Sildenafil acts on the central nervous system increasing sympathetic activity

2008 ◽  
Vol 104 (6) ◽  
pp. 1683-1689 ◽  
Author(s):  
Rubens Fazan ◽  
Domitila A. Huber ◽  
Carlos Alberto A. Silva ◽  
Valdo J. Dias da Silva ◽  
Maria Cristina O. Salgado ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Arterial Pressure ◽  
Sympathetic Activity ◽  
Baroreflex Sensitivity ◽  
Sympathetic Nerve Activity ◽  
Systolic Arterial Pressure ◽  
Nerve Activity ◽  
The Central Nervous System ◽  
Spontaneous Baroreflex

Sildenafil induces vasodilation and is used for treating erectile dysfunction. Although its influence on resting heart function appears to be minimal, recent studies suggest that sildenafil can increase sympathetic activity. We therefore tested whether sildenafil injected into the central nervous system alters the autonomic control of the cardiovascular system in conscious rats. The effect of sildenafil citrate injected into the lateral cerebral ventricle was evaluated in conscious rats by means of the recording of lumbar sympathetic nerve activity (LSNA), spectral analysis of systolic arterial pressure and heart rate variability, spontaneous baroreflex sensitivity, and baroreflex control of LSNA. Intracerebroventricular (ICV, 100 μg/5 μl) administration of sildenafil caused remarkable tachycardia without significant change in basal arterial pressure and was associated with a conspicuous increase (47 ± 14%) in LSNA. Spectral analysis demonstrated that systolic arterial pressure oscillations in the low frequency (LF) range were increased (from 6.3 ± 1.5 to 12.8 ± 3.8 mmHg2), whereas the high frequency (HF) range was not affected by ICV administration of sildenafil. Sildenafil increased pulse interval oscillations at LF and decreased them at HF. The LF-HF ratio increased from 0.04 ± 0.01 to 0.17 ± 0.06. Spontaneous baroreflex sensitivity measured by the sequence method and the baroreflex relationship between mean arterial pressure and LSNA were not affected by ICV administration of sildenafil. In conclusion, sildenafil elicited an increase in sympathetic nerve activity that is not baroreflex mediated, suggesting that this drug is able to elicit an autonomic imbalance of central origin. This finding may have implications for understanding the cardiovascular outcomes associated with the clinical use of this drug.

scholarly journals Amylin Acts in the Central Nervous System to Increase Sympathetic Nerve Activity

Endocrinology ◽  
2013 ◽  
Vol 154 (7) ◽  
pp. 2481-2488 ◽  
Author(s):  
Caroline Fernandes-Santos ◽  
Zhongming Zhang ◽  
Donald A. Morgan ◽  
Deng-Fu Guo ◽  
Andrew F. Russo ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Food Intake ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Peripheral Tissues ◽  
Brown Adipose ◽  
The Central Nervous System

Abstract The pancreatic hormone amylin acts in the central nervous system (CNS) to decrease food intake and body weight. We hypothesized that amylin action in the CNS promotes energy expenditure by increasing the activity of the sympathetic nervous system. In mice, ip administration of amylin significantly increased c-Fos immunoreactivity in hypothalamic and brainstem nuclei. In addition, mice treated with intracerebroventricular (icv) amylin (0.1 and 0.2 nmol) exhibited a dose-related decrease in food intake and body weight, measured 4 and 24 hours after treatment. The icv injection of amylin also increased body temperature in mice. Using direct multifiber sympathetic nerve recording, we found that icv amylin elicited a significant and dose-dependent increase in sympathetic nerve activity (SNA) subserving thermogenic brown adipose tissue (BAT). Of note, icv injection of amylin also evoked a significant and dose-related increase in lumbar and renal SNA. Importantly, icv pretreatment with the amylin receptor antagonist AC187 (20 nmol) abolished the BAT SNA response induced by icv amylin, indicating that the sympathetic effects of amylin are receptor-mediated. Conversely, icv amylin-induced BAT SNA response was enhanced in mice overexpressing the amylin receptor subunit, RAMP1 (receptor-activity modifying protein 1), in the CNS. Our data demonstrate that CNS action of amylin regulates sympathetic nerve outflow to peripheral tissues involved in energy balance and cardiovascular function.

scholarly journals Cardiovascular and Metabolic Crosstalk in the Brain: Leptin and Resistin

2021 ◽  
Vol 12 ◽  
Author(s):  
Emilio Badoer
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adipose Tissue ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Metabolic Complications ◽  
Brown Adipose ◽  
The Central Nervous System ◽  
The Brain

Leptin and resistin are cytokines whose plasma levels correlate with adiposity. Leptin is a hormone synthesised and released from adipocytes and can be transported into the brain. Resistin is produced in adipocytes in rodents and in macrophages in humans, particularly macrophages that have infiltrated adipose tissue. Both hormones can act within the brain to influence sympathetic nerve activity. Leptin appears to have a generalised sympatho-excitatory actions whilst resistin appears to increase sympathetic nerve activity affecting the cardiovascular system but inhibits sympathetic nerve activity to brown adipose tissue, which contrasts with leptin. Since both hormones can be elevated in conditions of metabolic dysfunction, interactions/crosstalk between these two hormones in the brain is a real possibility. This review describes the current knowledge regarding such crosstalk within the central nervous system. The evidence suggests that with respect to sympathetic nerve activity, crosstalk between leptin and resistin can elicit enhanced sympatho-excitatory responses to the kidneys. In contrast, with respect to food intake, resistin has weaker effects, but in regard to insulin secretion and thermogenesis, leptin and resistin have opposing actions. Thus, in conditions in which there is increased resistin and leptin levels, the result of crosstalk in the central nervous system could contribute to worse cardiovascular and metabolic complications.

scholarly journals Renin-Angiotensin System and Sympathetic Neurotransmitter Release in the Central Nervous System of Hypertension

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Kazushi Tsuda
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Sympathetic Nerve ◽  
Neurotransmitter Release ◽  
Sympathetic Nerve Activity ◽  
Renin Angiotensin System ◽  
Nerve Activity ◽  
Angiotensin System ◽  
The Central Nervous System ◽  
The Brain

Many Studies suggest that changes in sympathetic nerve activity in the central nervous system might have a crucial role in blood pressure control. The present paper discusses evidence in support of the concept that the brain renin-angiotensin system (RAS) might be linked to sympathetic nerve activity in hypertension. The amount of neurotransmitter release from sympathetic nerve endings can be regulated by presynaptic receptors located on nerve terminals. It has been proposed that alterations in sympathetic nervous activity in the central nervous system of hypertension might be partially due to abnormalities in presynaptic modulation of neurotransmitter release. Recent evidence indicates that all components of the RAS have been identified in the brain. It has been proposed that the brain RAS may actively participate in the modulation of neurotransmitter release and influence the central sympathetic outflow to the periphery. This paper summarizes the results of studies to evaluate the possible relationship between the brain RAS and sympathetic neurotransmitter release in the central nervous system of hypertension.

The Larval Eclosion Hormone Neurones in Manduca Sexta: Identification of the Brain-Proctodeal Neurosecretory System

1989 ◽  
Vol 147 (1) ◽  
pp. 457-470 ◽  
Author(s):  
JAMES W. TRUMAN ◽  
PHILIP F. COPENHAVER
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Manduca Sexta ◽  
Nerve Cord ◽  
Release Site ◽  
Neurosecretory System ◽  
Nerve Activity ◽  
Eclosion Hormone ◽  
The Central Nervous System ◽  
The Brain

Larval and pupal ecdyses of the moth Manduca sexta are triggered by eclosion hormone (EH) released from the ventral nervous system. The major store of EH activity in the latter resides in the proctodeal nerves that extend along the larval hindgut. At pupal ecdysis, the proctodeal nerves show a 90% depletion of stored activity, suggesting that they are the major release site for the circulating EH that causes ecdysis. Surgical experiments involving the transection of the nerve cord or removal of parts of the brain showed that the proctodeal nerve activity originates from the brain. Retrograde and anterograde cobalt fills and immunocytochemistry using antibodies against EH revealed two pairs of neurons that reside in the ventromedial region of the brain and whose axons travel ipsilaterally along the length of the central nervous system (CNS) and project into the proctodeal nerve, where they show varicose release sites. These neurons constitute a novel neuroendocrine pathway in insects which appears to be dedicated solely to the release of EH.

scholarly journals Acute effects of device-guided slow breathing on sympathetic nerve activity and baroreflex sensitivity in posttraumatic stress disorder

2018 ◽  
Vol 315 (1) ◽  
pp. H141-H149 ◽  
Author(s):  
Ida T. Fonkoue ◽  
Paul J. Marvar ◽  
Seth D. Norrholm ◽  
Melanie L. Kankam ◽  
Yunxiao Li ◽  
...  
Keyword(s):  
Posttraumatic Stress Disorder ◽  
Posttraumatic Stress ◽  
Sympathetic Activity ◽  
Baroreflex Sensitivity ◽  
Sympathetic Nerve Activity ◽  
Sham Group ◽  
Stress Disorder ◽  
Burst Frequency ◽  
Nerve Activity ◽  
Slow Breathing

Patients with posttraumatic stress disorder (PTSD) have elevated sympathetic nervous system reactivity and impaired sympathetic and cardiovagal baroreflex sensitivity (BRS). Device-guided slow breathing (DGB) has been shown to lower blood pressure (BP) and sympathetic activity in other patient populations. We hypothesized that DGB acutely lowers BP, heart rate (HR), and improves BRS in PTSD. In 23 prehypertensive veterans with PTSD, we measured continuous BP, ECG, and muscle sympathetic nerve activity (MSNA) at rest and during 15 min of DGB at 5 breaths/min ( n = 13) or identical sham device breathing at normal rates of 14 breaths/min (sham; n = 10). Sympathetic and cardiovagal BRS was quantified using pharmacological manipulation of BP via the modified Oxford technique at baseline and during the last 5 min of DGB or sham. There was a significant reduction in systolic BP (by −9 ± 2 mmHg, P < 0.001), diastolic BP (by −3 ± 1 mmHg, P = 0.019), mean arterial pressure (by −4 ± 1 mmHg, P = 0.002), and MSNA burst frequency (by −7.8 ± 2.1 bursts/min, P = 0.004) with DGB but no significant change in HR ( P > 0.05). Within the sham group, there was no significant change in diastolic BP, mean arterial pressure, HR, or MSNA burst frequency, but there was a small but significant decrease in systolic BP ( P = 0.034) and MSNA burst incidence ( P = 0.033). Sympathetic BRS increased significantly in the DGB group (−1.08 ± 0.25 to −2.29 ± 0.24 bursts·100 heart beats−1·mmHg−1, P = 0.014) but decreased in the sham group (−1.58 ± 0.34 to –0.82 ± 0.28 bursts·100 heart beats−1·mmHg−1, P = 0.025) (time × device, P = 0.001). There was no significant difference in the change in cardiovagal BRS between the groups (time × device, P = 0.496). DGB acutely lowers BP and MSNA and improves sympathetic but not cardiovagal BRS in prehypertensive veterans with PTSD. NEW & NOTEWORTHY Posttraumatic stress disorder is characterized by augmented sympathetic reactivity, impaired baroreflex sensitivity, and an increased risk for developing hypertension and cardiovascular disease. This is the first study to examine the potential beneficial effects of device-guided slow breathing on hemodynamics, sympathetic activity, and arterial baroreflex sensitivity in prehypertensive veterans with posttraumatic stress disorder.

Acute effects of electronic cigarettes on arterial pressure and peripheral sympathetic activity in young non-smokers

2020 ◽  
Author(s):  
Joshua Eric Gonzalez ◽  
William Harold Cooke
Keyword(s):  
Arterial Pressure ◽  
Health Risks ◽  
Sympathetic Activity ◽  
Sympathetic Nerve Activity ◽  
Electronic Cigarettes ◽  
Muscle Sympathetic Nerve Activity ◽  
Crossover Design ◽  
Acute Effects ◽  
Nerve Activity ◽  
Peripheral Sympathetic Activity

E-cigarettes like the JUUL are marketed as an alternative to smoking for those who want to decrease the health risks of tobacco. Tobacco cigarettes increase heart rate (HR) and arterial pressure (AP), while reducing muscle sympathetic nerve activity (MSNA) through sympathetic baroreflex inhibition. The acute effects of e-cigarettes on AP and MSNA have not been reported: our purpose was to clarify this issue. Using a randomized crossover design, participants inhaled on a JUUL containing nicotine (59 mg/ml) and a similar placebo e-cigarette (0 mg/ml). Experiments were separated by ~1 month. We recorded baseline ECG, AP (n=15), and MSNA (n=10). Subjects rested for 10 min, (BASE) and then inhaled once every 30 s on an e-cigarette that contained nicotine or placebo (VAPE) for 10 min followed by a 10-min recovery (REC). Data were expressed as Δmeans±SE from BASE. HR increased in the nicotine condition during VAPE and returned to BASE values in REC (5.0±1.3 nicotine vs 0.1±0.8 b/min placebo, during VAPE P<.01). AP increased in the nicotine condition during VAPE and remained elevated during REC. (6.5±1.6 nicotine vs 2.6±1 mmHg placebo, during VAPE and 4.6.0±1.7 nicotine vs 1.4±1.4 mmHg placebo during REC; p<.05). MSNA decreased from BASE to VAPE and did not restore during REC (-7.1±1.6 nicotine vs 2.6±2 bursts/min placebo during VAPE and -5.8±1.7 nicotine vs 0.5±1.4 placebo during REC; p<.05). Our results show that acute e-cigarette usage increases mean arterial pressure leading to a baroreflex mediated inhibition of MSNA.

Hormonal-sympathetic interactions in long-term regulation of arterial pressure: an hypothesis

1995 ◽  
Vol 268 (6) ◽  
pp. R1343-R1358 ◽  
Author(s):  
V. L. Brooks ◽  
J. W. Osborn
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Arterial Pressure ◽  
Plasma Concentrations ◽  
Circumventricular Organs ◽  
Feedback Signal ◽  
Salt Loading ◽  
Alternate Model ◽  
The Central Nervous System

The importance of the sympathetic nervous system in short-term regulation of arterial pressure is well accepted. However, the question of whether neural systems participate in long-term control of pressure has been debated for decades and remains unresolved. The principal argument against such a control system is that arterial baroreceptors adapt to sustained changes in arterial pressure. In addition, denervation of baroreceptors has minimal to no effect on basal levels of arterial pressure chronically. This argument assumes, however, that baroreceptors provide the primary chronic feedback signal to the central nervous system. An alternate model is proposed in which circulating hormones, primarily arginine vasopressin and angiotensin II, provide a long-term afferent signal to the central nervous system via binding to specific receptors in central sites lacking a blood-brain barrier (circumventricular organs). Studies suggest that the release of the hormones and the sympathetic response to alterations in their plasma concentrations are nonadaptive but may be gated by baroreceptor input. Evidence that this "hormonal-sympathetic reflex" model may explain the long-term alterations in sympathetic activity in response to chronic salt depletion and salt loading as well as congestive heart failure is presented. Finally, the role of an impaired hormonal sympathetic reflex in hypertension, specifically salt-dependent hypertension, is discussed.

Is there a central nervous system component to acute baroreflex resetting in rats?

1992 ◽  
Vol 262 (2) ◽  
pp. H503-H510 ◽  
Author(s):  
C. M. Heesch ◽  
K. W. Barron
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nerve Stimulation ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
System Component ◽  
Nerve Activity ◽  
Linear Portion ◽  
Aortic Nerve ◽  
Maximum Inhibition

This study was designed to evaluate a possible central nervous system (CNS) component to acute baroreflex resetting. In nine arterial baroreceptor-denervated, chloralose-urethan-anesthetized rats, a control (C) aortic nerve stimulation curve (3-5 V, 1 ms, 0-64 Hz) was obtained. Next, a constant "baroreceptor" input was delivered to the CNS (left aortic nerve stimulation, 10 min, 10.2 +/- 1.5 Hz). Within the first 13 s of aortic nerve stimulation, maximum inhibition of lumbar sympathetic nerve activity (LSNA) was 60 +/- 7.8% of baseline and at 1 min it increased to 68 +/- 5.6% of baseline. At the end of the 10-min aortic nerve stimulation, LSNA was not different from the response at 1 min (68 +/- 5.6% = 74 +/- 4.1%). Immediately after the constant stimulation (within 30 s), a test or reset (RS) curve was obtained (0-64 Hz). A recovery (RC) curve was obtained 10-20 min later. The slope of the linear portion of the curve and the stimulation frequency that produced 50% maximum inhibition (ES50) were compared among the three baroreflex curves (C, RS, RC,) and no significant differences were found. Thus, although a CNS component to baroreflex adaptation was evident during the first minute of aortic nerve stimulation, a longer term acute resetting of the baroreflex curve did not occur.

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