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

2012 ◽  
Vol 113 (10) ◽  
pp. 1512-1518 ◽  
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.

scholarly journals Nitric oxide and cutaneous active vasodilation during heat stress in humans

1998 ◽  
Vol 85 (3) ◽  
pp. 824-829 ◽  
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.

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

1997 ◽  
Vol 272 (5) ◽  
pp. H2173-H2179 ◽  
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.

Cold-induced cutaneous vasoconstriction is mediated by Rho kinase in vivo in human skin

2007 ◽  
Vol 292 (4) ◽  
pp. H1700-H1705 ◽  
Author(s):  
Caitlin S. Thompson-Torgerson ◽  
Lacy A. Holowatz ◽  
Nicholas A. Flavahan ◽  
W. Larry Kenney
Keyword(s):  
Laser Doppler Flowmetry ◽  
Combined Treatment ◽  
Rho Kinase ◽  
Laser Doppler ◽  
Whole Body ◽  
Local Skin ◽  
Doppler Flowmetry ◽  
Thermoregulatory Model ◽  
Cutaneous Vasoconstriction

Cutaneous vasoconstriction (VC) is the initial thermoregulatory response to cold exposure and can be elicited through either whole body or localized skin cooling. However, the mechanisms governing local cold-induced VC are not well understood. We tested the hypothesis that Rho kinase participates in local cold-induced cutaneous VC. In seven men and women (20–27 yr of age), up to four ventral forearm skin sites were instrumented with intradermal microdialysis fibers for localized drug delivery during cooling. Skin blood flow was monitored at each site with laser-Doppler flowmetry while local skin temperature was decreased and maintained at 24°C for 40 min. Cutaneous vascular conductance (CVC; laser-Doppler flowmetry/mean arterial pressure) was expressed as percent change from 34°C baseline. During the first 5 min of cooling, CVC decreased at control sites (lactated Ringer solution) to −45 ± 6% ( P < 0.001), increased at adrenoceptor-antagonized sites (yohimbine + propranolol) to 15 ± 14% ( P = 0.002), and remained unchanged at both Rho kinase-inhibited (fasudil) and adrenoceptor-antagonized + Rho kinase-inhibited sites (yohimbine + propranolol + fasudil) (−9 ± 1%, P = 0.4 and −6 ± 2%, P = 0.4, respectively). During the last 5 min of cooling, CVC further decreased at all sites when compared with baseline values (control, −77 ± 4%, P < 0.001; adrenoceptor antagonized, −61 ± 3%, P < 0.001; Rho kinase inhibited, −34 ± 7%, P < 0.001; and adrenoceptor antagonized + Rho kinase inhibited sites, −35 ± 3%, P < 0.001). Rho kinase-inhibited and combined treatment sites were significantly attenuated when compared with both adrenoceptor-antagonized ( P < 0.01) and control sites ( P < 0.0001). Rho kinase mediates both early- and late-phase cold-induced VC, supporting in vitro findings and providing a putative mechanism through which both adrenergic and nonadrenergic cold-induced VC occurs in an in vivo human thermoregulatory model.

scholarly journals Methodological assessment of skin and limb blood flows in the human forearm during thermal and baroreceptor provocations

2010 ◽  
Vol 109 (3) ◽  
pp. 895-900 ◽  
Author(s):  
R. Matthew Brothers ◽  
Jonathan E. Wingo ◽  
Kimberly A. Hubing ◽  
Craig G. Crandall
Keyword(s):  
Blood Flow ◽  
Heat Stress ◽  
Doppler Ultrasound ◽  
Skin Blood Flow ◽  
Skin Surface ◽  
Laser Doppler ◽  
Whole Body ◽  
Surface Cooling ◽  
Doppler Flowmetry ◽  
Human Forearm

Skin blood flow responses in the human forearm, assessed by three commonly used technologies—single-point laser-Doppler flowmetry, integrated laser-Doppler flowmetry, and laser-Doppler imaging—were compared in eight subjects during normothermic baseline, acute skin-surface cooling, and whole body heat stress (Δ internal temperature = 1.0 ± 0.2°C; P < 0.001). In addition, while normothermic and heat stressed, subjects were exposed to 30-mmHg lower-body negative pressure (LBNP). Skin blood flow was normalized to the maximum value obtained at each site during local heating to 42°C for at least 30 min. Furthermore, comparisons of forearm blood flow (FBF) measures obtained using venous occlusion plethysmography and Doppler ultrasound were made during the aforementioned perturbations. Relative to normothermic baseline, skin blood flow decreased during normothermia + LBNP ( P < 0.05) and skin-surface cooling ( P < 0.01) and increased during whole body heating ( P < 0.001). Subsequent LBNP during whole body heating significantly decreased skin blood flow relative to control heat stress ( P < 0.05). Importantly, for each of the aforementioned conditions, skin blood flow was similar between the three measurement devices (main effect of device: P > 0.05 for all conditions). Similarly, no differences were identified across all perturbations between FBF measures using plethysmography and Doppler ultrasound ( P > 0.05 for all perturbations). These data indicate that when normalized to maximum, assessment of skin blood flow in response to vasoconstrictor and dilator perturbations are similar regardless of methodology. Likewise, FBF responses to these perturbations are similar between two commonly used methodologies of limb blood flow assessment.

Laser-Doppler flowmetry reveals rapid perfusion changes in adipose tissue of lean and obese females

2006 ◽  
Vol 291 (5) ◽  
pp. E1025-E1030 ◽  
Author(s):  
P. Wellhöner ◽  
D. Rolle ◽  
P. Lönnroth ◽  
L. Strindberg ◽  
M. Elam ◽  
...  
Keyword(s):  
Blood Flow ◽  
Adipose Tissue ◽  
Laser Doppler Flowmetry ◽  
Laser Doppler ◽  
Whole Body ◽  
Tissue Blood Flow ◽  
Flow Measurements ◽  
Doppler Flowmetry ◽  
Reflex Responses ◽  
Obese Subjects

The present study aimed to evaluate adipose tissue blood flow (ATBF) by means of laser-Doppler flowmetry (LDF) in humans. Lower body negative pressure (LBNP) and straining known to affect epidermal blood flow through the autonomic nervous system were performed in 11 lean and 11 obese female volunteers. ATBF changes were compared between both groups and also discriminated from skin blood flow (SBF) responses of the immediate vicinity. Additionally, LDF measurements were compared with flow measurements using 133xenon washout in 10 lean subjects during whole body cooling. LDF estimations of SBF and ATBF showed a positive correlation to 133Xe during cooling. SBF and ATBF were reduced to the same extent in both lean and obese subjects during LBNP. Straining induced divergent changes in SBF and ATBF: initially SBF decreased while ATBF increased, but toward the end of straining SBF increased above baseline and ATBF returned down to baseline level. Those changes were similar in both weight groups. Interestingly, only in obese subjects, both LBNP and straining were followed by ATBF augmentation, while SBF levels remained stable. In conclusion, LDF compares with 133Xe washout in monitoring ATBF during tonic perfusion changes. Its strength, however, lies in the detection of rapid flow alterations within the subcutaneous tissue, allowing the evaluation of reflex responses of the subcutaneous microcirculation. Interestingly, those rapid changes in SBF and ATBF can be both concordant and discordant. With regard to ATBF, vasoconstrictor components of the reflex responses were similar in lean and obese subjects, whereas vasodilatory responses were more pronounced in obese volunteers.

scholarly journals VIP/PACAP receptor mediation of cutaneous active vasodilation during heat stress in humans

2010 ◽  
Vol 109 (1) ◽  
pp. 95-100 ◽  
Author(s):  
Dean L. Kellogg ◽  
Joan L. Zhao ◽  
Yubo Wu ◽  
John M. Johnson
Keyword(s):  
Heat Stress ◽  
Baseline Period ◽  
Receptor Activation ◽  
Control Site ◽  
Whole Body ◽  
Pac1 Receptor ◽  
Doppler Flowmetry ◽  
Pituitary Adenylate Cyclase ◽  
Body Cooling ◽  
Cutaneous Vascular Conductance

Vasoactive intestinal peptide (VIP) is implicated in cutaneous active vasodilation in humans. VIP and the closely related pituitary adenylate cyclase activating peptide (PACAP) act through several receptor types: VIP through VPAC1 and VPAC2 receptors and PACAP through VPAC1, VPAC2, and PAC1 receptors. We examined participation of VPAC2 and/or PAC1 receptors in cutaneous vasodilation during heat stress by testing the effects of their specific blockade with PACAP6–38. PACAP6–38 dissolved in Ringer's was administered by intradermal microdialysis at one forearm site while a control site received Ringer's solution. Skin blood flow was monitored by laser-Doppler flowmetry (LDF). Blood pressure was monitored noninvasively and cutaneous vascular conductance (CVC) calculated. A 5- to 10-min baseline period was followed by ∼70 min of PACAP6–38 (100 μM) perfusion at one site in normothermia and a 3-min period of body cooling. Whole body heating was then performed to engage cutaneous active vasodilation and was maintained until CVC had plateaued at an elevated level at all sites for 5–10 min. Finally, 58 mM sodium nitroprusside was perfused through both microdialysis sites to effect maximal vasodilation. No CVC differences were found between control and PACAP6–38-treated sites during normothermia (19 ± 3%max untreated vs. 20 ± 3%max, PACAP6–38 treated; P > 0.05 between sites) or cold stress (11 ± 2%max untreated vs. 10 ± 2%max, PACAP6–38 treated, P > 0.05 between sites). PACAP6–38 attenuated the increase in CVC during whole body heating when compared with untreated sites (59 ± 3%max untreated vs. 46 ± 3%max, PACAP6–38 treated, P < 0.05). We conclude that VPAC2 and/or PAC1 receptor activation is involved in cutaneous active vasodilation in humans.

Peculiarities of microcirculation in periodont tissues in children of key age groups sufficient type 1 diabetes. Part II

2019 ◽  
Vol 24 (2) ◽  
pp. 108-119 ◽  
Author(s):  
B. N. Davydov ◽  
D. A. Domenyuk ◽  
S. V. Dmitrienko
Keyword(s):  
Diabetes Mellitus ◽  
Blood Flow ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Laser Doppler Flowmetry ◽  
Laser Doppler ◽  
Diabetic Microangiopathy ◽  
Healthy Children ◽  
Doppler Flowmetry

Relevance. Morpho-functional changes in peripheral circulation established in type 1 diabetes mellitus correlate with changes in central hemodynamics, allowing the use of microcirculation indicators as diagnostic and prognostic criteria for assessing the degree of functional vascular disorders. Identifcation of microcirculation features of the blood by the method of laser Doppler flowmetry in children with different experience of type 1 diabetes in key age categories.Materials and methods. The study included 67 children with type 1 diabetes mellitus aged 12-15 years with an experience of the disease from six months to ten years. The comparison group consisted of 38 healthy children. The state of the microvasculature was assessed by laser Doppler flowmetry using a laser analyzer for capillary blood flow LAKK-OP.Results. In children with an experience of type 1 diabetes of less than two years, microcirculation disorders in periodontal tissues correspond to the hyperemic form, accompanied by increased perfusion, a decrease in the amplitude of low-frequency oscillations, increased heart rate, high blood flling, and blood flow bypass. For children with an endocrinopathy experience of more than three years, microcirculation disorders correspond to a stagnant form, combined with a decrease in perfusion due to stagnation of blood in the venular link, endothelial domination with suppression of neurogenic and cardiac fluctuations, low efciency and redistribution of blood flow in favor of the nutritive link.Conclusions. With the increase in experience, the degree of compensation of type 1 diabetes, the progression of diabetic microangiopathy, it is advisable to designate two stages of development of microcirculatory disorders. Early – compensatory with active adaptation, including neurogenic and endothelial regulation mechanisms. Late – decompensation with passive adaptation, supporting the effectiveness of microcirculation due to myogenic control of regulation, shunting and increasing the rate of blood outflow.

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