or clipping the left renal artery (2K1C). One week after the surgery, each group of rats were further divided into 2 groups randomly, which received either a control diet (CTL) or a diet containing 0.006% capsaicin (CAP) for 6 weeks. The systolic BP (SBP) was measured by a tail-cuff method once per week throughout the protocol. At the end of the protocol, MAP was measured in each rat under anesthesia. After euthanasia, the thoracic aortas were collected for extracting mRNA. Then, eNOS mRNA expression in aorta was evaluated in each group of rats by reverse transcriptase PCR. Results and Discussion: The present data of BP confirmed that capsaicin diet alleviates BP elevation in 2K1C rats. At six weeks after the surgery, SBP in 2K1C-CTL rats (183 ± 6 mmHg) was significantly higher than SHAM-CTL (124 ± 6 mmHg, p < 0.05), but SBP in 2K1C-CAP (140 ± 4 mmHg) was significantly lower than that in 2K1C-CTL. SHAM-CAP (129 ± 8 mmHg) did not show a significant difference in SBP with SHAM-CTL. MAP at the end of the protocol showed the same tendency as SBP. Moreover, eNOS mRNA expression was enhanced in 2K1C-CTL (0.39 ± 0.06) compared to SHAM-CTL (0.31 ± 0.04, p < 0.05). Although it was not enhanced in SHAM-CAP (0.30 ± 0.01) compared to SHAM-CTL, it was tended to be enhanced in 2K1C-CAP (0.43 ± 0.02) compared to 2K1C-CTL. These data suggested that dietary capsaicin decreased BP with elevation of eNOS mRNA expression in 2K1C rats, but did not change eNOS mRNA nor BP in SHAM normotensive rats.

Abstract P198: Combination of Undaria Pinnatifida Sporophyll and Vinegar Remarkably Decreases Blood Pressure in 2-kidney, 1-clip Renovascular Hypertensive Rats

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Saki Maruyama ◽  
Yukiko Segawa ◽  
Natsumi Saito ◽  
Ayuna Yamaoka ◽  
Hiroko Hashimoto ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mrna Expression ◽  
Undaria Pinnatifida ◽  
Tap Water ◽  
Control Diet ◽  
Interactive Effects ◽  
Left Renal Artery ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Hypertensive Rats

Objective: One of foods necessary to Japanese cuisine “Washoku” is algae, including Saccharina japonica (SJ) and Undaria pinnatifida (UP). The intake of SJ was observed to decrease blood pressure (BP) in spontaneously hypertensive rats in some studies, and in 2-kidney, 1-clip hypertensive (2K1C) rats in our studies. Furthermore, we observed the interactive effects of SJ and vinegar on BP in 2K1C rats (Kitamura S et al; Hypertension 2013, Maruyama S et al; Hypertension 2016). In the present study, we investigated the interactive effects of UP sporophyll (UPS) and vinegar, as well as the effect of UPS, on BP in 2K1C rats. We also evaluated angiotensin II type 1 receptor (AT1R) mRNA expression, in the mechanism. Methods: Male Sprague-Dawley rats (6 wks) were treated with sham operation (SHAM) or clipping the left renal artery (2K1C). After surgery, the rats started receiving a control diet (C) or a diet with 5.0% (w/w) UPS, and a tap water or a water containing 5.0% (v/v) rice vinegar (V) for 6 weeks. Systolic BP (SBP) was measured by a tail-cuff method every week. At the end of the protocol, mean arterial pressure (MAP) was measured in each rat under anesthesia. Then, the aortas were removed for extracting mRNA. AT1R mRNA expression was evaluated using real-time RT-PCR. Results: Through the experiment period, SBP was significantly higher in 2K1C-C than in SHAM-C ( P < 0.001). Neither 2K1C-V nor -UPS showed significant differences in SBP from 2K1C-C. However, 2K1C-UPS+V provided a significant reduction in SBP compared with 2K1C-C, -V, and -UPS ( P < 0.01). At the end of the protocol, 2K1C-C was higher in SBP than SHAM-C (166 ± 3 vs 137 ± 3 mmHg, P < 0.001). 2K1C-UPS+V (155 ± 4 mmHg) was tended to be lower than 2K1C-C, -V (162 ± 8 mmHg), and -UPS (164 ± 3 mmHg). Thus, BP was reduced only in 2K1C-UPS+V in 2K1C animals. The observations in MAP were similar to in the SBP. No significant differences in AT1R mRNA expression were observed among SHAM-C (1.3 ± 0.2), 2K1C-C (1.2 ± 0.3), -V (1.0 ± 0.2), -UPS (1.3 ± 0.2) and -UPS+V (1.0 ± 0.2). Conclusion: UPS and vinegar may decrease BP collaboratively in 2K1C rats. AT1R mRNA may not play an important role in the mechanism.

Abstract P165: Exploration of the Mechanism in Which Saccharina Japonica Alleviates an Increase in Blood Pressure in Renovasucular Hypertensive Rats

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Saki Maruyama ◽  
Yukiko Segawa ◽  
Hiroko Hashimoto ◽  
Tomoko Osea ◽  
Nobutaka Kurihara
Keyword(s):  
Blood Pressure ◽  
Mrna Expression ◽  
Control Diet ◽  
Renin Angiotensin System ◽  
Saccharina Japonica ◽  
Left Renal Artery ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Angiotensin Ii Receptor ◽  
Hypertensive Rats

Objective: Saccharina japonica (SJ), one of brown algae, is a common foodstuff in Japan and neighbor countries. Some studies have shown that the intake of SJ decreases blood pressure (BP) in spontaneously hypertensive rats. As well, we previously observed it in 2-kidney, 1-clip renovascular hypertensive (2K1C) rats. However, the mechanism is still unclear. One of possible components of SJ which play an important role in decreasing BP is alginate. Since alginate is richer in the roots than in the blades in SJ, in the present study, we compared the effects in alleviating BP of intake of SJ roots with that of SJ blades in 2K1C rats. We also evaluated angiotensin II receptor type 1 (AT1R) mRNA to investigate the role of renin-angiotensin system in the mechanism. Methods: Male Sprague-Dawley rats (6 wks) were treated with sham operation (SHAM) or clipping the left renal artery (2K1C). After surgery, the rats started receiving a control diet (C) or a diet containing 5.0% (w/w) SJ blades (B), or SJ roots (R) for 6 weeks. The systolic BP (SBP) was measured by a tail-cuff method every week. At the end of the protocol, mean arterial pressure (MAP) was measured in each rat under anesthesia. Then, the aortas were removed for extracting mRNA. AT1R-mRNA expression was evaluated using reverse transcriptase quantitative real-time PCR. Results: SBP was significantly higher in 2K1C-C than SHAM-C through the experiment period (p<0.001). SBP in 2K1C-B and -R was significantly lower than in 2K1C-C (p<0.001). 2K1C-B showed a significant reduction in SBP compared with in 2K1C-R (p<0.05). At the end of the protocol, MAP showed the similar trend to SBP. AT1R mRNA expression was higher in 2K1C than in SHAM, but there were no significant differences among 2K1C-C, -B and -R. Conclusion: Although alginate is richer in the roots than in the blades in SJ, the effects in alleviating BP was higher in the blades than in the roots. Thus, alginate may play no major role in the mechanism. AT1R may not play an important role, neither. Therefore, we need investigate other possible mechanisms.

Shear stress induces eNOS mRNA expression and improves endothelium-dependent dilation in senescent soleus muscle feed arteries

2005 ◽  
Vol 98 (3) ◽  
pp. 940-946 ◽  
Author(s):  
Christopher R. Woodman ◽  
Elmer M. Price ◽  
M. Harold Laughlin
Keyword(s):  
Shear Stress ◽  
Mrna Expression ◽  
Soleus Muscle ◽  
Low Flow ◽  
No Production ◽  
Fischer 344 ◽  
Enos Mrna ◽  
Series Of Experiments ◽  
Endothelial Nitric Oxide ◽  
Feed Arteries

We tested the hypothesis that increased intraluminal shear stress induces endothelial nitric oxide (NO) synthase (eNOS) mRNA expression and improves endothelium-dependent dilation in senescent soleus muscle feed arteries (SFA) by increasing NO production. SFA were isolated from young (4 mo) and old (24 mo) male Fischer 344 rats and cannulated with two resistance-matched glass micropipettes. SFA were exposed to no flow (NF), low flow (LF), intermediate flow (IF), or high flow (HF) for 4 h. Mean intraluminal shear stress ranged from 0 to 82 dyn/cm2. At the end of the 4-h treatment period, eNOS mRNA expression was assessed in each SFA. eNOS mRNA expression was significantly lower in old NF SFA than in young NF SFA. In old SFA, eNOS mRNA expression was induced by IF (+154%) and HF (+136%), resulting in a level of expression that was not different from that of young SFA. In a separate series of experiments, SFA were pretreated with NF or HF for 4 h, and endothelial function was assessed by examining vasodilator responses to ACh. ACh-induced dilation was less in old NF SFA than young NF SFA. Pretreatment with HF improved ACh-induced dilation in old SFA such that the response was similar to that of young SFA. In the presence of Nω-nitro-l-arginine to inhibit NOS, ACh-induced dilation was inhibited in old HF SFA such that the response was no longer greater than that of old NF SFA. These results indicate that increased intraluminal shear stress induces eNOS mRNA expression and improves endothelium-dependent dilation in senescent SFA by increasing NO production.

Endothelial nitric oxide production during in vitro simulation of external limb compression

2002 ◽  
Vol 282 (6) ◽  
pp. H2066-H2075 ◽  
Author(s):  
Guohao Dai ◽  
Olga Tsukurov ◽  
Michael Chen ◽  
Jonathan P. Gertler ◽  
Roger D. Kamm
Keyword(s):  
Nitric Oxide ◽  
Mrna Expression ◽  
Umbilical Vein ◽  
Control Group ◽  
No Production ◽  
Vein Thrombosis ◽  
Enos Mrna ◽  
Umbilical Vein Endothelial Cells ◽  
Endothelial Nitric Oxide

External pneumatic compression (EPC) is effective in preventing deep vein thrombosis (DVT) and is thought to alter endothelial thromboresistant properties. We investigated the effect of EPC on changes in nitric oxide (NO), a critical mediator in the regulation of vasomotor and platelet function. An in vitro cell culture system was developed to simulate flow and vessel collapse conditions under EPC. Human umbilical vein endothelial cells were cultured and subjected to tube compression (C), pulsatile flow (F), or a combination of the two (FC). NO production and endothelial nitric oxide synthase (eNOS) mRNA expression were measured. The data demonstrate that in the F and FC groups, there is a rapid release of NO followed by a sustained increase. NO production levels in the F and FC groups were almost identical, whereas the C group produced the same low amount of NO as the control group. Conditions F and FC also upregulate eNOS mRNA expression by a factor of 2.08 ± 0.25 and 2.11 ± 0.21, respectively, at 6 h. Experiments with different modes of EPC show that NO production and eNOS mRNA expression respond to different time cycles of compression. These results implicate enhanced NO release as a potentially important factor in the prevention of DVT.

scholarly journals L-sepiapterin restores SLE serum-induced markers of endothelial function in endothelial cells

2019 ◽  
Vol 6 (1) ◽  
pp. e000294 ◽  
Author(s):  
Joy N Jones Buie ◽  
Dorea Pleasant Jenkins ◽  
Robin Muise-Helmericks ◽  
Jim C Oates
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Mrna Expression ◽  
Neutrophil Migration ◽  
Basal Medium ◽  
Neutrophil Adhesion ◽  
No Production ◽  
Functional Changes ◽  
Enos Mrna ◽  
The Impact

ObjectiveSLE serves as an independent risk factor` for endothelial dysfunction (ED) not explained by Framingham risk factors. We sought to understand the development of SLE-induced ED on a cellular level in order to develop strategies aimed at reversing cellular abnormalities. This study assessed the impact of SLE patient serum on endothelial nitric oxide synthase (eNOS), nitric oxide (NO) production and functional changes in the cell.MethodsHuman umbilical vein endothelial cells (HUVECs) cultured in serum of either SLE (n=25) or healthy patients (n=14) or endothelial basal medium 2 (EBM-2) culture media supplemented with fetal bovine serum with or without L-sepiapterin were used for our studies. We applied the fluorescent probe DAF-FM diacetate for intracellular NO detection using flow cytometry. Total RNA isolates were analysed using reverse transcription PCR for eNOS mRNA expression. Oxygen consumption rate was determined using seahorse analysis. Neutrophil adhesion and migration were determined using a calcein AM microscopy assay.ResultsThe mRNA expression of eNOS was increased in SLE cultured HUVECs compared with healthy control (p<0.05). The SLE eNOS mRNA level correlated with SLE patient age (p=0.008); however, this trend was not observed with healthy patients. SLE serum reduced NO production in HUVECs compared with EBM-2 cultured cells (p<0.05). Co-treatment of endothelial cells with L-sepiapterin preserved HUVEC capacity to produce NO in SLE conditions (p<0.01). SLE serum enhanced neutrophil migration (p<0.01) but not neutrophil adhesion compared with healthy controls. The bioenergetic health index was not different.ConclusionsSLE likely causes disruption of endothelial cell eNOS function and NO modulated pathways.

Restoration of impaired endothelium-dependent coronary vasodilation in failing heart: role of eNOS phosphorylation and CGMP/cGK-I signaling

2007 ◽  
Vol 292 (6) ◽  
pp. H2782-H2790 ◽  
Author(s):  
Robert M. Gill ◽  
Julian C. Braz ◽  
Najia Jin ◽  
Gary J. Etgen ◽  
Weiqun Shen
Keyword(s):  
Heart Failure ◽  
Mrna Expression ◽  
Contractile Function ◽  
Left Ventricular ◽  
Smooth Muscle Relaxation ◽  
No Production ◽  
Partial Recovery ◽  
Vascular Relaxation ◽  
Cardiac Recovery ◽  
Enos Mrna

In congestive heart failure (CHF), coronary vascular relaxation is associated with endothelial dysfunction and nitric oxide (NO) deficiency. This study explored the reversibility of this process in hearts recovering from CHF and its related mechanisms. Dogs were chronically instrumented to measure cardiac function and coronary blood flow (CBF). Heart failure was induced by right ventricular pacing at 240 beats/min for 3–4 wk, and cardiac recovery (CR) was allowed by the termination of cardiac pacing for 3–4 wk after the development of CHF, in which left ventricular contractile function was restored by 80–90%. The endothelium-dependent CBF response to bradykinin and acetylcholine was depressed in CHF and fully restored in CR. Myocardial NOx (nitrate/nitrite), endothelial NO synthase (eNOS) mRNA expression, total protein, and phosphorylated eNOS decreased significantly in failing hearts. However, myocardial NOx recovered to 78% of control and phosphorylated eNOS was fully restored in CR, despite the fact that eNOS mRNA expression and protein levels remained lower than control. Furthermore, the endothelium-independent CBF response to nitroglycerin did not change in CHF; however, it increased by 75% in CR, in conjunction with a near threefold increase in the phosphorylation of vasodilation-stimulated phosphoprotein (VASP) at Ser239 in recovering hearts. Thus the complete restoration of endothelium-dependent coronary vascular relaxation during cardiac recovery from CHF was mediated by 1) a restoration of phosphorylated eNOS for partial recovery of the NO production and 2) an increase in cGMP/cGMP-dependent protein kinase-I pathway signaling activity for the enhancement of coronary vascular smooth muscle relaxation in response to NO.

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