Regulation of human cutaneous circulation evaluated by laser Doppler flowmetry, iontophoresis, and spectral analysis: importance of nitric oxide and prostaglandines

We tested the hypothesis that cyclooxygenases (COXs) or COX products inhibit nitric oxide (NO) synthesis and thereby mask potential effects of NO on reactive hyperemia in the cutaneous circulation. We performed laser-Doppler flowmetry (LDF) with intradermal microdialysis in 12 healthy volunteers aged 19–25 yr. LDF was expressed as the percent cutaneous vascular conduction (%CVC) or as the maximum %CVC (%CVCmax) where CVC is LDF/mean arterial pressure. We tested the effects of the nonisoform-specific NO synthase inhibitor nitro-l-arginine (NLA, 10 mM), the nonspecific COX inhibitor ketorolac (Keto, 10 mM), combined NLA + Keto, and NLA + sodium nitroprusside (SNP, 28 mM) on baseline and reactive hyperemia flow parameters. We also examined the effects of isoproterenol, a β-adrenergic agonist that causes prostaglandin-independent vasodilation to correct for the increase in baseline flow caused by Keto. When delivered directly into the intradermal space, Keto greatly augments all aspects of the laser-Doppler flow response to reactive hyperemia: peak reactive hyperemic flow increased from 41 ± 5 to 77 ± 7%CVCmax, time to peak flow increased from 17 ± 3 to 56 ± 24 s, the area under the reactive hyperemic curve increased from 1,417 ± 326 to 3,376 ± 876%CVCmax·s, and the time constant for the decay of peak flow increased from 100 ± 23 to 821 ± 311 s. NLA greatly attenuates the Keto response despite exerting no effects on baseline LDF or on reactive hyperemia when given alone. Low-dose NLA + SNP duplicates the Keto response. Isoproterenol increased baseline and peak reactive flow. These results suggest that COX inhibition unmasks NO dependence of reactive hyperemia in human cutaneous circulation.

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Nitric oxide and cutaneous active vasodilation during heat stress in humans

Journal of Applied Physiology ◽

10.1152/jappl.1998.85.3.824 ◽

1998 ◽

Vol 85 (3) ◽

pp. 824-829 ◽

Cited By ~ 219

Author(s):

D. L. Kellogg ◽

C. G. Crandall ◽

Y. Liu ◽

N. Charkoudian ◽

J. M. Johnson

Keyword(s):

Nitric Oxide ◽

Heat Stress ◽

Laser Doppler Flowmetry ◽

Sweat Rate ◽

Ringer Solution ◽

No Synthase ◽

Laser Doppler ◽

Vascular Conductance ◽

Doppler Flowmetry ◽

Cutaneous Vascular Conductance

Whether nitric oxide (NO) is involved in cutaneous active vasodilation during hyperthermia in humans is unclear. We tested for a role of NO in this process during heat stress (water-perfused suits) in seven healthy subjects. Two forearm sites were instrumented with intradermal microdialysis probes. One site was perfused with the NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME) dissolved in Ringer solution to abolish NO production. The other site was perfused with Ringer solution only. At those sites, skin blood flow (laser-Doppler flowmetry) and sweat rate were simultaneously and continuously monitored. Cutaneous vascular conductance, calculated from laser-Doppler flowmetry and mean arterial pressure, was normalized to maximal levels as achieved by perfusion with the NO donor nitroprusside through the microdialysis probes. Under normothermic conditions,l-NAME did not significantly reduce cutaneous vascular conductance. During hyperthermia, with skin temperature held at 38–38.5°C, internal temperature rose from 36.66 ± 0.10 to 37.34 ± 0.06°C ( P < 0.01). Cutaneous vascular conductance at untreated sites increased from 12 ± 2 to 44 ± 5% of maximum, but only rose from 13 ± 2 to 30 ± 5% of maximum at l-NAME-treated sites ( P < 0.05 between sites) during heat stress. l-NAME had no effect on sweat rate ( P > 0.05). Thus cutaneous active vasodilation requires functional NO synthase to achieve full expression.

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Role of nitric oxide in vasodilator response induced by salbutamol in rat diaphragmatic microcirculation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.272.5.h2173 ◽

1997 ◽

Vol 272 (5) ◽

pp. H2173-H2179 ◽

Cited By ~ 3

Author(s):

H. Y. Chang

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Cyclic Amp ◽

Laser Doppler Flowmetry ◽

Ringer Solution ◽

Laser Doppler ◽

Microvascular Blood Flow ◽

Doppler Flowmetry ◽

Vasodilator Response

To determine the contribution of nitric oxide (NO) to the vasodilator response induced by salbutamol in diaphragmatic microcirculation, we studied a diaphragmatic preparation in anesthetized rats. With bicarbonate-buffered Ringer solution continuously suffusing the diaphragm, laser-Doppler flowmetry was used to record microvascular blood flow (QLDF). The drugs were applied to the surface of the diaphragm. Salbutamol (3.2 x 10(-7)-10(-4) M), isoproterenol (3.2 x 10(-8)-3.2 x 10(-6) M), and forskolin (3.2 x 10(-7)-10(-5) M) each elicited a concentration-dependent increase in QLDF. The vasodilator response induced by salbutamol (3.2 x 10(-7), 10(-6), and 3.2 x 10(-6) M) was attenuated by a 15-min suffusion of N omega-nitro-L-arginine (L-NNA, 10(-4) M), and pretreatment with L-arginine (10(-2) M) could restore salbutamol-induced vasodilator responses. Salbutamol-induced vasodilation was also abolished by propranolol (10(-5) M). Similarly, the vasodilator response elicited by isoproterenol (3.2 x 10(-8), 10(-7), and 3.2 x 10(-7) M) and forskolin (3.2 x 10(-7), 10(-6), and 3.2 x 10(-6) M) was inhibited by L-NNA (10(-4) M). In contrast, the vasodilator response induced by adenosine (10(-6), 10(-5), and 10(-4) M) was not affected by L-NNA (10(-4) M). These data indicate that in rat diaphragmatic microcirculation salbutamol-induced vasodilation may be partly mediated by beta-adrenoceptors on the endothelium. Moreover, these data suggest that an elevation of cyclic AMP in the endothelium may cause release of NO.

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Spectral analysis of laser Doppler flowmetry signals

2012 IEEE 2nd Portuguese Meeting in Bioengineering (ENBENG) ◽

10.1109/enbeng.2012.6331342 ◽

2012 ◽

Cited By ~ 3

Author(s):

Rita Campos ◽

Edite Figueiras ◽

Luis F. Requicha Ferreira ◽

Anne Humeau-Heurtier

Keyword(s):

Spectral Analysis ◽

Laser Doppler Flowmetry ◽

Laser Doppler ◽

Doppler Flowmetry

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Laser doppler flowmetry for estimating microcirculatory function in response to prolonged inhaled nitric oxide applications

BIOPHYSICS ◽

10.1134/s000635091705013x ◽

2017 ◽

Vol 62 (5) ◽

pp. 853-856

Author(s):

A. K. Martusevich ◽

P. V. Peretyagin ◽

A. A. Martusevich ◽

S. P. Peretyagin

Keyword(s):

Nitric Oxide ◽

Laser Doppler Flowmetry ◽

Inhaled Nitric Oxide ◽

Laser Doppler ◽

Doppler Flowmetry ◽

Microcirculatory Function

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Nitric oxide and receptors for VIP and PACAP in cutaneous active vasodilation during heat stress in humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.00859.2012 ◽

2012 ◽

Vol 113 (10) ◽

pp. 1512-1518 ◽

Cited By ~ 18

Author(s):

Dean L. Kellogg ◽

Joan L. Zhao ◽

Yubo Wu ◽

John M. Johnson

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Heat Stress ◽

Laser Doppler Flowmetry ◽

Combined Treatment ◽

Receptor Activation ◽

Laser Doppler ◽

Whole Body ◽

Pac1 Receptor ◽

Doppler Flowmetry

VPAC2 receptors sensitive to vasoactive intestinal polypeptide (VIP) and pituitary adenylyl cyclase activating polypeptide (PACAP), PAC1 receptors sensitive to PACAP, and nitric oxide (NO) generation by NO synthase (NOS) are all implicated in cutaneous active vasodilation (AVD) through incompletely defined mechanisms. We hypothesized that VPAC2/PAC1 receptor activation and NO are synergistic and interdependent in AVD and tested our hypothesis by examining the effects of VPAC2/PAC1 receptor blockade with and without NOS inhibition during heat stress. The VPAC2/PAC1 antagonist, pituitary adenylate cyclase activating peptide 6–38 (PACAP6–38) and the NOS inhibitor, NG-nitro-l-arginine methyl ester (l-NAME) were administered by intradermal microdialysis. PACAP6–38, l-NAME, a combination of PACAP6–38 and l-NAME, or Ringer's solution alone were perfused at four separate sites. Skin blood flow was monitored by laser-Doppler flowmetry at each site. Body temperature was controlled with water-perfused suits. Blood pressure was monitored by Finapres, and cutaneous vascular conductance (CVC) calculated (CVC = laser-Doppler flowmetry/mean arterial pressure). The protocol began with a 5- to 10-min baseline period without antagonist perfusion, followed by perfusion of PACAP6–38, l-NAME, or combined PACAP6–38 and l-NAME at the different sites in normothermia (45 min), followed by 3 min of whole body cooling. Whole body heating was then performed to induce heat stress and activate AVD. Finally, 58 mM sodium nitroprusside were perfused at all sites to effect maximal vasodilation for normalization of blood flow data. No significant differences in CVC (normalized to maximum) were found among Ringer's PACAP6–38, l-NAME, or combined antagonist sites during normothermia ( P > 0.05 among sites) or cold stress ( P > 0.05 among sites). CVC responses at all treated sites were attenuated during AVD ( P < 0.05 vs. Ringer's). Attenuation was greater at l-NAME and combined PACAP6–38- and l-NAME-treated sites than at PACAP6–38 sites ( P > 0.05). Because responses did not differ between l-NAME and combined treatment sites ( P > 0.05), we conclude that VPAC2/PAC1 receptors require NO in series to effect AVD.

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