scholarly journals Cutaneous blood flow and sweat rate responses to exogenous administration of acetylcholine and methacholine

2007 ◽  
Vol 102 (5) ◽  
pp. 1856-1861 ◽  
Author(s):  
Kenichi Kimura ◽  
David A. Low ◽  
David M. Keller ◽  
Scott L. Davis ◽  
Craig G. Crandall
Keyword(s):  
Blood Flow ◽  
Dose Response ◽  
Sweat Rate ◽  
Molar Concentration ◽  
Maximal Response ◽  
Cutaneous Blood Flow ◽  
Response Curves ◽  
Forearm Skin ◽  
Dose Response Curves ◽  
Cutaneous Blood

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.

Length-dependent sensitivity in vascular smooth muscle

1981 ◽  
Vol 241 (4) ◽  
pp. H557-H563 ◽  
Author(s):  
J. M. Price ◽  
D. L. Davis ◽  
E. B. Knauss
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Dose Response ◽  
Length Change ◽  
Maximal Response ◽  
Anterior Tibial Artery ◽  
Response Curves ◽  
Anterior Tibial ◽  
Dose Response Curves ◽  
Best Fit

Dose-response curves were obtained from dog anterior tibial artery rings at various lengths (L) to determine whether sensitivity to norepinephrine (NE) and potassium (K+) depends on arterial circumference. The dose for half maximal response (ED50) was determined by graphical estimation and by calculation from a best fit curve. For both NE and K+: 1) ED50 was lowest (most sensitive) at L for maximum active force (Lmax) and increased significantly as L decreased from Lmax; 2) ED50 at 1.0 and 1.15 Lmax was not significantly different; 3) ED50 of repeated dose-response curves at Lmax was not significantly different; and 4) when the direction of length change was reversed (from decreasing to increasing), the direction of change in ED50 was also reversed (from increasing to decreasing). Change in the dose for 10% maximal response was the same as ED50. The results did not depend on the method of determining ED50 or on whether responses were expressed as absolute values or as relative values. The results show that sensitivity of vascular smooth muscle depends on L and that the length-sensitivity relation is similar to the length-active tension relation. Similarity of results for NE and K+ indicate that length-dependent sensitivity does not depend on the method of stimulation.

Mechanical response of pulmonary artery under aerobic and hypoxic conditions

1977 ◽  
Vol 42 (3) ◽  
pp. 438-443
Author(s):  
J. F. Souhrada ◽  
D. W. Dickey
Keyword(s):  
Pulmonary Artery ◽  
Dose Response ◽  
Guinea Pigs ◽  
Main Pulmonary Artery ◽  
Maximal Response ◽  
Response Curves ◽  
Aerobic Conditions ◽  
Experimental Medium ◽  
Hypoxic Conditions ◽  
Dose Response Curves

The present study demonstrates the reactivity of isolated main pulmonary artery (MPA) from guinea pigs and rats to two vasoactive drugs, norepinephrine (NE) and histamine (H), in substrate-rich and substrate-free medium, under both aerobic (PO2 = 95 +/- 0.5 Torr) and hypoxic conditions (PO2 = 30 +/- 1 Torr). The sensitivity of MPA from guinea pigs to NE and H during aerobic conditions is not significantly affected by the absence of substrate in the experimental medium. Furthermore, it is demonstrated that in the substrate-rich experimental medium (5.5 mM glucose), the reactivity of MPA from guinea pigs to NE and H is not significantly affected by acute hypoxia as compared with the response of MPA during aerobic conditions. These experiments contrast with data obtained when substrate is absent from the experimental medium. The dose-response curves of MPA from guinea pigs to NE and H under this condition were significantly blunted during hypoxia. Following the completion of the dose-response curves during aerobic conditions, with both NE and H, spontaneous mechanical activities were seen in the guinea pig MPA. On the other hand, it was demonstrated that during aerobic and hypoxic conditions MPA's isolated from rats exhibit no physiological response to histamine even when administered in the dose required to produce the maximal response in MPA isolated from guinea pigs. The sensitivity of MPA from rats to NE during aerobic conditions is not significantly affected by the absence of substrate in the experimental medium. However, when the preparation was exposed to hypoxia, the presence of substrate failed to maintain the reactivity of MPA to norepinephrine. In addition, MPA isolated from rats demonstrated a smaller contractile response to NE than those from guinea pigs. Furthermore, no spontaneous mechanical activities were observed after norepinephrine or histamine administration. The present study, in addition to pointing out species differences, shows the important role of exogenous substrate in maintaining the reactivity of pulmonary vascular smooth muscle during hypoxia.

A General Measure of In Vitro Phototoxicity Derived from Pairs of Dose-Response Curves and its Use for Predicting the In Vivo Phototoxicity of Chemicals

1997 ◽  
Vol 25 (4) ◽  
pp. 445-462 ◽  
Author(s):  
Hermann-Georg Holzhütter
Keyword(s):  
Dose Response ◽  
Uv Light ◽  
Test System ◽  
Maximal Response ◽  
Response Curves ◽  
General Measure ◽  
Absolute Change ◽  
Response Data ◽  
Dose Response Curves ◽  
The Absolute

In pharmacology, it is common to evaluate the influence of external effectors (for example, temperature, pH, and presence of a second drug) on dose-response relations by the potency factor (PF50): [Formula: see text] where ED50 (± effector) denotes the 50% effective dose in the presence and in the absence of the effector, respectively. In this paper, the external effector is ultraviolet (UV) light, and PF50 is referred to as the photoirritancy factor (PIF). There are two parameters which limit the applicability and toxicological reliability of the PIF. Firstly, the physical properties (for example, water solubility) of the chemical tested and the constraints of the biological test system may make it difficult, or even impossible, to achieve sufficiently high doses to observe 50% of the maximal response. In such cases, no numeric value of the potency factor can be computed. Secondly, the potency factor does not take into account the absolute change in response induced by UV light, i.e. depending on the shape of the ±UV dose-response curves, the absolute change in response may be small although the PIF is large, and vice versa. This paper proposes a more general measure of phototoxicity, the mean photo effect (MPE), which can be assessed from pairs of dose-response curves, even if the 50% response level is not reached in one curve or in both. The MPE is a weighted average of PIFd values across different dose levels (d being common to both dose-response curves). The absolute response changes, ΔRd, i.e. the differences between the -UV curve and the +UV curve are used as weighting factors. The numerical computation of the MPE is based on theoretical curves obtained by fitting a mathematical model to the experimental dose-response data. Plotting PIFd and ΔRd versus the corresponding doses permits differences in the shapes of the two curves to be assessed, and possible alterations in the toxic mechanisms induced by UV light to be revealed. The variance of MPE is estimated by a bootstrap procedure. The use of the MPE is illustrated by its application to dose-response data obtained with a human keratinocyte assay of fibroblasts in the EU/COLIPA international validation project on photoirritancy.

Circadian rhythm in sweating and cutaneous blood flow

1984 ◽  
Vol 246 (3) ◽  
pp. R321-R324 ◽  
Author(s):  
L. A. Stephenson ◽  
C. B. Wenger ◽  
B. H. O'Donovan ◽  
E. R. Nadel
Keyword(s):  
Blood Flow ◽  
Circadian Rhythm ◽  
Body Temperature ◽  
Forearm Blood Flow ◽  
Sweat Rate ◽  
Circadian Variation ◽  
Esophageal Temperature ◽  
Cutaneous Blood Flow ◽  
Cutaneous Vasodilation ◽  
Cutaneous Blood

To characterize the changes in the control of the heat loss responses associated with the circadian variation in body temperature, we studied five men during 20 min of exercise in 25 degrees C on 6 separate days. Experiments were conducted at six times, equally spaced over the 24-h day. Esophageal temperature (Tes) and chest sweat rate (msw) were measured continuously, and forearm blood flow (FBF) was measured one to two times per minute. The thresholds for sweating and forearm vasodilation were significantly higher at 1600 and 2000 than at 2400 and 0400, averaging 0.57 and 0.65 degrees C higher, respectively, at 1600 than at 0400. Resting Tes and the Tes thresholds for cutaneous vasodilation and sweating during exercise all showed a similar circadian rhythm. The level at which core temperature is regulated therefore varies over the 24-h day with the zenith occurring around 1600 and the nadir at 0400. However, whereas the slope of the msw-to-Tes relation did not change over the 24-h day, the slope of the FBF-to-Tes relation tended to increase between 0400 and 2400, implying that the circadian rhythm may be more complex than just a shift in the central reference temperature.

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 ◽  
...  
Keyword(s):  
Older Adults ◽  
Blood Flow ◽  
Young Adults ◽  
Cutaneous Blood Flow ◽  
No Donor ◽  
Kca Channels ◽  
Cox Inhibitor ◽  
Forearm Skin ◽  
Channel Dependent ◽  
Cutaneous Blood

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.

scholarly journals Effects of atropine and l-NAME on cutaneous blood flow during body heating in humans

2000 ◽  
Vol 88 (2) ◽  
pp. 467-472 ◽  
Author(s):  
Shubha Shastry ◽  
Christopher T. Minson ◽  
Shurea A. Wilson ◽  
Niki M. Dietz ◽  
Michael J. Joyner
Keyword(s):  
Blood Flow ◽  
Receptor Activation ◽  
No Synthase ◽  
Cutaneous Blood Flow ◽  
Cutaneous Vasodilation ◽  
Forearm Skin ◽  
Synthase Inhibitor ◽  
Cutaneous Vascular Conductance ◽  
Cutaneous Blood ◽  
Doppler Flowmeter

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.

Length-dependent sensitivity at lengths greater than Lmax in vascular smooth muscle

1983 ◽  
Vol 245 (3) ◽  
pp. H379-H384 ◽  
Author(s):  
J. M. Price ◽  
D. L. Davis ◽  
E. B. Knauss
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Dose Response ◽  
Muscle Length ◽  
Maximal Response ◽  
Anterior Tibial Artery ◽  
Active Force ◽  
Response Curves ◽  
Active Stress ◽  
Dose Response Curves

Previous work has shown that vascular smooth muscle sensitivity depends on muscle length (arterial circumference) at lengths equal to and less than that for maximum active force (Lmax). In the present study dose-response curves were obtained from dog anterior tibial artery rings at lengths equal to or longer than Lmax. The curves were compared with dose-response curves obtained at lengths less than Lmax. The agonist concentration for half maximal response (ED50) was determined by graphical estimation and by calculation from a best-fit curve. The results show that with norepinephrine (NE) stimulation 1) ED50 decreased significantly at each step when the rings were stretched from Lmax to 1.15 Lmax and then to 1.30 Lmax; 2) ED50 increased significantly when length was decreased from 1.15 to 1.00 Lmax; 3) ED50 decreased significantly at each step when the rings were stretched from 0.70 Lmax to Lmax and then to 1.30 Lmax; and 4) for NE concentration greater than the ED50 at Lmax, active stress was significantly higher at Lmax than at 0.70 Lmax or 1.30 Lmax. For an NE concentration less than the ED50 at Lmax, the active stress at 1.30 Lmax was higher than the active stress at Lmax and at 0.70 Lmax. The results show that sensitivity of vascular smooth muscle continually increases with stretch and does not have a maximum at the length for maximum active force.

Intestinal microvascular responsiveness to norepinephrine in chronic portal hypertension

1991 ◽  
Vol 260 (4) ◽  
pp. H1135-H1143 ◽  
Author(s):  
T. Joh ◽  
D. N. Granger ◽  
J. N. Benoit
Keyword(s):  
Blood Flow ◽  
Portal Hypertension ◽  
Dose Response ◽  
Vessel Diameter ◽  
Maximal Response ◽  
Hypertensive Rats ◽  
Response Curves ◽  
Cross Sectional ◽  
On Line

Effects of chronic prehepatic portal hypertension on intestinal microvascular sensitivity to norepinephrine (NE) were studied. Normal and portal hypertensive rats were anesthetized, and the intestine was prepared for in vivo microscopic observation. The preparation was transferred to a video microscope and a first-, second-, or third-order submucosal arteriole (i.e., 1A, 2A, or 3A, respectively) selected for study. Microvascular diameter and arteriolar erythrocyte velocity were measured on-line, and arteriolar blood flow was subsequently calculated as the product of velocity and vessel cross-sectional area. Once steady-state conditions were reached, the preparation was exposed to incremental doses of NE and microvessel responses were recorded. Cumulative log dose-response curves relating the change in arteriolar blood flow and vessel diameter to NE concentration were constructed for each group of arterioles and the ED50 for maximal response obtained from each dose-response relationship. NE ED50 for 1A blood flow was significantly higher in portal hypertensive rats (2.57 +/- 0.25 microM) compared with control rats (1.48 +/- 0.19 microM). Analysis of the diameter responses of 1A, 2A, and 3A indicated that the loss of vascular NE sensitivity in chronic portal hypertension was localized to the terminal submucosal arterioles (2A and 3A). No differences in the diameter response of 1A were observed between normal and portal hypertensive rats. Separate experiments were conducted to test if glucagon, a known mediator of the hyperdynamic intestinal circulation in portal hypertension, could acutely alter NE responsiveness in normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis and comparison of sigmoidal curves: application to dose-response data

1989 ◽  
Vol 257 (6) ◽  
pp. G982-G989 ◽  
Author(s):  
J. B. Meddings ◽  
R. B. Scott ◽  
G. H. Fick
Keyword(s):  
Nonlinear Regression ◽  
Dose Response ◽  
Numerical Solutions ◽  
Maximal Response ◽  
Response Curves ◽  
Experimental Conditions ◽  
Response Data ◽  
Accuracy And Precision ◽  
Analysis Technique ◽  
Dose Response Curves

A number of physiological or pharmacological studies generate sigmoidal dose-response curves. Ideally, data analysis should provide numerical solutions for curve parameters. In addition, for curves obtained under different experimental conditions, testing for significant differences should be easily performed. We have reviewed the literature over the past 3 years in six journals publishing papers in the field of gastrointestinal physiology and established the curve analysis technique used in each. Using simulated experimental data of known error structure, we have compared these techniques with nonlinear regression analysis. In terms of their ability to provide accurate estimates of ED50 and maximal response, none approached the accuracy and precision of nonlinear regression. This technique is as easily performed as the classic methods and additionally provides an opportunity for rigorous statistical analysis of data. We present a method of determining the significance of differences found in the ED50 and maximal response under different experimental conditions. The method is versatile and applicable to a variety of different physiological and pharmacological dose-response curves.

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