Tone In Man Research Articles

Commentaries on Viewpoint: Is the resting bradycardia in athletes the result of remodeling of the sinoatrial node rather than high vagal tone?

Commentaries on Viewpoint: Is the resting bradycardia in athletes the result of remodeling of the sinoatrial node rather than high vagal tone?

Endothelium in polycythemia secondary to obstructive lung disease

The object of this editorial is the report of Boyer et al in this issue of the Journal of Applied Physiology .It has two merits. One, endothelial function was studied in individuals with polycythemia secondary to obstructive lung disease, a condition not commonly addressed by cardiovascular investigators, although its presence is associated with a clearcut increase in cardiovascular risk .Two, the authors made use of virtually all techniques available in man to determine endothelial-dependent modulation of vascular tone, an unusual effort that differentiates this study from most other studies so far published. The results provide evidence that in polycythemic patients with obstructive lung disease the forearm vasoconstriction induced by L-NMMA administration was not reduced as compared to controls, while the brachial artery dilatation in response to post-ischemic hyperemia was increased.

Functional and immunocytochemical evidence for a role of ghrelin and des-octanoyl ghrelin in the regulation of vascular tone in man

Ghrelin is the recently identified endogenous ligand for the ghrelin receptor GHS-R1a and known to regulate growth hormone secretion and appetite. Ghrelin also is a potent vasodilator and improves cardiac performance after systemic administration. Generally, the octanoyl modification on Ser3 has been considered essential for biological activity. Recently however, cardiovascular actions of des-octanoyl ghrelin have been reported in rodents. Our aim was to investigate if ghrelin and ghrelin receptor protein are expressed within the human vasculature, to determine if des-octanoyl ghrelin, like ghrelin, is a vasodilator in human artery and to test the acute effect of ghrelin peptides on cardiac contractility. Distribution of ghrelin and ghrelin receptor was determined using standard immunocytochemistry and confocal microscopy. Ghrelin peptides were tested for vasodilator actions in human isolated arteries and their effect on cardiac contractility was investigated in human isolated paced atria. Immunoreactive ghrelin was detected in endothelial cells of human arteries and veins where it localized to intracellular vesicles but not to the Weibel-Palade bodies of the regulated pathway, suggesting constitutive ghrelin production. Specific antisera detected ghrelin receptor on vascular smooth muscle cells and cardiomyocytes. Ghrelin (pD2=8.60+/-0.1, Emax=55.8+/-8.9, mean+/-standard error of the mean) and des-octanoyl ghrelin (pD2=8.8+/-0.2, Emax=54.7+/-5.3) showed comparable (P>0.05) endothelium independent vasodilator potency and efficacy in reversing endothelin-1 induced constriction in human artery. Neither ghrelin nor des-octanoyl ghrelin had effects on contractile force in paced atria. We show widespread expression of ghrelin and its cognate receptor in the human cardiovascular system with functional evidence suggesting a role for both ghrelin and the more abundant endogenous form des-octanoyl ghrelin in the paracrine regulation of vascular tone in man.

Role of Toraco-Lumbo (T12l2)-Sacral (S2S4) Centers from Puberty to Aging

In the context of the structures concerning the neurophysiology, the cardiovascular system of it may be important to revalue the role of the Toraco-Lumbo (T12-L2 = sympathetic efferent section)-Sacral (S2-S4 = vagal afferent section) centers with integrative nitrergic system, the vascular peptides, in the field of an active microcirculation vasomotor mechanism from puberty to aging. These are the only centres of the spinal cords to have a prominent neurovasodilatory action through the beta-stimulation and alpha-blockade starting with Ach action, but also through the vagal termination S2-S4 where neurotransmitting vasodilator reflex NO-cgmp- dependent is produced. Nitric-oxyde participates also in regularizing the control on peripheral tone in man. The synthesis of NO occurs in cardiac-sympathetic and vagal ganglia. The same can be verified during puberty in the Toraco-Lumbo-Sacral ganglia, therefore the vasal vascular tone becomes dynamic. Different factors published produce a bettering of microcirculation vasomotility. Therefore one should consider the structural parallelism explaining the relationship between the Toraco-Lumbo and Sacral selective system, the sexual circuit with the NO-vasodilator system prevailing in the young-adult period, while in older ages the vasoconstrictor endothelins-1 system prevails.

The role of nitric oxide in the regulation of glomerular haemodynamics in humans.

According to experimental data, the afferent glomerular arteriole is particularly under control of nitric oxide (NO). By use of pharmacological manoeuvres, we examined whether this finding holds true in the human renal circulation in vivo. Seventy-seven volunteers (aged 50+/-9 years) with mild to moderate essential hypertension (n = 57) or arterial normotension (n = 20) were examined. Basal NO activity in the renal circulation was assessed by the change of renal plasma flow (RPF) through systemic infusion of the NO synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA; 4.25 mg/kg). Hypertensive patients were treated over 8 weeks with either the calcium-channel blocker amlodipine or the AT(1)-receptor blocker valsartan, primarily dilating the afferent and efferent arteriole, respectively. Subsequently, renal haemodynamics and NO activity in the renal circulation were determined again. L-NMMA reduced RPF in normotensive (by 57+/-70 ml/min/1.73 m(2); P<0.01) and hypertensive subjects (by 46+/-56 ml/min/1.73 m(2); P<0.001) with no significant difference between the two groups. The decrease of RPF through L-NMMA was closely related with the glomerular filtration rate (GFR; r = 0.39, P<0.001). Administration of amlodipine increased GFR by 7.1+/-12.1 ml/min/1.73 m(2); (P<0.01) and in parallel reduced the response of RPF to L-NMMA to 19+/-48 ml/min/1.73 m(2); (P<0.05). In contrast, valsartan maintained GFR and left the response of RPF to L-NMMA unchanged. NO plays an important role in the regulation of human glomerular haemodynamics, probably with a greater contribution to afferent than to efferent arteriolar tone in man.

Patients with the major and minor form of hyperekplexia differ with regards to disynaptic reciprocal inhibition between ankle flexor and extensor muscles.

The aim of the present study was to investigate the contribution of reciprocal inhibition to muscle tone by examining the transmission in the reciprocal inhibitory pathway in patients with a known defect in the glycine receptor. The study was performed in eight patients with hereditary hyperekplexia, six with the major form and two with the minor form of the disease. A mutation in the alpha1-subunit of the glycine receptor had been demonstrated in the patients with the major form, whereas no mutation was seen in the patients with the minor form. Disynaptic reciprocal inhibition, which is presumed to be mediated by glycine, was not seen in the patients with the major form of the disease, while it could be evoked in the patients with the minor form of the disease. Presynaptic inhibition, which is presumed to be mediated by GABA, was seen in both types of patients. It is concluded that the major form of hereditary hyperekplexia is associated with impaired transmission in glycinergic reciprocal inhibitory pathways. The findings demonstrate the importance of reciprocal inhibition for the muscle tone in man, and it is suggested that the impaired reciprocal inhibition seen in patients with a defect in the glycine receptor may contribute to the increased muscle stiffness that is observed in these patients.

Influence of sildenafil on fasting and postprandial gastric tone in man

Influence of sildenafil on fasting and postprandial gastric tone in man

Influence of sildenafil on fasting and postprandial gastric tone in man

Influence of sildenafil on fasting and postprandial gastric tone in man

Endogenous Bradykinin does not Contribute to the Maintenance of Basal Peripheral Arteriolar Tone in Man

Endogenous Bradykinin does not Contribute to the Maintenance of Basal Peripheral Arteriolar Tone in Man

Selective increase of the contractile response to endothelin-1 in subcutaneous arteries from patients with essential hypertension.

Endothelin-1 has been shown to contribute to basal vascular tone in man. Since endothelin-1 is a potent vasoconstrictor putatively involved in hypertension, we have compared the contractile responses of endothelin-1 and noradrenaline in relation to potassium chloride in subcutaneous resistance arteries from subjects with established essential hypertension with matched controls. Furthermore, with RT-PCR, the occurrence of mRNA for the ETA and ET(B) receptors was shown in the tunica media layer of subcutaneous arteries in controls and hypertensives. The maximum contractile response to endothelin-1 was significantly higher in the subcutaneous arteries of the hypertensives (by 88% with no change in potency) as compared to controls. The responses to noradrenaline, acetylcholine and potassium chloride did not differ between the groups. This selective increase in the contractile response to endothelin-1 might contribute to the development of essential hypertension.

Selective Increase of the Contractile Response to Endothelin-1 in Subcutaneous Arteries from Patients with Essential Hypertension

Endothelin-1 has been shown to contribute to basal vascular tone in man. Since endothelin-1 is a potent vasoconstrictor putatively involved in hypertension, we have compared the contractile responses of endothelin-1 and noradrenaline in relation to potassium chloride in subcutaneous resistance arteries from subjects with established essential hypertension with matched controls. Furthermore, with RT-PCR, the occurrence of mRNA for the ETA and ETB receptors was shown in the tunica media layer of subcutaneous arteries in controls and hypertensives. The maximum contractile response to endothelin-1 was significantly higher in the subcutaneous arteries of the hypertensives (by 88% with no change in potency) as compared to controls. The responses to noradrenaline, acetylcholine and potassium chloride did not differ between the groups. This selective increase in the contractile response to endothelin-1 might contribute to the development of essential hypertension.

A central γ-aminobutyric acid mechanism in cardiac vagal control in man revealed by studies with intravenous midazolam

1. Animal studies show that cardiac vagal tone can be modified by gamma-aminobutyric acid neurons acting at several sites in the central nervous system. The present study has attempted to determine whether similar control exists in humans by using midazolam, a benzodiazepine. Benzodiazepines exert their main actions on the central nervous system by interacting co-operatively at the gamma-aminobutyric acid receptor. 2. Twenty patients took part in the study before undergoing cardiac catheterization. After resting for 20 min in a semi-supine position on a couch, ECG, blood pressure and respiration were recorded for 5-min periods with either controlled (fixed) or free respiration. During this time a baroreceptor sensitivity test was conducted. 3. Doses of 1 mg and 5 mg of midazolam were administered intravenously. 4. Five-minute segments of data, before and after midazolam, were subjected to power spectral and time-domain analysis. 5. Midazolam caused a decrease in the high-frequency and an increase in the low-frequency components of the power spectral density plot, and in addition reduced the mean R-R interval and R-R variability expressed as the interquartile difference, and pNN50. There were no significant changes in the sensitivity of the baroreflex or in the systolic, diastolic and average blood pressures. 6. This decrease in variability of heart period, particularly at a controlled respiratory frequency, strongly suggests that cardiac vagal tone in man can be regulated by gamma-aminobutyric acid neurons.

Exercise and diving, two conflicting stimuli influencing cardiac vagal tone in man.

1. In order to increase our understanding of the central regulation of human cardiac vagal motoneurones we studied the interaction between two opposing influences on cardiac vagal tone, one related to diving and the other to exercise. 2. The heart rate response to cooling the face (0 degrees C, trigeminal cutaneous receptor stimulation, TGS) and to a brief isometric muscle contraction was studied in fourteen healthy young adults (8 males, 6 females) during controlled ventilation at supine rest. 3. Fluctuations in R-R interval were quantified by spectral analysis. In addition the absolute values of R-R intervals occurring in any one of ten arbitrary phases of a respiratory cycle were measured over thirty to sixty cycles to give a graph of the changes in R-R interval throughout a respiratory cycle. 4. TGS produced a significant decrease in heart rate (-21 +/- 2 beats min-1 in females, -19 +/- 2 beats min-1 in males; means +/- S.E.M.). In addition the autospectral plots of R-R interval variability showed that during TGS there was a significant increase both in the high frequency peak and in the low frequency peak in all subjects. These data suggested that in these experiments the bradycardia of TGS was due to an increase in cardiac vagal tone. 5. Voluntary isometric contractions at 40 and 60% of maximum (40% MVC, 60% MVC) were timed to occur early in expiration or early in inspiration. Analysis of the changes in R-R interval produced by these contractions was confined to the respiratory cycle in which they were initiated. The early onset of these changes was interpreted as showing a decrease in cardiac vagal tone. 6. The 40% MVC and 60% MVC increased heart rate significantly within one respiratory cycle with maximum effects having a mean of 9.5 +/- 3 and 11 +/- 3 beats min-1, respectively. When isometric muscle contraction was initiated during TGS the 60% MVC but not the 40% MVC was able to significantly decrease R-R interval and hence increase heart rate. 7. It is concluded that the TGS excitatory inputs and the muscle inhibitory inputs to cardiac vagal neurones do not interact by one input gating the other early in the pathway but more probably by a process of algebraic summation closer to the cardiac vagal neurone.

Elevated exhaled nitric oxide in patients with hepatopulmonary syndrome.

The hypoxaemia of hepatopulmonary syndrome, seen in severe chronic liver dysfunction, occurs as a result of precapillary pulmonary arterial dilatation and arteriovenous communications. These abnormalities contribute to the mismatch between ventilation and perfusion, and the right to left blood flow shunting. Nitric oxide (NO) is a powerful vasodilator concerned with the regulation of pulmonary vascular tone in man. Using a chemiluminescence analyser, we have measured endogenously produced NO in the exhaled air of three patients with the hepatopulmonary syndrome, six normoxaemic cirrhotic patients and six healthy volunteers. The subjects breathed NO-free air throughout the measurements. The molar rate of production of exhaled NO was raised almost threefold in the patients with hepatopulmonary syndrome compared with normal volunteers and with normoxaemic cirrhotic patients. Hypoxia per se, achieved in the normal volunteers by breathing a hypoxic gas mixture, reduced rather than increased the exhaled NO. One hepatopulmonary syndrome patient received an orthotopic liver transplant and achieved normoxaemia after 3 months. The exhaled NO also returned to normal. Increased pulmonary production of NO could contribute to the development of the hepatopulmonary syndrome.

Endothelins as Regulators of Vascular Tone in Man

1. The vascular pharmacology, physiological relevance and pathophysiological roles of the endothelium-derived vasoconstrictor peptide endothelin-1 have been unclear. These issues were investigated, in vivo in man, using infusion of drugs into the brachial artery or dorsal hand vein, with responses measured by forearm plethysmography and the hand vein displacement technique respectively. 2. Endothelin-1 is a potent and sustained constrictor of resistance and capacitance vessels in vivo in man, acting through both subtypes (ETA and ETB) of endothelin receptors. Endothelin-1 stimulates generation of vasodilator prostaglandins, but not of nitric oxide, that act to oppose its direct constrictor actions. Venoconstriction to endothelin-1 is blocked more effectively by K(+)-channel openers than by Ca(2+)-channel antagonists, suggesting a novel cellular mechanism of action for this peptide. 3. The forearm vasculature is able to convert the precursor big endothelin-1 to the mature peptide, endothelin-1, thus demonstrating the local presence of 'endothelin-converting enzyme' in man. Local inhibition of this enzyme, or blockade of ETA receptors, causes slow-onset forearm vasodilatation, suggesting that endogenously generated endothelin-1 contributes to basal resistance vessel tone in man. 4. Venoconstriction to endothelin-1 is selectively enhanced in patients with untreated essential hypertension. Endothelin-1 also potentiates sympathetically mediated vasoconstriction, but only in hypertensive subjects. 5. Endogenous generation of endothelin-1 plays a fundamental physiological role in the maintenance of basal vascular tone. Endothlin-converting enzyme inhibitors and endothelin receptor antagonists possess novel vasodilator properties and should represent a major therapeutic advance in cardiovascular disease.

Mechanism of hyperventilation-induced changes in colonic tone in man: [formula omitted], M. Camilleri, P.A. Low, R.B. Hanson, G.M. Thomforde, M.J. Ford, G.G. Klee, M.K. O'Connor. Mayo Clinic, Rochester, MN

Mechanism of hyperventilation-induced changes in colonic tone in man: [formula omitted], M. Camilleri, P.A. Low, R.B. Hanson, G.M. Thomforde, M.J. Ford, G.G. Klee, M.K. O'Connor. Mayo Clinic, Rochester, MN

Endothelins as Regulators of Vascular Tone in Man

Endothelins as Regulators of Vascular Tone in Man

28 A physiological role for endothelin in maintenance of yascular tone in man

28 A physiological role for endothelin in maintenance of yascular tone in man

A linear scale for measuring vagal tone in man.

1. Different levels of parasympathetic control of the heart were measured using ratios of the longest to the shortest intervals between R-waves in the ECGs (R-R) recorded during a deep breathing exercise in the supine position (respiratory sinus arrhythmia). The mean of absolute differences in consecutive R-R intervals was also measured in the supine position during quiet breathing (beat-to-beat variation), in six healthy volunteers, after cumulative doses of atropine (0.1-2.0 mg 70 kg-1, i.v.). 2. Full atropinization was observed at 2.0 mg 70 kg-1 where the respiratory sinus arrhythmia decreased by 97%, and the beat-to-beat variation dropped by 94%. There was no further drop in both indices at doses above 2.0 mg 70 kg-1. The different levels of parasympathetic control of the heart were directly proportional to the equivalent levels of respiratory sinus arrhythmia or beat-to-beat variation. 3. A universal linear vagal scale was calculated for use with these non-invasive indices to assess the levels of parasympathetic control of the heart. Zero in this scale would represent no activities in the cardiac vagus nerve. 4. It was concluded that vagal tone could be selectively measured in an intact person using these simplified and fast algorithms for quantifying respiratory sinus arrhythmia or beat-to-beat variation. A linear scale for measuring the vagal tone was possible. This linear scale was called the linear vagal scale (LVS).

What is the Effect of Arginine Vasopressin on Coronary and Systemic Vascular Tone in Man?

Conference Abstract| December 01 1989 What is the Effect of Arginine Vasopressin on Coronary and Systemic Vascular Tone in Man? J J Glazier; J J Glazier 1Boston University Medical Centre, Massachusetts, USA Introduced by Dr D. R. Hackett Search for other works by this author on: This Site PubMed Google Scholar H Gavras; H Gavras 1Boston University Medical Centre, Massachusetts, USA Introduced by Dr D. R. Hackett Search for other works by this author on: This Site PubMed Google Scholar R M Mills; R M Mills 1Boston University Medical Centre, Massachusetts, USA Introduced by Dr D. R. Hackett Search for other works by this author on: This Site PubMed Google Scholar M Bresnahan; M Bresnahan 1Boston University Medical Centre, Massachusetts, USA Introduced by Dr D. R. Hackett Search for other works by this author on: This Site PubMed Google Scholar T J Ryan; T J Ryan 1Boston University Medical Centre, Massachusetts, USA Introduced by Dr D. R. Hackett Search for other works by this author on: This Site PubMed Google Scholar D P Faxon D P Faxon 1Boston University Medical Centre, Massachusetts, USA Introduced by Dr D. R. Hackett Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1989) 77 (s21): 34P. https://doi.org/10.1042/cs077034Pa Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation J J Glazier, H Gavras, R M Mills, M Bresnahan, T J Ryan, D P Faxon; What is the Effect of Arginine Vasopressin on Coronary and Systemic Vascular Tone in Man?. Clin Sci (Lond) 1 December 1989; 77 (s21): 34P. doi: https://doi.org/10.1042/cs077034Pa Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1989 The Biochemical Society and the Medical Research Society1989 Article PDF first page preview Close Modal You do not currently have access to this content.