Assessment of microvascular endothelial function in human skin

2001 ◽  
Vol 101 (6) ◽  
pp. 567-572 ◽  
Author(s):  
David J. NEWTON ◽  
Faisel KHAN ◽  
Jill J.F. BELCH
Keyword(s):  
Blood Flow ◽  
Substance P ◽  
Endothelial Function ◽  
Animal Studies ◽  
Doppler Imaging ◽  
Microvascular Blood Flow ◽  
Coefficients Of Variation ◽  
Forearm Skin ◽  
Invasive Techniques ◽  
Dose Dependent

Endothelial dysfunction is an important factor in many cardiovascular diseases, and is commonly associated with impaired endothelium-mediated vasodilatation. Information about the mechanisms behind this dysfunction has come largely from animal studies or, in humans, through invasive techniques that are not specific to one vascular bed. We have developed protocols to assess endothelial function non-invasively in the cutaneous microcirculation by measuring blood flow responses to four receptor-specific vasoactive compounds. Cumulative doses of acetylcholine, methacholine, bradykinin and substance P were administered iontophoretically to the forearm skin of healthy volunteers on two to three occasions. Dose-dependent increases in skin microvascular blood flow in response to these drugs were measured with laser Doppler imaging. Vascular responses to acetylcholine and methacholine were reasonably consistent, with coefficients of variation of approx. 17%. The coefficients of variation for bradykinin and substance P were much poorer, as high as 70% for some doses. This might partly be a consequence of the more unpredictable effects of histamine release in the vasoactive behaviour of these two agonists. Although it might be advantageous to find other agonists with which to test the function of different receptor pathways, we have shown that just acetylcholine and methacholine can currently be used with iontophoresis to allow sensitive and reproducible assessment of endothelial function.

Effect of neuropeptides released from sensory nerves on blood flow in the rat airway microcirculation

1992 ◽  
Vol 72 (4) ◽  
pp. 1563-1570 ◽  
Author(s):  
G. Piedimonte ◽  
J. I. Hoffman ◽  
W. K. Husseini ◽  
W. L. Hiser ◽  
J. A. Nadel
Keyword(s):  
Blood Flow ◽  
Substance P ◽  
Regional Blood Flow ◽  
Reference Sample ◽  
Left Ventricular ◽  
Sensory Nerves ◽  
Microvascular Blood Flow ◽  
Systemic Injection ◽  
Airway Mucosa ◽  
Stimulation Of

Stimulation of sensory nerves in the airway mucosa causes local release of the neuropeptides substance P and calcitonin gene-related peptide (CGRP). In this study we used a modification of the reference-sample microsphere technique to measure changes in regional blood flow and cardiac output distribution produced in the rat by substance P, CGRP, and capsaicin (a drug that releases endogenous neuropeptides from sensory nerves). Three sets of microspheres labeled with different radionuclides were injected into the left ventricle of anesthetized F344 rats before, immediately after, and 5 min after left ventricular injections of capsaicin, substance P, or CGRP. The reference blood sample was withdrawn from the abdominal aorta and was simultaneously replaced with 0.9% NaCl at 37 degrees C. We found that stimulation of sensory nerves with a low dose of capsaicin causes a large and selective increase in microvascular blood flow in the extrapulmonary airways. The effect of capsaicin is mimicked by systemic injection of substance P but not by CGRP, suggesting that substance P is the main agent of neurogenic vasodilation in rat airways.

Role of Nitric Oxide towards Vasodilator Effects of Substance P and ATP in Human Forearm Vessels

1997 ◽  
Vol 92 (2) ◽  
pp. 123-131 ◽  
Author(s):  
Masanari Shiramoto ◽  
Tsutomu Imaizumi ◽  
Yoshitaka Hirooka ◽  
Toyonari Endo ◽  
Takashi Namba ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Substance P ◽  
Sodium Nitroprusside ◽  
Forearm Blood Flow ◽  
Dependent Manner ◽  
Human Forearm ◽  
Before And After ◽  
Dose Dependent

1. It has been shown in animals that substance P as well as acetylcholine releases endothelium-derived nitric oxide and evokes vasodilatation and that ATP-induced vasodilatation is partially mediated by nitric oxide. The aim of this study was to examine whether vasodilator effects of substance P and ATP are mediated by nitric oxide in humans. 2. In healthy volunteers (n = 35), we measured forearm blood flow by a strain-gauge plethysmograph while infusing graded doses of acetylcholine, substance P, ATP or sodium nitroprusside into the brachial artery before and after infusion of NG-monomethyl-l-arginine (4 or 8 μmol/min for 5 min). In addition, we measured forearm blood flow while infusing substance P before and during infusion of l-arginine (10 mg/min, simultaneously), or before and 1 h after oral administration of indomethacin (75 mg). 3. Acetylcholine, substance P, ATP or sodium nitroprusside increased forearm blood flow in a dose-dependent manner. NG-Monomethyl-l-arginine decreased basal forearm blood flow and inhibited acetylcholine-induced vasodilatation but did not affect substance P-, ATP-, or sodium nitroprusside-induced vasodilatation. Neither supplementation of l-arginine nor pretreatment with indomethacin affected substance P-induced vasodilatation. 4. Our results suggest that, in the human forearm vessels, substance P-induced vasodilatation may not be mediated by either nitric oxide or prostaglandins and that ATP-induced vasodilatation may also not be mediated by nitric oxide.

Arginine vasopressin reduces intestinal oxygen supply and mucosal tissue oxygen tension

2005 ◽  
Vol 289 (1) ◽  
pp. H168-H173 ◽  
Author(s):  
H. Knotzer ◽  
W. Pajk ◽  
S. Maier ◽  
R. Ladurner ◽  
A. Kleinsasser ◽  
...  
Keyword(s):  
Blood Flow ◽  
Oxygen Saturation ◽  
Arginine Vasopressin ◽  
Oxygen Supply ◽  
Microvascular Blood Flow ◽  
Jejunal Mucosa ◽  
Dependent Manner ◽  
Mucosal Tissue ◽  
Systemic Oxygen ◽  
Dose Dependent

We investigated intestinal oxygen supply and mucosal tissue Po2during administration of increasing dosages of continuously infused arginine vasopressin (AVP) in an autoperfused, innervated jejunal segments in anesthetized pigs. Mucosal tissue Po2was measured by employing two Clark-type surface oxygen electrodes. Oxygen saturation of jejunal microvascular hemoglobin was determined by tissue reflectance spectrophotometry. Microvascular blood flow was assessed by laser-Doppler velocimetry. Systemic hemodynamic variables, mesenteric venous and systemic acid-base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline and at 20-min intervals during incremental AVP infusion ( n = 8; 0.007, 0.014, 0.029, 0.057, 0.114, and 0.229 IU·kg−1·h−1, respectively) or infusion of saline ( n = 8). AVP infusion led to a significant ( P < .05), dose-dependent decrease in cardiac index (from 121 ± 31 to 77 ± 27 ml·kg−1·min−1at 0.229 IU·kg−1·h−1) and systemic oxygen delivery (from 14 ± 3 to 9 ± 3 ml·kg−1·min−1at 0.229 IU·kg−1·h−1) concomitant with an increase in systemic oxygen extraction ratio (from 31 ± 4 to 48 ± 10%). AVP decreased microvascular blood flow (from 133 ± 47 to 82 ± 35 perfusion units at 0.114 IU·kg−1·h−1), mucosal tissue Po2(from 26 ± 7 to 7 ± 2 mmHg at 0.229 IU·kg−1·h−1), and microvascular hemoglobin oxygen saturation (from 51 ± 9 to 26 ± 12% at 0.229 IU·kg−1·h−1) without a significant increase in mesenteric venous lactate concentration (2.3 ± 0.8 vs. 3.4 ± 0.7 mmol/l). We conclude that continuously infused AVP decreases intestinal oxygen supply and mucosal tissue Po2due to a reduction in microvascular blood flow and due to the special vascular supply in the jejunal mucosa in a dose-dependent manner in pigs.

Role of Substance P in the Vascular Response of Nasal Mucosa in Nasal Allergy

1996 ◽  
Vol 105 (8) ◽  
pp. 648-653 ◽  
Author(s):  
Akiyoshi Konno ◽  
Toyoyuki Hanazawa ◽  
Tsutomu Numata ◽  
Hiroshi Nagata ◽  
Nobuhisa Terada ◽  
...  
Keyword(s):  
Blood Flow ◽  
Substance P ◽  
Sensory Stimulation ◽  
Nasal Allergy ◽  
Vascular Response ◽  
Nasal Challenge ◽  
C Fiber ◽  
Capacitance Vessels ◽  
Dose Dependent

The effects of topically administered substance P (SP) on nasal blood flow and nasal airway resistance (NAR) were evaluated in 11 subjects with perennial nasal allergy. The change in NAR induced by SP was compared with those induced by nasal challenge with histamine, leukotriene EM (LTD4), and antigen. In doses ⩾ 16 nmol, SP caused a significant increase of nasal blood flow within 5 minutes that lasted for less than 20 minutes. In doses ⩾16 nmol, SP caused a dose-dependent, short-lasting, significant increase in NAR. The magnitude of the increase in NAR was LTD4 > SP > histamine when compared on a molar basis. Our results may suggest that SP released from C fiber terminals is partially involved in an early nasal vascular response after antigen challenge by acting on adjacent vascular smooth muscle to cause a transient vasodilatation of both resistance and capacitance vessels only while sensory stimulation persists in subjects with nasal allergy.

Influence of vehicle resistance on transdermal iontophoretic delivery of acetylcholine and sodium nitroprusside in humans

2004 ◽  
Vol 97 (3) ◽  
pp. 883-887 ◽  
Author(s):  
Faisel Khan ◽  
David J. Newton ◽  
Emily C. Smyth ◽  
Jill J. F. Belch
Keyword(s):  
Blood Flow ◽  
Sodium Nitroprusside ◽  
Electrical Resistance ◽  
Deionized Water ◽  
Microvascular Function ◽  
Doppler Imaging ◽  
Laser Doppler Imaging ◽  
Valuable Method ◽  
Forearm Skin ◽  
Iontophoretic Delivery

Iontophoresis is a valuable method of noninvasive drug delivery for assessment of skin microvascular function, but it is important to consider and minimize its potential nonspecific electrical effects on blood flow. The use of sodium chloride (NaCl) instead of water as the iontophoresis vehicle has been reported to reduce these effects because it has a lower electrical resistance. However, this argument may not be valid when an agonist is added to the vehicle because its resistance will be changed. The aim of our study was to determine whether there is a difference in resistance between water and NaCl when used as vehicles for iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Four cumulative doses of each drug, dissolved in either water or NaCl, were delivered via iontophoresis to the forearm skin of 14 healthy volunteers. We measured the resulting blood flow responses by using laser-Doppler imaging and the voltage across the electrodes for each delivery as an index of resistance. For ACh and SNP, there were no significant differences between the voltages measured when either water or NaCl was used as the vehicle. However, the blood flow responses to both agonists were significantly lower with NaCl (ACh: 25% lower, P < 0.001; SNP: 15% lower, P = 0.019). The use of NaCl is therefore unlikely to decrease any nonspecific electrical effects, and it may in fact reduce the effective dose of drug delivered. Deionized water is a better iontophoresis vehicle for the assessment of microvascular function in skin when using ACh and SNP.

Intracoronary endothelin receptor blockade improves endothelial function in patients with coronary artery disease

2008 ◽  
Vol 86 (11) ◽  
pp. 745-751 ◽  
Author(s):  
Felix Böhm ◽  
Jens Jensen ◽  
Bertil Svane ◽  
Magnus Settergren ◽  
John Pernow
Keyword(s):  
Coronary Artery Disease ◽  
Blood Flow ◽  
Coronary Artery ◽  
Substance P ◽  
Endothelial Function ◽  
Receptor Antagonist ◽  
Receptor Blockade ◽  
Flow Reserve ◽  
Artery Disease ◽  
Increased Blood Flow

Endothelin (ET)-1 receptor blockade improves endothelial function in the forearm of patients with atherosclerosis. The aim was to investigate whether intracoronary ET receptor blockade improves coronary endothelial function and increases blood flow in patients with coronary artery disease. Ten patients received a 60-minute infusion of either the selective ETA receptor antagonist BQ123 (40 nmol/min, n = 6) or BQ123 + the ETB receptor antagonist BQ788 (40 nmol/min, n = 4). In all patients, substance P, an endothelium-dependent vasodilator, did not increase baseline coronary flow reserve with thermodilution (CFRThermo) (0.71 ± 0.14 s during NaCl versus 0.59 ± 0.14 s during substance P) or baseline quantitative coronary angiography (QCA) (2.74 ± 0.16 mm versus 2.83 ± 0.20 mm). After ET receptor blockade, however, the response to substance P was significantly improved as determined both by CFRThermo (0.62 ± 0.14 s during NaCl versus 0.48 ± 0.10 s during substance P, p < 0.05) and by QCA (2.70 ± 0.18 mm versus 2.85 ± 0.19 mm, p < 0.05). In addition, ET blockade increased blood flow in all patients by 16% ± 10% (n = 10, p < 0.05) and in the BQ123 group by 22% ± 16% (n = 6, p < 0.05). Furthermore, ETA blockade increased blood flow significantly more than did dual ETA/ETB blockade (p < 0.05). These findings indicate that ET receptor blockade may be a new therapeutic strategy to improve coronary vascular function in patients with coronary artery disease.

scholarly journals Effect of Insulin Glulisine on Microvascular Blood Flow and Endothelial Function in the Postprandial State

Diabetes Care ◽  
2008 ◽  
Vol 31 (5) ◽  
pp. 1021-1025 ◽  
Author(s):  
C. Hohberg ◽  
T. Forst ◽  
M. Larbig ◽  
M. Safinowski ◽  
S. Diessel ◽  
...  
Keyword(s):  
Blood Flow ◽  
Endothelial Function ◽  
Microvascular Blood Flow ◽  
Postprandial State ◽  
Insulin Glulisine
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