Age alters the cardiovascular response to direct passive heating

Duringdirect passive heating in young men, a dramatic increase in skin bloodflow is achieved by a rise in cardiac output (_c) andredistribution of flow from the splanchnic and renal vascular beds. Toexamine the effect of age on these responses, seven young (Y; 23 ± 1 yr) and seven older (O; 70 ± 3 yr) men were passively heated withwater-perfused suits to their individual limit of thermal tolerance.Measurements included heart rate (HR), _c (byacetylene rebreathing), central venous pressure (via peripherally inserted central catheter), blood pressures (by brachial auscultation), skin blood flow (from increases in forearm blood flow by venous occlusion plethysmography), splanchnic blood flow (by indocyanine green clearance), renal blood flow (byp-aminohippurateclearance), and esophageal and mean skin temperatures._c wassignificantly lower in the older than in the young men (11.1 ± 0.7 and 7.4 ± 0.2 l/min in Y and O, respectively, at the limit ofthermal tolerance; P < 0.05),despite similar increases in esophageal and mean skin temperatures andtime to reach the limit of thermal tolerance. A lower stroke volume (99 ± 7 and 68 ± 4 ml/beat in Y and O, respectively, P < 0.05), most likely due to anattenuated increase in inotropic function during heating, was theprimary factor for the lower _c observed inthe older men. Increases in HR were similar in the young and older men;however, when expressed as a percentage of maximal HR, the older menrelied on a greater proportion of their chronotropic reserve to obtainthe same HR response (62 ± 3 and 75 ± 4% maximal HR in Y andO, respectively, P < 0.05). Furthermore, the older men redistributed less blood flow from thecombined splanchnic and renal circulations at the limit of thermaltolerance (960 ± 80 and 720 ± 100 ml/min in Y and O,respectively, P < 0.05). As a resultof these combined attenuated responses, the older men had asignificantly lower increase in total blood flow directed to the skin.

     

Upper airway muscle activity in normal women: influence of hormonal status

Obstructive sleep apnea is a disorder with astrong male predominance. One possible explanation could be an effectof female hormones on pharyngeal dilator muscle activity. Therefore, we determined the level of awake genioglossus electromyogram (EMGgg) andupper airway resistance in 12 pre- and 12 postmenopausal women underbasal conditions and during the application of an inspiratory resistiveload (25 cmH₂O · l¹ · s).In addition, a subgroup of eight postmenopausal women were studied asecond time after 2 wk of combined estrogen and progesterone replacement in standard doses. Peak phasic and tonic genioglossus activity, expressed as a percentage of maximum, were highest in theluteal phase of the menstrual cycle (phasic 23.9 ± 3.8%, tonic 10.2 ± 1.0%), followed by the follicular phase (phasic 15.5 ± 2.2%, tonic 7.3 ± 0.8%), and were lowest in the postmenopausal group (phasic 11.3 ± 1.6%, tonic of 5.0 ± 0.6), whereas upper airway resistance did not differ. There was a weak but significant positive correlation between progesterone levels and both peak phasic(P < 0.05) and tonic(P < 0.01) EMGgg. Finally, there was a significant increase in EMGgg in the postmenopausal group restudied after hormone therapy. In conclusion, female hormones (possibly progesterone) have a substantial impact on upper airway dilator muscleactivity.

     

Hypercapnic blood pressure response is greater during the luteal phase of the menstrual cycle

Edwards, N., I. Wilcox, O. J. Polo, and C. E. Sullivan.Hypercapnic blood pressure response is greater during the luteal phase of the menstrual cycle. J. Appl.Physiol. 81(5): 2142-2146, 1996.We investigatedthe cardiovascular responses to acute hypercapnia during the menstrualcycle. Eleven female subjects with regular menstrual cycles performedhypercapnic rebreathing tests during the follicular and luteal phasesof their menstrual cycles. Ventilatory and cardiovascular variableswere recorded breath by breath. Serum progesterone and estradiol weremeasured on each occasion. Serum progesterone was higher during theluteal [50.4 ± 9.6 (SE) nmol/l] than during thefollicular phase (2.1 ± 0.7 nmol/l;P < 0.001), but serum estradiol didnot differ (follicular phase, 324 ± 101 pmol/l; luteal phase, 162 ± 71 pmol/l; P = 0.61). Thesystolic blood pressure responses during hypercapnia were 2.0 ± 0.3 and 4.0 ± 0.5 mmHg/Torr (1 Torr = 1 mmHg rise inend-tidal PCO₂) during the follicularand luteal phases, respectively, of the menstrual cycle(P < 0.01). The diastolic bloodpressure responses were 1.1 ± 0.2 and 2.1 ± 0.3 mmHg/Torrduring the follicular and luteal phases, respectively(P < 0.002). Heart rate responses did not differ during the luteal (1.7 ± 0.3 beats ^· min^{1 ·} Torr¹)and follicular phases (1.4 ± 0.3 beats ^· min^{1 ·} Torr¹;P = 0.59). These data demonstrate agreater pressor response during the luteal phase of the menstrual cyclethat may be related to higher serum progesterone concentrations.

     

Cyclooxygenase inhibition potentiates the renal vascular response to endothelin-1 in humans

Vascular endothelin-receptor stimulation resultsin vasoconstriction and concomitant production of the vasodilatorsprostaglandin I₂ and nitric oxide.The vascular effects of cyclooxygenase (COx) blockade (diclofenacintravenously) and the subsequent vasoconstrictor response toendothelin-1 (ET-1) infusion 30 min after diclofenac were studied inhealthy men. With COx blockade, cardiac output (7%) and splanchnic(14%) and renal (12%) blood flows fell (all P < 0.001). Splanchnic blood flowreturned to basal value within 30 min. Mean arterial blood pressureincreased (4%, P < 0.001). Splanchnic glucose output fell (22%,P < 0.01). Subsequent ET-1 infusioncaused, compared with previous ET-1 infusion without COx blockade (G. Ahlborg, E. Weitzberg, and J. M. Lundberg. J. Appl.Physiol. 77: 121-126, 1994; E. Weitzberg, G. Ahlborg, and J. M. Lundberg. Biochem. Biophys. Res.Commun. 180: 1298-1303, 1991; E. Weitzberg, G. Ahlborg, and J. M. Lundberg. Clin.Physiol. (Colch.) 13: 653-662, 1993),the same increase in mean arterial blood pressure (4%), decreases incardiac output (13%) and splanchnic blood flow (38%), but nosignificant change in splanchnic glucose output. Renal blood flowreduction was potentiated (33 ± 3 vs. 23 ± 2%,P < 0.02), with a total reductioncorresponding to 43 ± 3%(P < 0.01 vs. 23 ± 3%). Weconclude that COx inhibition induces renal and splanchnicvasoconstriction. The selectively increased renal vascularresponsiveness to ET-1 emphasizes the importance of endogenousarachidonic acid metabolites (i.e., prostaglandin I₂) to counteract ET-1-mediatedrenal vasoconstriction.

     

Women at altitude: changes in carbohydrate metabolism at 4,300-m elevation and across the menstrual cycle

Wehypothesized that, in women, the blood glucose response to a meal (BGR)would be lower after exposure to 4,300 m compared with sea level (SL)and that BGR would be reduced in the presence of estrogen plusprogesterone (E+P) relative to estrogen alone (E). Sixteenwomen were studied in both the E and E+P conditions at SL and in eitherthe E or E+P condition at 4,300 m. On day 9 in each condition, blood was sampled before, andevery 30 min for 2 h after, the subjects ate a high-carbohydrate meal.At 4,300 m, BGR peaked at a lower value (5.73 ± 0.94 mM) than at SL(6.44 ± 1.45 mM) and returned to baseline more slowly(P < 0.05). Plasma insulin valueswere the same but C peptide was slightly higher at 4,300 m(P < 0.05). At SL, BGR returned tobaseline more slowly in E+P condition (5.13 ± 0.89 and 5.21 ± 0.91 mM at 60 and 90 min, respectively) relative to Econdition (4.51 ± 0.52 and 4.69 ± 0.88 mM, respectively)(P < 0.05). Insulin and C peptidewere not different between E and E+P conditions. The data indicate thatBGR is lower in women at high altitude compared with the SL, possiblydue to greater suppression of hepatic glucose production or stimulationof peripheral glucose uptake by insulin. BGR was lower in E conditionrelative to E+P condition at SL and possibly at 4,300 m, but therelative concentrations of ovarian hormones do not appear to alter themagnitude of the change in BGR when women are exposed to high altitude.

     

Effects of the ovarian cycle on sympathetic neural outflow during static exercise

We comparedreflex responses to static handgrip at 30% maximal voluntarycontraction (MVC) in 10 women (mean age 24.1 ± 1.7 yr) during twophases of their ovarian cycle: the menstrual phase (days 1-4) and the follicularphase (days10-12). Changes in muscle sympathetic nerve activity (MSNA; microneurography) in response tostatic exercise were greater during the menstrual compared withfollicular phase (phase effect P = 0.01). Levels of estrogen were less during the menstrual phase(75 ± 5.5 vs. 116 ± 9.6 pg/ml, days 1-4 vs.days 10-12;P = 0.002). Generated tension did not explain differences in MSNA responses (MVC: 29.3 ± 1.3 vs. 28.2 ± 1.5 kg, days 1-4 vs.days 10-12;P = 0.13). In a group of experiments with the use of ³¹P-NMRspectroscopy, no phase effect was observed forH⁺ andH₂PO₄ concentrations(n = 5). During an ischemicrhythmic handgrip paradigm (20% MVC), a phase effect was notobserved for MSNA or H⁺ orH₂PO₄ concentrations,suggesting that blood flow was necessary for the expression of thecycle-related effect. The present studies suggest that, during statichandgrip exercise, MSNA is increased during the menstrual compared withthe follicular phase of the ovarian cycle.

     

Effects of gender on resting leg blood flow: implications for measurement of regional substrate oxidation

Jensen, Michael D., Tu T. Nguyen, A. HernándezMijares, C. Michael Johnson, and Michael J. Murray. Effects ofgender on resting leg blood flow: implications for measurement ofregional substrate oxidation. J. Appl.Physiol. 84(1): 141-145, 1998.These studies weredesigned to examine whether the respiratory quotient (RQ) of leg tissue(primarily skeletal muscle) would increase to a greater degree in womenthan in men during meal ingestion. We found that mean leg and systemicRQ values were similar in men under both basal and fed conditions,whereas the agreement was poor in women. In women, leg RQ values tendedto be greater than the systemic RQ, whereas splanchnic RQ values tendedto be lower than the systemic RQ. The possibility that measurementimprecision accounted for the different findings in women could not beexcluded because the arteriovenous bloodO₂ differences were almost twice as great in men as in women (53.7 ± 5.4 vs. 28.6 ± 2.9 ml ofO₂/l, respectively;P < 0.01), as were venoarterialblood CO₂ differences. The smallerarteriovenous differences in women appeared to limit our ability toaccurately measure their leg RQ values.O₂ uptake relative to leg fat-freemass (FFM) was not different between men and women, whereas leg bloodflow relative to leg FFM was greater in women than in men (55 ± 3vs. 39 ± 2 ml · kgFFM¹ · min¹,respectively; P < 0.001). Thesefindings were confirmed by examining data from other studies conductedin our laboratory to create a larger data set. We conclude that restingleg blood flow in women is greater (relative to FFM) than in men,making it more difficult to accurately measure leg RQ in women.

     

Measurement of pulmonary blood flow by fractal analysis of flow heterogeneity in isolated canine lungs

Barman, Scott A., Laryssa L. McCloud, John D. Catravas, andIna C. Ehrhart. Measurement of pulmonary blood flow by fractalanalysis of flow heterogeneity in isolated canine lungs. J. Appl. Physiol. 81(5):2039-2045, 1996.Regional heterogeneity of lung blood flow can bemeasured by analyzing the relative dispersion (RD) of mass(weight)-flow data. Numerous studies have shown that pulmonary bloodflow is fractal in nature, a phenomenon that can be characterized bythe fractal dimension and the RD for the smallest realizable volumeelement (piece size). Although information exists for theapplicability of fractal analysis to pulmonary blood flow in wholeanimal models, little is known in isolated organs. Therefore, thepresent study was done to determine the effect of blood flow rate onthe distribution of pulmonary blood flow in the isolated blood-perfusedcanine lung lobe by using fractal analysis. Four different radiolabeledmicrospheres (¹⁴¹Ce,⁹⁵Nb,⁸⁵Sr, and⁵¹Cr), each 15 µm in diameter,were injected into the pulmonary lobar artery of isolated canine lunglobes (n = 5) perfused at fourdifferent flow rates ( flow1 = 0.42 ± 0.02 l/min;flow2 = 1.12 ± 0.07 l/min;flow 3 = 2.25 ± 0.17 l/min; flow 4 = 2.59 ± 0.17 l/min), and the pulmonary blood flow distribution was measured. Theresults of the present study indicate that under isogravimetric bloodflow conditions, all regions of horizontally perfused isolated lunglobes received blood flow that was preferentially distributed to themost distal caudal regions of the lobe. Regional pulmonary blood flowin the isolated perfused canine lobe was heterogeneous and fractal innature, as measured by the RD. As flow rates increased, fractal dimension values (averaging 1.22 ± 0.08) remained constant, whereas RD decreased, reflecting more homogeneous blood flowdistribution. At any given blood flow rate, high-flow areas of the lobereceived a proportionally larger amount of regional flow, suggestingthat the degree of pulmonary vascular recruitment may also be spatially related.

     

Effects of hormone replacement on growth hormone and prolactin exercise responses in postmenopausal women

Kraemer, R. R., L. G. Johnson, R. Haltom, G. R. Kraemer, H. Gaines, M. Drapcho, T. Gimple, and V. Daniel Castracane. Effects of hormone replacement on growth hormone and prolactin exercise responses in postmenopausal women. J. Appl.Physiol. 84(2): 703-708, 1998.Exercise elevatesgrowth hormone (GH) and prolactin (PRL) blood concentrations inpremenopausal women. Postmenopausal women taking hormone replacementtherapy (HRT) maintain higher estrogen levels that could affect GH andPRL. The purpose of the study was to determine the effects of HRT on GHand PRL responses to treadmill exercise. Seventeen healthy women whowere postmenopausal (naturally or surgically) [8 on HRT; 9 not onHRT (NHRT)], completed 30 min of treadmill exercise at 79.16 ± 1.2% maximal O₂ consumption (HRT group) and 80.19 ± 0.91% maximalO₂ consumption (NHRT group). Bloodsamples were collected from an intravenous catheter during an exercisesession and during a control session without exercise. GH and PRLconcentrations were significantly higher in the exercise trial than inthe nonexercise trial, whereas resting concentrations were similar forboth trials. GH and PRL peaked at 10.8 ± 1.60 and 12.67 ± 2.58 ng/ml, respectively, for HRT subjects and at 4.90 ± 1.18 and 9.04 ± 2.17 ng/ml, respectively, for NHRT subjects. GH concentrations inthe exercise trial were significantly higher for HRT than for NHRTsubjects. This is the first study to demonstrate that HRT enhancestreadmill-exercise-induced GH release and that similar PRL responses totreadmill exercise occur in postmenopausal women regardless of HRTstatus.

     

Otolithic and tonic neck receptors control of limb blood flow in humans

Normand, Hervé, Olivier Etard, and Pierre Denise.Otolithic and tonic neck receptors control of limb blood flow in humans. J. Appl. Physiol. 82(6):1734-1738, 1997.The aim of this study was to evaluate the roleof otolithic receptors and neck mechanoreceptors on the control of thecardiovascular system. We measured calf (CBF) and forearm blood flow(FBF) by strain-gauge plethysmography, mean arterial pressure (MAP),and heart rate (HR) in 12 healthy subjects in two body positions (lyingprone and on the left side) and three head positions (reference,flexion, and extension). When the subjects were lying prone, CBF andFBF were lower in head flexion (5.2 ± 0.6 and 3.2 ± 0.4 ml · min¹ · 100 ml¹, respectively) than inreference position (5.8 ± 0.4 and 3.8 ± 0.3 ml · min¹ · 100 ml¹;P < 0.05), with nosignificant difference in MAP and HR. When the subjects were lying onthe side, changing the head position from reference to flexionsignificantly increased FBF (from 3.7 ± 0.2 to. 4.2 ± 0.4 ml · min¹ · 100 ml¹), MAP (from 97.2 ± 3.3 to 102.4 ± 5.8 mmHg), and HR (from 63.7 ± 1.4 to 65.9 ± 2.5 beats/min; P < 0.05). Because otolithic receptors andneck mechanoreceptors are involved when the subjects are lying prone,and otolithic receptors are not involved when the subjects are lying onthe side, the results suggest that otolithic and neck mechanoreceptorsexert significant influences over the cardiovascular system.

     

Sympathetic drive to liver and nonhepatic splanchnic tissue during heavy exercise

Coker, Robert H., Mahesh G. Krishna, D. Brooks Lacy, Eric J. Allen, and David H. Wasserman. Sympathetic drive to liver andnonhepatic splanchnic tissue during heavy exercise. J. Appl. Physiol. 82(4): 1244-1249, 1997.Thecontribution of sympathetic drive and vascular catecholamine deliveryto the splanchnic bed during heavy exercise was studied in dogs thatunderwent a laparotomy during which flow probes were implanted onto theportal vein and hepatic artery and catheters were inserted into thecarotid artery, portal vein, and hepatic vein. At least 16 days aftersurgery, dogs completed a 20-min heavy exercise protocol (mean workrate of 5.7 ± 1 miles/h, 20 ± 2% grade). Arterial epinephrine(Epi) and norepinephrine (NE) increased by ~500 and ~900 pg/ml,respectively, after 20 min of heavy exercise. Because Epi is notreleased from the splanchnic bed and because Epi fractional extraction(FX) = NE FX, NE uptake by splanchnic tissue can be calculated despite simultaneous release of NE. Basal nonhepatic splanchnic (NHS) FXincreased from a basal rate of 0.52 ± 0.09 to a peak of 0.64 ± 0.05 at 10 min of exercise. Hepatic Epi FX increased froma basal rate of 0.68 ± 0.10 to 0.81 ± 0.09 at 20 min of exercise. Even though NHS extraction of Epi reduced portal veinEpi levels by ~60%, the release of NE from NHS tissue maintainedportal vein NE at levels similar to those in arterial blood. NHS NEspillover increased from a basal rate of 5.7 ± 1.4 to 11.7 ± 2.8 ng · kg¹ · min¹at 20 min of exercise. Hepatic NE spillover increased from a basal rateof 5.0 ± 1.2 ng · kg¹ · min¹to a peak of 14.2 ± 2.8 ng · kg¹ · min¹at 15 min of exercise. These results show that1) approximately two- and threefoldincreases in NHS and hepatic NE spillover occur during heavy exercise,demonstrating that sympathetic drive to these tissues contributes tothe increase in circulating NE; 2) the high catecholamine FX by the NHS tissues results in an Epi level atthe liver that is considerably lower than that in the arterial blood;and 3) circulating NE delivery tothe liver is sustained despite high catecholamine FX due tosimultaneous NHS NE release.

     

Nitric oxide-endothelin-1 interaction in humans

Ahlborg, Gunvor, and Jan M. Lundberg. Nitricoxide-endothelin-1 interaction in humans. J. Appl.Physiol. 82(5): 1593-1600, 1997.Healthy menreceived N^G-monomethyl-L-arginine(L-NMMA) intravenously to studycardiovascular and metabolic effects of nitric oxide synthase blockadeand whether this alters the response to endothelin-1 (ET-1) infusion.Controls only received ET-1.L-NMMA effects were that heartrate (17%), cardiac output (17%), and splanchnic and renal blood flow(both 33%) fell promptly (all P < 0.01). Mean arterial blood pressure (6%), and systemic (28%) andpulmonary (40%) vascular resistances increased(P < 0.05 to 0.001). Arterial ET-1levels (21%) increased due to a pulmonary net ET-1 release(P < 0.05 to 0.01). Splanchnic glucose output (SGO) fell (26%, P < 0.01). Arterial insulin and glucagon were unchanged. Subsequent ET-1infusion caused no change in mean arterial pressure, heart rate, orcardiac output, as found in the present controls, or in splanchnic andrenal blood flow or splanchnic glucose output as previously found withET-1 infusion (G. Ahlborg, E. Weitzberg, and J. M. Lundberg.J. Appl. Physiol. 79: 141-145,1995). In conclusion, L-NMMAlike ET-1, induces prolonged cardiovascular effects and suppresses SGO.L-NMMA causes pulmonary ET-1release and blocks responses to ET-1 infusion. The results indicatethat nitric oxide inhibits ET-1 production and thereby interacts withET-1 regarding increase in vascular tone and reduction of SGO inhumans.

     

Fuel metabolism in men and women during and after long-duration exercise

This study aimed to determine gender-baseddifferences in fuel metabolism in response to long-duration exercise.Fuel oxidation and the metabolic response to exercise were compared inmen (n = 14) and women(n = 13) during 2 h (40% of maximalO₂ uptake) of cycling and 2 h ofpostexercise recovery. In addition, subjects completed a separatecontrol day on which no exercise was performed. Fuel oxidation wasmeasured using indirect calorimetry, and blood samples were drawn forthe determination of circulating substrate and hormone levels. Duringexercise, women derived proportionally more of the total energyexpended from fat oxidation (50.9 ± 1.8 and 43.7 ± 2.1% forwomen and men, respectively, P < 0.02), whereas men derived proportionally more energy from carbohydrateoxidation (53.1 ± 2.1 and 45.7 ± 1.8% for men and women,respectively, P < 0.01). Thesegender-based differences were not observed before exercise, afterexercise, or on the control day. Epinephrine(P < 0.007) and norepinephrine(P < 0.0009) levels weresignificantly greater during exercise in men than in women (peakepinephrine concentrations: 208 ± 36 and 121 ± 15 pg/ml in menand women, respectively; peak norepinephrine concentrations: 924 ± 125 and 659 ± 68 pg/ml in men and women, respectively). Ascirculating glycerol levels were not different between the two groups,this suggests that women may be more sensitive to the lipolytic action of the catecholamines. In conclusion, these data support the view thatdifferent priorities are placed on lipid and carbohydrate oxidationduring exercise in men and women and that these gender-based differences extend to the catecholamine response to exercise.

     

Blood pressure risk factors in healthy postmenopausal women: physical activity and hormone replacement

Stevenson, Edith T., Kevin P. Davy, Pamela P. Jones,Christopher A. Desouza, and Douglas R. Seals. Blood pressure risk factors in healthy postmenopausal women: physical activity and hormonereplacement. J. Appl. Physiol. 82(2):652-660, 1997.The prevalence of cardiovascular disease (CVD)increases with advancing age in women, particularly after menopause.CVD risk is lower in physically active women relative to theirsedentary peers, but the responsible mechanisms are not wellunderstood. The aims of this study were to test the hypotheses that1) physically active postmenopausalwomen demonstrate more favorable blood pressure (BP)-related riskfactors for CVD than do sedentary healthy women and2) women on hormone replacementtherapy (HRT) also have more favorable levels of these CVD riskfactors. BP-related CVD risk factors were measured in physically activewomen (n = 18; age 55 ± 1 yr;n = 8 on HRT) and in healthyless-active controls (n = 34; age 59 ± 1 yr; n = 17 on HRT). Maximaloxygen consumption was higher in the active group, whereas waist-to-hipratio and waist circumference were lower (allP < 0.005). The activewomen demonstrated marginally lower (5-8 mmHg;P  0.10) levels of casual, 24-h, anddaytime systolic BP (SBP). They also tended to have lower(P = 0.11) daytime SBP loads(percentage of BP recordings >140/90 mmHg) and lower daytime andnighttime BP variabilities (P = 0.04)and a reduced (P < 0.007) SBPresponse to submaximal exercise. Women on HRT tended to have lower(3-4 mmHg; P = 0.07) levels of24-h and nighttime diastolic BP (DBP) relative to the nonusers andsmaller (P < 0.04) daytime and 24-hDBP loads. Stepwise multiple regression indicated that waistcircumference was the primary predictor of most of the SBP-related CVDrisk factors while HRT use was the best predictor for DBP loads. Thesefindings indicate that, in general, physically active postmenopausalwomen demonstrate more favorable SBP-related CVD risk factors relative to their less-active healthy peers, which may be mediated, in part, bytheir lower levels of abdominal adiposity. In addition, HRT use tendsto be associated with lower levels of DBP-related CVD risk factors.

     

Pulmonary blood flow distribution has a hilar-to-peripheral gradient in awake, prone sheep

Walther, Sten M., Karen B. Domino, Robb W. Glenny, Nayak L. Polissar, and Michael P. Hlastala. Pulmonary blood flow distribution has a hilar-to-peripheral gradient in awake, prone sheep.J. Appl. Physiol. 82(2): 678-685, 1997.We examined the pulmonary blood flow distribution withintravenous fluorescent microspheres (15 µm) in nine prone,unanesthetized, lambs. Lungs flushed free of blood were air-dried attotal lung capacity and sectioned into~2-cm³ pieces. The pieces wereweighed, identified by lobe, and assigned spatial coordinates.Fluorescence was read on a spectrophotometer, and signals werecorrected for piece weight and normalized to mean flow. Pulmonary bloodflow heterogeneity was assessed by using the coefficient of variationof the flow data. The number of pieces (±SD) analyzed were 1,249 ± 150/animal. Heterogeneity of blood flow was 29.5 ± 6.5%(coefficient of variation = SD/mean). Pulmonary blood flow decreasedwith distance from hilus (P < 0.002) but did not change significantly with vertical height. Distance fromthe hilus was the best predictor of pulmonary blood flow (R² = 0.201) and,together with spatial coordinates and lobe, accounted for 33.7 ± 12.0% of blood flow variability. We conclude that pulmonary blood flowin the awake, prone sheep is distributed with a hilar-to-peripheral gradient but no significant vertical gradient.

     

Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women

Brooks, E. M., A. L. Morgan, J. M. Pierzga, S. L. Wladkowski, J. T. O'Gorman, J. A. Derr, and W. L. Kenney. Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women. J. Appl.Physiol. 83(2): 477-484, 1997.This investigationexamined effects of chronic (2 yr) hormone replacement therapy (HRT),both estrogen replacement therapy (ERT) and estrogen plus progesteronetherapy (E+P), on core temperature and skin blood flow responses ofpostmenopausal women. Twenty-five postmenopausal women [9 not onHRT (NO), 8 on ERT, 8 on E+P] exercised on a cycle ergometer for1 h at an ambient temperature of 36°C. Cutaneous vascularconductance (CVC) was monitored by laser-Doppler flowmetry, and forearmvascular conductance (FVC) was measured by using venous occlusionplethysmography. Iontophoresis of bretylium tosylate was performedbefore exercise to block local vasoconstrictor (VC) activity at oneskin site on the forearm. Rectal temperature (T_re) was ~0.5°C lower forthe ERT group (P < 0.01) comparedwith E+P and NO groups at rest and throughout exercise. FVC: mean body temperature (T_b) and CVC:T_b curves were shifted~0.5°C leftward for the ERT group(P < 0.0001). Baseline CVC wassignificantly higher in the ERT group(P < 0.05), but there was nointeraction between bretylium treatment and groups once exercise wasinitiated. These results suggest that1) chronic ERT likely acts centrally to decrease T_re,2) ERT lowers theT_re at which heat-loss effector mechanisms are initiated, primarily by actions on active cutaneous vasodilation, and 3) addition ofexogenous progestins in HRT effectively blocks these effects.

     

Genome and Hormones: Gender Differences in Physiology: Selected Contribution: Gender differences in the endothelin-B receptor contribution to basal cutaneous vascular tone in humans

To testwhether the contribution of endothelin-B (ET-B) receptors to restingvascular tone differs between genders, we administered the ET-Breceptor antagonist BQ-788 into the forearm skin of 11 male and 11 female subjects by intradermal microdialysis. Skin blood flow wasmeasured using laser-Doppler flowmetry at the microdialysis site. Theprobe was perfused with Ringer solution alone, followed by BQ-788 (150 nM) and finally sodium nitroprusside (28 mM) to effect maximalcutaneous vasodilation. Cutaneous vascular conductance (CVC) wascalculated (laser-Doppler flowmetry/mean arterial pressure) andnormalized to maximal levels (%max). In male subjects, baseline CVCwas (mean ± SE) 19 ± 3%max and increased to 26 ± 5%max with BQ-788 (P < 0.05 vs. baseline). In femalesubjects, baseline CVC was 13 ± 1%max and decreased to 10 ± 1%max in response to BQ-788. CVC responses to BQ-788 differed withgender (P < 0.05); thus the contribution of ET-Breceptors to resting cutaneous vascular tone differs between men andwomen. In men, ET-B receptors mediate tonic vasoconstriction, whereas,in women, ET-B receptors mediate tonic vasodilation.

     

Importance of airway blood flow on particle clearance from the lung

Wagner, Elizabeth M., and W. Michael Foster. Importanceof airway blood flow on particle clearance from the lung.J. Appl. Physiol. 81(5):1878-1883, 1996.The role of the airway circulation insupporting mucociliary function has been essentially unstudied. Weevaluated the airway clearance of inert, insoluble particles inanesthetized ventilated sheep (n = 8),in which bronchial perfusion was controlled, to determine whetherairway mucosal blood flow is essential for maintaining surfacetransport of particles through airways. The bronchial branch of thebronchoesophageal artery was cannulated and perfused with autologousblood at control flow (0.6 ml ^· min^{1 ·} kg¹)or perfusion was stopped. With the sheep in a supine position and aftera steady-state ¹³³Xe ventilationscan for designation of lung zones of interest, an inert^99mTc-labeled sulfur colloidaerosol (2.1-µm diameter) was deposited in the lung. The clearancekinetics of the radiolabeled particles were determined from theactivity-time data obtained for right and left lung zones. At 60 minpostdeposition of aerosol, average airway particle retention forcontrol bronchial blood flow conditions was 57 ± 7 (SE)% for theright and 53 ± 8% for the left lung zones. Clearance of particleswas significantly impaired when bronchial blood flow was stopped, e.g.,right and left lung zones averaged 77 ± 6 and 76 ± 7% at 60 min, respectively (P < 0.05). Thesedata demonstrate a significant influence of the bronchial circulation on mucociliary transport of insoluble particles. Potential mechanisms that may account for these results include the importance of the bronchial circulation for nutrient flow, maintenance of airway walltemperature and humidity, and release of mediators and sequelae associated with tissue ischemia.

     

Inhibition of nitric oxide synthase slows heart rate recovery from cholinergic activation

The role ofnitric oxide (NO) in the cholinergic regulation of heart rate(HR) recovery from an aspect of simulated exercise wasinvestigated in atria isolated from guinea pig to test the hypothesisthat NO may be involved in the cholinergic antagonism of the positivechronotropic response to adrenergic stimulation. Inhibition of NOsynthesis withN^G-monomethyl-L-arginine(L-NMMA, 100 µM) significantlyslowed the time course of the reduction in HR without affecting themagnitude of the response elicited by bath-applied ACh (100 nM) orvagal nerve stimulation (2 Hz). The half-times(t_1/2) of responses were 3.99 ± 0.41 s in control vs. 7.49 ± 0.68 s inL-NMMA(P < 0.05). This was dependent onprior adrenergic stimulation (norepinephrine, 1 µM). The effect ofL-NMMA was reversed byL-arginine (1 mM; t_1/2 4.62 ± 0.39 s). The calcium-channelantagonist nifedipine (0.2 µM) also slowed the kinetics of thereduction in HR caused by vagal nerve stimulation. However, thet_1/2 for the reduction in HR with antagonists (2 mM Cs⁺ and 1 µM ZD-7288) of thehyperpolarization-activated current were significantlyfaster compared with control. There was no additional effect ofL-NMMA orL-NMMA+L-arginineon vagal stimulation in groups treated with nifedipine,Cs⁺, or ZD-7288. Weconclude that NO contributes to the cholinergic antagonism of thepositive cardiac chronotropic effects of adrenergic stimulation byaccelerating the HR response to vagal stimulation. This may involve aninterplay between two pacemaking currents (L-type calcium channelcurrent and hyperpolarization-activated current). Whether NO modulatesthe vagal control of HR recovery from actual exercise remains to bedetermined.

     

Effects of nitric oxide synthase inhibition on cutaneous vasodilation during body heating in humans

We sought toexamine further the potential role of nitric oxide (NO) in the neurallymediated cutaneous vasodilation in nonacral skin during body heating inhumans. Six subjects were heated with a water-perfused suit whilecutaneous blood flow was measured by using laser-Doppler flowmetersplaced on both forearms. The NO synthase inhibitorN^G-monomethyl-L-arginine(L-NMMA) was given selectivelyto one forearm via a brachial artery catheter after marked cutaneousvasodilation had been established. During body heating, oraltemperature increased by 1.1 ± 0.1°C while heart rate increasedby 30 ± 6 beats/min. Mean arterial pressure stayed constant at 84 ± 2 mmHg. In the experimental forearm, cutaneous vascularconductance (CVC; laser-Doppler) decreased to 86 ± 5% of the peakresponse to heating (P < 0.05 vs.pre-L-NMMA values) afterL-NMMA infusion. In somesubjects, L-NMMA caused CVC tofall by ~30%; in others, it had little impact on the cutaneouscirculation. CVC in the control arm showed a similar increase withheating, then stayed constant whileL-NMMA was given to thecontralateral side. These results demonstrate that NO contributesmodestly, but not consistently, to cutaneous vasodilation during bodyheating in humans. They also indicate that NO is not the only factorresponsible for the dilation.