Resistance training and caloric restriction prevent systolic blood pressure rise by improving the nitric oxide effect on smooth muscle and morphological changes in the aorta of ovariectomized rats

Although it has long been established that cerebrospinal fluid potassium concentration (CSF [K]) is very tightly regulated, it has been reported that rats made hypertensive by central infusions of aldosterone have significantly lower CSF [K] compared with normotensive controls. We investigated whether reduced CSF [K] is also present in another animal model of hypertension, the deoxycorticosterone acetate (DOCA)-salt rat, and we hypothesized that chronic intracerebroventricular (IVT) infusion of potassium with miniosmotic pumps might attenuate the rise in blood pressure observed in these rats. DOCA-salt rats without IVT infusions or with control CSF infusions (0.5 microliter/h of 2.9 mM K for 2 wk) had a significantly increased systolic blood pressure and a significantly lower CSF [K] compared with their respective sham groups. In contrast, DOCA-salt rats receiving IVT infusions with elevated [K] (10, 30, or 150 mM) had significantly lower blood pressures compared with those receiving control CSF. They also did not exhibit decreased CSF [K] compared with their respective sham groups. At 10 and 150 mM K, the blood pressure rise in DOCA-salt rats was not significantly different from shams. At 30 mM K, there was a slight, but significant, increase in blood pressure in the DOCA-salt rats compared with their shams, but this rise was still much less than in DOCA-salt rats infused with 2.9 mM K. Infusions with elevated [K] had no effect on blood pressure in the sham animals. These studies suggest that altered brain potassium homeostasis may play an important role in the development of DOCA-salt hypertension.

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Arterial blood pressure responses to graded transient arousal from sleep in normal humans

Journal of Applied Physiology ◽

10.1152/jappl.1993.74.3.1123 ◽

1993 ◽

Vol 74 (3) ◽

pp. 1123-1130 ◽

Cited By ~ 177

Author(s):

R. J. Davies ◽

P. J. Belt ◽

S. J. Roberts ◽

N. J. Ali ◽

J. R. Stradling

Keyword(s):

Blood Pressure ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Confidence Interval ◽

Rem Sleep ◽

High Frequency ◽

Pressure Rise ◽

Nrem Sleep ◽

Blood Pressure Rise ◽

Obstructive Sleep

During obstructive sleep apnea, transient arousal at the resumption of breathing is coincident with a substantial rise in blood pressure. To assess the hemodynamic effect of arousal alone, 149 transient stimuli were administered to five normal subjects. Two electroencephalograms (EEG), an electrooculogram, a submental electromyogram (EMG), and beat-to-beat blood pressure (Finapres, Ohmeda) were recorded in all subjects. Stimulus length was varied to produce a range of cortical EEG arousals that were graded as follows: 0, no increase in high-frequency EEG or EMG; 1, increased high-frequency EEG and/or EMG for < 10 s; 2, increased high-frequency EEG and/or EMG for > 10 s. Overall, compared with control values, average systolic pressure rose [nonrapid-eye-movement (NREM) sleep 10.0 +/- 7.69 (SD) mmHg; rapid-eye-movement (REM) sleep 6.0 +/- 6.73 mmHg] and average diastolic pressure rose (NREM sleep 6.1 +/- 4.43 mmHg; REM sleep 3.7 +/- 3.02 mmHg) over the 10 s following the stimulus (NREM sleep, P < 0.0001; REM sleep, P < 0.002). During NREM sleep, there was a trend toward larger blood pressure rises at larger grades of arousal (systolic: r = 0.22, 95% confidence interval 0.02–0.40; diastolic: r = 0.48, 95% confidence interval 0.31–0.62). The average blood pressure rise in response to the grade 2 arousals was approximately 75% of that during obstructive sleep apnea. Arousal stimuli that did not cause EEG arousal still produced a blood pressure rise (mean systolic rise 8.6 +/- 7.0 mmHg, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

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Dynamic cerebral autoregulatory response to blood pressure rise measured by near-infrared spectroscopy and intracranial pressure

Critical Care Medicine ◽

10.1097/00003246-200209000-00010 ◽

2002 ◽

Vol 30 (9) ◽

pp. 2014-2021 ◽

Cited By ~ 23

Author(s):

Bendicht P. Wagner ◽

Juerg Pfenninger

Keyword(s):

Blood Pressure ◽

Infrared Spectroscopy ◽

Intracranial Pressure ◽

Near Infrared Spectroscopy ◽

Near Infrared ◽

Pressure Rise ◽

Blood Pressure Rise

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Effects of maternal l-citrulline supplementation on renal function and blood pressure in offspring exposed to maternal caloric restriction: The impact of nitric oxide pathway

Nitric Oxide ◽

10.1016/j.niox.2010.03.005 ◽

2010 ◽

Vol 23 (1) ◽

pp. 34-41 ◽

Cited By ~ 60

Author(s):

You-Lin Tain ◽

Chih-Sung Hsieh ◽

I-Chun Lin ◽

Chih-Cheng Chen ◽

Jiunn-Ming Sheen ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Renal Function ◽

Caloric Restriction ◽

The Impact ◽

Nitric Oxide Pathway

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Effect of ascorbic acid supplementation on nitric oxide metabolites and systolic blood pressure in rats exposed to lead

Toxicology Letters ◽

10.1016/j.toxlet.2008.06.660 ◽

2008 ◽

Vol 180 ◽

pp. S36

Author(s):

Ali Khoshbaten ◽

Alireza Asgari ◽

Ali Norooz zadeh ◽

Mohammad Amani

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Ascorbic Acid ◽

Systolic Blood Pressure ◽

Acid Supplementation ◽

Nitric Oxide Metabolites ◽

Ascorbic Acid Supplementation

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Abstract 107: Cytochrome B5 Reductase 3 Sensitizes Soluble Guanylate Cyclase to Nitric Oxide in Vascular Smooth Muscle

Hypertension ◽

10.1161/hyp.66.suppl_1.107 ◽

2015 ◽

Vol 66 (suppl_1) ◽

Author(s):

Adam C Straub ◽

Anh T Nguyen ◽

Mizanur Rahaman ◽

Stephanie M Mutchler ◽

Megan Miller ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Guanylate Cyclase ◽

Soluble Guanylate Cyclase ◽

Cytochrome B5 ◽

Heme Iron ◽

Cytochrome B5 Reductase ◽

Arterial Blood

The inability nitric oxide (NO) to stimulate soluble guanylate cyclase (sGC) has been linked to numerous cardiovascular diseases (CVD) including hypertension. While several studies have defined the importance of sGC expression in the cardiovascular system, the basic mechanisms that regulate sGC activity remain incompletely understood. Here, we report for the first time that sGC heme iron redox state, which is essential for NO-induced sGC activation, is regulated by cytochrome B5 reductase 3 (CyB5R3). Genetic knockdown and pharmacological inhibition of CyB5R3 in primary rat vascular smooth muscle cells resulted in a 60% loss in cGMP production. Conversely, the sGC activator Bay 58-2667, which activates oxidized or heme free sGC, reversed these effects. Consistent with our cell culture work, purified protein studies demonstrate that CyB5R3 can directly reduce oxidized sGC heme iron and sensitize sGC to NO. To test the functional importance of Cyb5R3 activity, we cultured mouse thoracodorsal arteries with a pharmacological inhibitor of Cyb5R3 (ZINC 747) and performed vascular reactivity studies using pressure myography. Arteries treated with ZINC 747 showed decreased responsiveness the NO donor DETA-NONOate but increase sensitivity to Bay 58-2667. We then treated mice with 10mg/kg/day of ZINC 747 using osmotic mini pumps, which caused an increase in mean arterial blood pressure (107.5±3.4 vs 131±13.16) measured via radio telemetry. Lastly, translational studies reveal that the CyB5R3 T116S polymorphism with allele frequency 0.23 only in African Americans is unable to reduce sGC and correlates with increased blood pressure. Considering the defining role of sGC in NO signaling and the fact that the oxidation state of sGC may predict responses to NO therapies and new classes of sGC activator medications, we anticipate that these studies may significantly impact our understanding of biology, precision therapeutics (right drug for the right patient) and pharmacogenetics (T117S SNP based drug selection).

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