Effect of age on cutaneous vasoconstrictor responses to norepinephrine in humans

2004 ◽  
Vol 287 (5) ◽  
pp. R1230-R1234 ◽  
Author(s):  
Thad E. Wilson ◽  
Kevin D. Monahan ◽  
Daniel S. Short ◽  
Chester A. Ray

To test the hypothesis that cutaneous vasoconstrictor responsiveness to exogenous norepinephrine is reduced in older compared with young subjects, dose-response relations between norepinephrine and skin blood flow were established. Seven doses of norepinephrine (1·10−8 to 10−2 log M) were perfused (2 μl/min) intradermally (4 min/dose) using cutaneous microdialysis (2 probes/subject). To account for possible differences in endogenous norepinephrine between groups, one microdialysis probe was perfused with bretylium tosylate to locally block noradrenergic vesicle release before establishing the norepinephrine dose-response relations. Skin blood flow was indexed via laser-Doppler flowmetry directly over both microdialysis probe sites and is expressed as cutaneous vascular conductance (laser-Doppler flux/mean arterial blood pressure). Local skin temperature was maintained at 34°C at both sites throughout the protocol. Dose-response relation between norepinephrine and cutaneous vascular conductance was similar between control and bretylium-pretreated sites in young subjects (EC50 = −5.18 ± 0.27 and −5.03 ± 0.27 log M, respectively). In contrast, the dose-response relation was significantly shifted to the right (i.e., a higher dose of norepinephrine was needed to produce the same vasoconstrictor response) in the bretylium-pretreated site in older subjects (EC50 = −5.46 ± 0.23 and −4.53 ± 0.23 log M, respectively). Significant increases in EC50 were observed in older compared with young subjects at the bretylium-pretreated but not the control sites. These data indicate that cutaneous vasoconstrictor responsiveness is decreased in older subjects when endogenous release of norepinephrine is antagonized. Furthermore, these findings suggest that differences in presynaptic norepinephrine release between older and younger subjects are profound enough to affect dose-response relations between norepinephrine and cutaneous vascular conductance.

2008 ◽  
Vol 105 (5) ◽  
pp. 1504-1508 ◽  
Author(s):  
Manabu Shibasaki ◽  
David A. Low ◽  
Scott L. Davis ◽  
Craig G. Crandall

Previously, we found that nitric oxide (NO) inhibits cutaneous vasoconstrictor responsiveness evoked by whole body cooling, as well as an orthostatic stress in the heat-stressed human (Shibasaki M, Durand S, Davis SL, Cui J, Low DA, Keller DM, Crandall CG. J Physiol 585: 627–634, 2007). However, it remains unknown whether this response occurs via NO acting through presynaptic or postsynaptic mechanisms. The aim of this study was to test the hypothesis that NO is capable of impairing cutaneous vasoconstriction via postsynaptic mechanisms. Skin blood flow was monitored over two forearm sites where intradermal microdialysis membranes were previously placed. Skin blood flow was elevated four- to fivefold through perfusion of the NO donor sodium nitroprusside at one site and through perfusion of adenosine (primarily non-NO mechanisms) at a second site. Once a plateau in vasodilation was evident, increasing concentrations of norepinephrine (1 × 10−8 to 1 × 10−2 M) were administrated through both microdialysis probes, while the aforementioned vasodilator agents continued to be perfused. Cutaneous vascular conductance was calculated by dividing skin blood flow by mean arterial blood pressure. The administration of norepinephrine decreased cutaneous vascular conductance at both sites. However, the dose of norepinephrine at the onset of vasoconstriction (−5.9 ± 1.3 vs. −7.2 ± 0.7 log M norepinephrine, P = 0.021) and the concentration of norepinephrine resulting in 50% of the maximal vasoconstrictor response (−4.9 ± 1.2 vs. −6.1 ± 0.2 log M norepinephrine dose; P = 0.012) occurred at significantly higher norepinephrine concentrations for the sodium nitroprusside site relative to the adenosine site, respectively. These results suggested that NO is capable of attenuating cutaneous vasoconstrictor responsiveness to norepinephrine via postsynaptic mechanisms.


2011 ◽  
Vol 122 (6) ◽  
pp. 271-279 ◽  
Author(s):  
Laurence G. Trahair ◽  
Lora Vanis ◽  
Diana Gentilcore ◽  
Kylie Lange ◽  
Christopher K. Rayner ◽  
...  

PPH (postprandial hypotension), leading to increased morbidity and mortality, is an important clinical problem, particularly in the elderly and individuals with autonomic dysfunction. The magnitude of the postprandial fall in BP (blood pressure) appears to be dependent on the rate of nutrient entry into the small intestine and may be related to changes in splanchnic blood flow and sympathetic nerve activity. We aimed at determining the comparative effects of different ID (intraduodenal) glucose loads on BP, HR (heart rate), SMA (superior mesenteric artery) flow and vascular conductance and plasma NA (noradrenaline) in ‘young’ and ‘older’ subjects. A total of 12 ‘young’ (six male and six female; age, 22.2±2.3 years) and 12 ‘older’ (six male and six female; age, 68.7±1.0 years) subjects, the latter who have been studied previously [Vanis, Gentilcore, Rayner, Wishart, Horowitz, Feinle-Bisset and Jones (2011) Am. J. Physiol. Regul. Integr. Comp. Physiol., 300, R1524–R1531], had measurements of BP, HR, SMA flow and plasma NA before, and during, ID infusions of glucose at 1, 2 or 3 kcal/min (‘G1’, ‘G2’ and ‘G3’) (where 1 kcal≈4.184 J), or ‘S’ (saline) for 60 min. In ‘young’ subjects, there was no change in BP during any of the four infusions. In contrast, in ‘older’ subjects, SBP (systolic BP) fell during ‘G2’, and ‘G3’ (P<0.005 for both), but not during ‘S’ or ‘G1’. In ‘young’ and ‘older’ subjects HR increased during ‘G2’ (P<0.05) and ‘G3’ (P<0.001), a response that was greater (P<0.05) in the young, but not during ‘S’ or ‘G1’. The rise in SMA flow and vascular conductance in response to ID glucose were load-dependent in both ‘young’ and ‘older’ subjects (P<0.001 for all), with no difference between them. Plasma NA rose in response to ‘G2’ and ‘G3’ (P<0.05) in the young, but in ‘G3’ (P<0.05) only in the ‘older’ subjects, with no difference between them. Hence, in response to small intestinal glucose infusions at 1, 2 and 3 kcal/min, ‘older’, but not ‘young’, subjects exhibit a comparable fall in BP in response to the two higher glucose loads, which may reflect an inadequate, compensatory, rise in HR, in the ‘older’ subjects, but not a greater increase in SMA conductance.


2013 ◽  
Vol 304 (7) ◽  
pp. R566-R573 ◽  
Author(s):  
Caroline J. Smith ◽  
W. Larry Kenney ◽  
Lacy M. Alexander

Regional variation in sweating over the human body is widely recognized yet variation in vasomotor responses and mechanisms causing this variation remain unclear. This study aimed to explore the relation between regional sweating rates (RSR) and skin blood flow (SkBF) responses to thermal and pharmacological stimuli in young, healthy subjects. In nine subjects (23 ± 3 yr), intradermal microdialysis (MD) probes were inserted into the ventral forearm, abdomen, thigh, and lower back and perfused with lactated Ringer solution. RSR over each MD membrane were measured using ventilated capsules with a laser Doppler probe housed in each capsule for measurement of red cell flux (laser Doppler flux, LDF) as an index of SkBF. Subjects completed a whole body heating protocol to 1°C rise in oral temperature and an acetylcholine dose response (ACh 1 × 10−7-0.1 M; mean skin temperature 34°C). Maximal LDF were obtained at the end of both protocols (50 mM sodium nitroprusside).During heating RSR varied among sites ( P < 0.0001) and was greater on the back versus other sites ( P < 0.05), but LDF was similar between sites ( P = 0.343). RSR and SkBF showed a strong relation during initial (arm: r = 0.77 ± 0.09, thigh: r = 0.81 ± 0.08, abdomen: r = 0.89 ± 0.04, back: r = 0.86 ± 0.04) but not latter stages of heating. No differences in RSR ( P = 0.160) or SkBF (LDF, P = 0.841) were observed between sites during ACh perfusion. Taken together, these data suggest that increases in SkBF are necessary to initiate and increase sweating, but further rises in RSR are not fully dependent on SkBF in a dose-response manner. Furthermore, RSR cannot be explained by cholinergic sensitivity or variation in SkBF.


1998 ◽  
Vol 85 (1) ◽  
pp. 175-180 ◽  
Author(s):  
D. L. Kellogg ◽  
S. R. Morris ◽  
S. B. Rodriguez ◽  
Y. Liu ◽  
M. Grossmann ◽  
...  

During dynamic exercise in the heat, increases in skin blood flow are attenuated in hypertensive subjects when compared with normotensive subjects. We studied responses to passive heat stress (water-perfused suits) in eight hypertensive and eight normotensive subjects. Forearm blood flow was measured by venous-occlusion plethysmography, mean arterial pressure (MAP) was measured by Finapres, and forearm vascular conductance (FVC) was calculated. Bretylium tosylate (BT) iontophoresis was used to block active vasoconstriction in a small area of skin. Skin blood flow was indexed by laser-Doppler flowmetry at BT-treated and untreated sites, and cutaneous vascular conductance was calculated. In normothermia, FVC was lower in hypertensive than in normotensive subjects ( P < 0.01). During heat stress, FVC rose to similar levels in both groups ( P > 0.80); concurrent cutaneous vascular conductance increases were unaffected by BT treatment ( P > 0.60). MAP was greater in hypertensive than in normotensive subjects during normothermia ( P < 0.05, hypertensive vs. normotensive subjects). During hyperthermia, MAP fell in hypertensive subjects but showed no statistically significant change in normotensive subjects ( P < 0.05, hypertensive vs. normotensive subjects). The internal temperature at which vasodilation began did not differ between groups ( P> 0.80). FVC is reduced during normothermia in unmedicated hypertensive subjects; however, they respond to passive heat stress in a fashion no different from normotensive subjects.


2001 ◽  
Vol 281 (2) ◽  
pp. R591-R595 ◽  
Author(s):  
Ken Aoki ◽  
Dan P. Stephens ◽  
John M. Johnson

It is not clear whether the diurnal variation in the cutaneous circulatory response to heat stress is via the noradrenergic vasoconstrictor system or the nonadrenergic active vasodilator system. We conducted whole body heating experiments in eight male subjects at 0630 (AM) and 1630 (PM). Skin blood flow was monitored by laser-Doppler flowmetry at control sites and at sites pretreated with bretylium (BT) to block noradrenergic vasoconstriction. Noninvasive blood pressure was used to calculate cutaneous vascular conductance. The sublingual temperature (Tor) threshold for cutaneous vasodilation was significantly higher in PM at control and at BT-treated sites (both P < 0.01), suggesting the diurnal shift in threshold depends on the active vasodilator system. The slope of cutaneous vascular conductance as a percentage of its maximum with respect to Tor was significantly lower in AM at control sites only. Also, in the AM, the slope at control sites was significantly lower than that at BT-treated sites ( P < 0.05), suggesting that the diurnal change in the sensitivity of cutaneous vasodilation depends on vasoconstrictor system function. Overall, the diurnal variation in the reflex control of skin blood flow during heat stress involves both vasoconstrictor and active vasodilator systems.


Healthcare ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 143
Author(s):  
Jun Murata ◽  
Shin Murata ◽  
Takayuki Kodama ◽  
Hideki Nakano ◽  
Masayuki Soma ◽  
...  

We hypothesized that age-related changes in sensory function might be reflected by a modulation of the blood flow response associated with tactile sensation. The aim of the present study was to clarify how the blood flow response of the fingers during concentrated finger perception is affected by aging. We measured the tactile-pressure threshold of the distal palmar pad of the index finger and skin blood flow in the finger (SBF) during Braille reading performed under blind conditions in young (n = 27) and older (n = 37) subjects. As a result, the tactile-pressure threshold was higher in older subjects (2.99 ± 0.37 log10 0.1 mg) than in young subjects (2.76 ± 0.24 log10 0.1 mg) (p < 0.01). On the other hand, the SBF response was markedly smaller in older subjects (−4.9 ± 7.0%) than in young subjects (−25.8 ± 15.4%) (p < 0.01). Moreover, the peak response arrival times to Braille reading in older and young subjects were 12.5 ± 3.1 s and 8.8 ± 3.6 s, respectively (p < 0.01). A decline in tactile sensitivity occurs with aging. Blood flow responses associated with tactile sensation are also affected by aging, as represented by a decrease in blood flow and a delay in the reaction time.


2002 ◽  
Vol 93 (6) ◽  
pp. 1918-1924 ◽  
Author(s):  
Robert Carter ◽  
Thad E. Wilson ◽  
Donald E. Watenpaugh ◽  
Michael L. Smith ◽  
Craig G. Crandall

To identify the effects of exercise recovery mode on cutaneous vascular conductance (CVC) and sweat rate, eight healthy adults performed two 15-min bouts of upright cycle ergometry at 60% of maximal heart rate followed by either inactive or active (loadless pedaling) recovery. An index of CVC was calculated from the ratio of laser-Doppler flux to mean arterial pressure. CVC was then expressed as a percentage of maximum (%max) as determined from local heating. At 3 min postexercise, CVC was greater during active recovery (chest: 40 ± 3, forearm: 48 ± 3%max) compared with during inactive recovery (chest: 21 ± 2, forearm: 25 ± 4%max); all P < 0.05. Moreover, at the same time point sweat rate was greater during active recovery (chest: 0.47 ± 0.10, forearm: 0.46 ± 0.10 mg · cm−2 · min−1) compared with during inactive recovery (chest: 0.28 ± 0.10, forearm: 0.14 ± 0.20 mg · cm−2 · min−1); all P < 0.05. Mean arterial blood pressure, esophageal temperature, and skin temperature were not different between recovery modes. These data suggest that skin blood flow and sweat rate during recovery from exercise may be modulated by nonthermoregulatory mechanisms and that sustained elevations in skin blood flow and sweat rate during mild active recovery may be important for postexertional heat dissipation.


1987 ◽  
Vol 62 (2) ◽  
pp. 606-610 ◽  
Author(s):  
P. G. Snell ◽  
W. H. Martin ◽  
J. C. Buckey ◽  
C. G. Blomqvist

Lower leg blood flow and vascular conductance were studied and related to maximal oxygen uptake in 15 sedentary men (28.5 +/- 1.2 yr, mean +/- SE) and 11 endurance-trained men (30.5 +/- 2.0 yr). Blood flows were obtained at rest and during reactive hyperemia produced by ischemic exercise to fatigue. Vascular conductance was computed from blood flow measured by venous occlusion plethysmography, and mean arterial blood pressure was determined by auscultation of the brachial artery. Resting blood flow and mean arterial pressure were similar in both groups (combined mean, 3.0 ml X min-1 X 100 ml-1 and 88.2 mmHg). After ischemic exercise, blood flows were 29- and 19-fold higher (P less than 0.001) than rest in trained (83.3 +/- 3.8 ml X min-1 X 100 ml-1) and sedentary subjects (61.5 +/- 2.3 ml X min-1 X 100 ml-1), respectively. Blood pressure and heart rate were only slightly elevated in both groups. Maximal vascular conductance was significantly higher (P less than 0.001) in the trained compared with the sedentary subjects. The correlation coefficients for maximal oxygen uptake vs. vascular conductance were 0.81 (trained) and 0.45 (sedentary). These data suggest that physical training increases the capacity for vasodilation in active limbs and also enables the trained individual to utilize a larger fraction of maximal vascular conductance than the sedentary subject.


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