scholarly journals Cutaneous blood flow during intradermal NO administration in young and older adults: roles for calcium-activated potassium channels and cyclooxygenase?

2016 ◽  
Vol 310 (11) ◽  
pp. R1081-R1087 ◽  
Author(s):  
Naoto Fujii ◽  
Robert D. Meade ◽  
Christopher T. Minson ◽  
Vienna E. Brunt ◽  
Pierre Boulay ◽  
...  

Nitric oxide (NO) increases cutaneous blood flow; however, the underpinning mechanism(s) remains to be elucidated. We hypothesized that the cutaneous blood flow response during intradermal administration of sodium nitroprusside (SNP, a NO donor) is regulated by calcium-activated potassium (KCa) channels and cyclooxygenase (COX) in young adults. We also hypothesized that these contributions are diminished in older adults given that aging can downregulate KCa channels and reduce COX-derived vasodilator prostanoids. In 10 young (23 ± 5 yr) and 10 older (54 ± 4 yr) adults, cutaneous vascular conductance (CVC) was measured at four forearm skin sites infused with 1) Ringer (Control), 2) 50 mM tetraethylammonium (TEA), a nonspecific KCa channel blocker, 3) 10 mM ketorolac, a nonspecific COX inhibitor, or 4) 50 mM TEA + 10 mM ketorolac via intradermal microdialysis. All skin sites were coinfused with incremental doses of SNP (0.005, 0.05, 0.5, 5, and 50 mM each for 25 min). During SNP administration, CVC was similar at the ketorolac site (0.005–50 mM, all P > 0.05) relative to Control, but lower at the TEA and TEA + ketorolac sites (0.005–0.05 mM, all P < 0.05) in young adults. In older adults, ketorolac increased CVC relative to Control during 0.005–0.05 mM SNP administration (all P < 0.05), but this increase was not observed when TEA was coadministered (all P > 0.05). Furthermore, TEA alone did not modulate CVC during any concentration of SNP administration in older adults (all P > 0.05). We show that during low-dose NO administration (e.g., 0.005–0.05 mM), KCa channels contribute to cutaneous blood flow regulation in young adults; however, in older adults, COX inhibition increases cutaneous blood flow through a KCa channel-dependent mechanism.

2000 ◽  
Vol 88 (2) ◽  
pp. 467-472 ◽  
Author(s):  
Shubha Shastry ◽  
Christopher T. Minson ◽  
Shurea A. Wilson ◽  
Niki M. Dietz ◽  
Michael J. Joyner

We sought to investigate further the roles of sweating, ACh spillover, and nitric oxide (NO) in the neurally mediated cutaneous vasodilation during body heating in humans. Six subjects were heated with a water-perfused suit while cutaneous blood flow was measured with a laser-Doppler flowmeter. After a rise in core temperature (1.0 ± 0.1°C) and the establishment of cutaneous vasodilation, atropine and subsequently the NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME) were given to the forearm via a brachial artery catheter. After atropine infusion, cutaneous vascular conductance (CVC) remained constant in five of six subjects, whereasl-NAME administration blunted the rise in CVC in three of six subjects. A subsequent set of studies using intradermal microdialysis probes to selectively deliver drugs into forearm skin confirmed that atropine did not affect CVC. However, perfusion ofl-NAME resulted in a significant decrease in CVC (37 ± 4%, P < 0.05). The results indicate that neither sweating nor NO release via muscarinic receptor activation is essential to sustain cutaneous dilation during heating in humans.


2007 ◽  
Vol 102 (5) ◽  
pp. 1856-1861 ◽  
Author(s):  
Kenichi Kimura ◽  
David A. Low ◽  
David M. Keller ◽  
Scott L. Davis ◽  
Craig G. Crandall

The aim of this study was to evaluate cutaneous vasodilation and sweating responses to exogenous administration of acetylcholine (ACh) and methacholine (MCh), which have different sensitivities to endogenous cholinesterase. Four intradermal microdialysis probes were placed in dorsal forearm skin: two sites were perfused with ACh (1 × 10−7–1 M) and the other two with the same molar concentrations of MCh. Sweat rate (SR) and cutaneous blood flow were simultaneously assessed directly over each microdialysis membrane. Dose-response curves were constructed, and the effective concentration of the drug resulting in 50% of the maximal response (EC50) was identified. For SR and cutaneous vascular conductance (CVC), there were no significant differences in EC50 between sites receiving the same drug: −1.52 ± 0.18 and −1.19 ± 0.09 log-molar concentration of ACh at distal and proximal sites, respectively, and −2.35 ± 0.24 and −2.42 ± 0.23 log-molar concentration of MCh at distal and proximal sites, respectively, for SR ( P > 0.05) and −3.87 ± 0.32 and −3.97 ± 0.27 log-molar concentration of ACh at distal and proximal sites, respectively, and −4.78 ± 0.17 and −4.46 ± 0.16 log-molar concentration of MCh at distal and proximal sites, respectively, for CVC ( P > 0.05). However, the EC50 for CVC and SR was significantly lower at the MCh than at the ACh sites. A second procedure was performed to confirm that differences in responses between ACh and MCh could be attributed to different cholinesterase sensitivities. Similarly, four microdialysis membranes were placed in dorsal forearm skin: two sites were perfused with ACh and other two with MCh. However, one of each of the ACh and MCh sites was also perfused with 10 μM neostigmine (an acetylcholinesterase inhibitor). Neostigmine at the ACh site induced a leftward shift (i.e., lower EC50) of the SR and CVC dose-response curves compared with the site treated with ACh alone, resulting in no difference in the EC50 for SR and CVC between the ACh + neostigmine and the MCh site. These results suggest that elevations in SR and CVC occur earlier with MCh than with ACh treatment because of differences in cholinesterase susceptibility between these drugs.


1997 ◽  
Vol 59 (2) ◽  
pp. 255-256
Author(s):  
Yuka NAKAMURA ◽  
Shinichi WATANABE ◽  
Hisashi TAKAHASHI ◽  
Atsuhiko HASEGAWA

1963 ◽  
Vol 18 (4) ◽  
pp. 781-785 ◽  
Author(s):  
Leo C. Senay ◽  
Leon D. Prokop ◽  
Leslie Cronau ◽  
Alrick B. Hertzman

The relationship of local skin temperature and the onset of sweating to the local cutaneous blood flow was studied in the forearm and calf. The purpose of the investigation was to appraise the possible relation of sweat gland activity to the cutaneous vasodilatation which has been attributed to bradykinin or to intracranial temperatures. The onset of sweating was not marked by any apparently related increases in the rate of cutaneous blood flow. On the contrary, the onset of sweating was followed often by a stabilization or even a decrease in the level of cutaneous blood flow. The relations of the latter to the local skin temperature were complex, particularly in the forearm. There appeared to be additional unidentified influences, possibly vasomotor, operating on the skin vessels during transitional phases in the relation of skin temperature to blood flow. Submitted on October 15, 1962


1989 ◽  
Vol 2 (4) ◽  
pp. 198-203 ◽  
Author(s):  
F. Auclair ◽  
M. Besnard ◽  
C. Dupont ◽  
J. Wepierre

1965 ◽  
Vol 20 (5) ◽  
pp. 975-979 ◽  
Author(s):  
Leo C. Senay ◽  
Margaret L. Christensen

The experiments reported are concerned with cardiovascular and sudomotor events preceding, accompanying, and following ingestion of water by five dehydrating subjects 8.75 hr after entrance into a heat chamber (43.3 C DB, 29 C WB). Certain skin areas such as the cheek showed increases in evaporative heat loss before subjects came in contact with water. This reflex could be initiated by saline ingestion but the degree of skin and oral temperature changes appeared to depend on tonicity of fluid ingested. The gustatory reflex was not thought to be the initiating agent for sudomotor responses. Increases in cutaneous blood flow appeared to begin almost as promptly as sweating responses but took considerably longer to develop. Ingestion of saline, though initiating a sweating response, did not alter heart rate, blood pressure, or cutaneous blood flow. It is suggested that fluid ingestion, regardless of tonicity, triggers reflex sweating over the body surface. Intensity and duration of this sudomotor response, as well as initiation of cardiovascular changes, apparently depend on tonicity of ingested fluid. cutaneous blood flow; skin temperature; regional sweating Submitted on November 27, 1964


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