Interaction between nitric oxide signaling and gap junctions: effects on vascular function.

Nitric oxide signaling, through eNOS (or possibly nNOS), and gap junction communication are essential for normal vascular function. While each component controls specific aspects of vascular function, there is substantial evidence for cross-talk between nitric oxide signaling and the gap junction proteins (connexins), and more recently, protein-protein association between eNOS and connexins. This review will examine the evidence for interaction between these pathways in normal and diseased arteries, highlight the questions that remain about the mechanisms of their interaction, and explore the possible interaction between nitric oxide signaling and the newly discovered pannexin channels. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.

Rat small mesenteric artery function after hindlimb suspension.

To determine whether simulated microgravity in rats is associated with vascular dysfunction, we measured responses of isolated, pressurized mesenteric resistance artery segments (157- to 388-microm ID) to vasoconstrictors, pressure, and shear stress after 28-day hindlimb suspension (HS). Results indicated no differences between HS and control (C) groups in 1) sensitivity or maximal responses to vasoconstrictors (norepinephrine, phenylephrine, serotonin, KCl); 2) ID, external diameter, or ratio of wall thickness to ID; 3) distensibility; or 4) vasodilatory responses to shear stress. Myogenic tone was attenuated (P < 0.05) in HS arteries vs. C, as evidenced by 1) decreased magnitude of tone in larger vessels (second-order branch off superior mesenteric artery, 261- to 388-microm ID) at pressures >/=40 mmHg in the presence of phenylephrine (10(-7) M) and 2) decreased magnitude of tone in smaller vessels (third-order branch off superior mesenteric artery, 157- to 277-microm ID), which exhibited spontaneous tone, at pressures > or =70 mmHg. This attenuation of myogenic tone after HS could contribute to orthostatic intolerance because myogenic tone contributes to the overall tone of resistance arteries.

Heat acclimation does not alter rat mesenteric artery response to norepinephrine.

Previous studies have shown that heat acclimation raises the temperature threshold for heat-induced splanchnic vasoconstriction in the rat (W. Haddad and M. Horowitz. Thermal Balance in Health and Disease, Advances in Pharmacological Sciences. Basel: Birkhauser, 1994, p. 203-208; M. Shochina, W. Haddad, U. Meiri, and M. Horo-witz. J. Therm. Biol. 21: 289-295, 1996). We tested the hypothesis that heat acclimation alters splanchnic resistance artery sensitivity to norepinephrine (NE). Male Sprague-Dawley rats (n = 5) were acclimated to 35 degreesC ambient temperature for 5-8 wk. Control rats (n = 5) were maintained at 22-23 degreesC ambient temperature for 5-7 wk. Small mesenteric artery segments (2- to 3-mm length, 100- to 340-micrometer ID) were isolated, cannulated at both ends, and pressurized to 50 mmHg. Artery luminal diameter was measured in response to cumulative doses of NE (10(-9) to 10(-5) M) by using video microscopy. NE dose response was measured at 37 and 43 degreesC bath temperatures. There were no differences in constriction responses to NE between acclimated and control rat arteries at either 37 or 43 degreesC. We conclude that acclimation does not alter rat mesenteric artery sensitivity to NE.

Leucocytosis, thrombocytosis, and plasma osmolality during rest and exercise: an hypothesis.

The mechanism for inducing leucocytosis (increase in white blood cells) and thrombocytosis (increase in platelets) during exercise is unclear. Because plasma osmolality (Osm) may influence T-cell proliferation, Osm and the number of leucocytes (WBC) and platelets in blood were measured periodically during a 90 min rest period, and were compared with those during upright sitting ergometer exercise in six untrained, healthy men who cycled for 70 min at 71% of their maximal oxygen uptake (VO2max). There were 6 experiments in which the subjects drank different fluid formulations (10 ml x kg(-1) of various ionic and osmotic concentrations intermittently during 60 min of the rest period and during the exercise period. Osmolality, and WBC and platelet counts increased significantly (p < 0.05) within the first 10 min of exercise, but the additional 60 min of exercise did not significantly change the leucocytosis or thrombocytosis. There were low but significant correlations between individual values of total WBC and total Osm during exercise (r0.001(2),284 = 0.39) and during rest plus exercise (r0.001(2),499 = 0.43). With combined data from the six experiments, mean Osm correlated highly and significantly with both mean WBC (r0.001(2),6 = 0.95, p < 0.001) and mean platelets (r0.001(2),6 = 0.94, p < 0.01) during the exercise phase. These data indicate that increases in leucocytes, thrombocytes, and osmolality occur primarily within the first 10 min of high-intensity exercise, but neither hypovolemia nor hyperthermia during exercise contributed to the leucocytosis, thrombocytosis, or hyperosmolality. The high correlations between plasma Osm and WBC or platelet counts suggest changes in osmolality may contribute to the mechanism of leucocytosis and thrombocytosis induced by exercise.

Hypervolemia in men from fluid ingestion at rest and during exercise.

BACKGROUND: Plasma osmolality (Osm) is important for controlling and maintaining plasma volume (PV) and body water. The effect of oral rehydration fluids for ameliorating dehydration is well-established; but optimal composition and Osm of fluids for hyperhydrating normally hydrated subjects is less clear. METHODS: Six treatments were used without and with oral fluids of varying ionic and constituent concentrations for hyperhydrating six previously euhydrated men (30 +/- SD 8 yr, 76.84 +/- 16.19 kg, 73 +/- 12 ml.kg-1 PV, 40 +/- 10 ml.min-1.kg-1 peak VO2) sitting at rest for 90 min (VO2 = 0.39 +/- SE 0.02 L.min-1) and during subsequent 70 min of submaximal exercise (VO2 = 2.08 +/- SE 0.33 L.min-1, 70 +/- 7% peak VO2). The hypothesis was that the fluid composition is more important than plasma Osm for increasing PV in euhydrated subjects at rest and maintaining it during exercise. Drink formulation compositions, given at 10 ml.kg-1 body wt, (mean = 768 ml), for the sitting period were: Performance 1 (P1; 55 mEq Na+, 365 mOsm.kg H2O-1), P2 (97 mEq Na+, 791 mOsm.kg-1), P2G (113 mEq Na+, 4% glycerol, 1382 mOsm.kg-1), AstroAde (AA; 164 mEq Na+, 253 mOsm.kg-1), and 01 and 02 (no drinking). The exercise drink (10 ml.kg-1, 768 ml) was P1 for all treatments except 02 (no drinking); thus, drink designations were: P1/P1, P2/P1, P2G/P1, AA/P1, 0/P1, and 0/0. RESULTS: PV at rest increased (p < 0.05) by 4.7% with P1 and by 7.9% with AA. Percent change in PV during exercise was +1% to +3% (NS) with AA/P1; -6% to 0% (NS) with P1/P1, P2/P1, P2G/P1, and 0/P1; and -8% to -5% (p < 0.05) with 0/0. AA, with the lowest Osm of 253 mOsm.kg-1, increased PV at rest (as did P1) and maintained it during exercise, whereas the other drinks with lower Na+ and higher Osm of 365-1382 mOsm.kg-1 did not. CONCLUSION: Drink composition appears to be more important than its Osm for increasing PV at rest and for maintaining it during exercise in previously euhydrated subjects.

Pre-exercise hypervolemia and cycle ergometer endurance in men.

Time to exhaustion at 87-91% of peak VO2 was measured in 5 untrained men (age: 31 +/- 8 years, body mass: 74.20 +/- 16.50 kg, body surface area: 1.90 +/- 0.24 m2, peak VO2: 2.87 +/- 0.40 l min-1, plasma volume: 3.21 +/- 0.88 l; means +/-SD) after consuming nothing (N) or two fluid formulations (10 ml kg-1, 743 +/- 161 ml): Performance 1 (P1), a multi-ionic carbohydrate drink, containing 55 mEq l-1 Na+, 4.16 g l-1 citrate, 20.49 g l-1 glucose, and 365 mOsm kg-1 H2O, and AstroAde (AA), a sodium chloride-sodium citrate hyperhydration drink, containing 164 mEq l-1 Na+, 8.54 g l-1 citrate, <5 mg l-1 glucose, and 253 mOsm kg-1 H2O. Mean (+/-SE) endurance for N, P1 and AA was 24.68 +/- 1.50, 24.55 +/- 1.09, and 30.50 +/- 3.44 min respectively. Percent changes in plasma volume (PV) from -105 min of rest to zero min before exercise were -1.5 +/- 3.2% (N), 0.2 +/- 2.2% (P1), and 4.8 +/- 3.0% (AA; P < 0.05). The attenuated endurance for N and P1 could not be attributed to differences in exercise metabolism (VE, RE, VO2) from the carbohydrate or citrate, terminal heart rate, levels of perceived exertion, forehead or thigh skin blood flow velocity, changes or absolute termination levels of rectal temperature. Thus, the higher level of resting PV for AA just before exercise, as well as greater acid buffering and possible increased energy substrate from citrate, may have contributed to the greater endurance.

Exercise thermoregulation after 6 h of chair rest, 6 degrees head-down bed-rest, and water immersion deconditioning in men.

The purpose was to investigate the mechanism for the excessive exercise hyperthermia following deconditioning (reduction of physical fitness). Rectal (Tre) and mean skin (Tsk) temperatures and thermoregulatory responses were measured in six men [mean (SD) age, 32 (6) years; mass, 78.26 (5.80) kg; surface area, 1.95 (0.11) m2; maximum oxygen uptake (VO2max), 48 (6) ml.min-1.kg-1; whilst supine in air at dry bulb temperature 23.2 (0.6) degree C, relative humidity 31.1 (11.1)% and air speed 5.6 (0.1) m.min-1] during 70 min of leg cycle exercise [51 (4)% VO2max] in ambulatory control (AC), or following 6 h of chair rest (CR), 6 degree head-down bed rest (BR), and 20 degree (WI20) and 80 degree (WI80) foot-down water immersion [water temperature, 35.0 (0.1) degree C]. Compared with the AC exercise delta Tre [mean (SD) 0.77 (0.13) degree C (*P < 0.05), after WI80 0.96 (0.13) degree C*, and after WI20 1.03 (0.09) degree C*. All Tsk responded similarly to exercise: they decreased (NS) by 0.5-0.7 degree C in minutes 4-8 and equilibrated at +0.1 to +0.5 degree C at 60-70. Skin heat conductance was not different among the five conditions (range = 147-159 kJ.m-2.h-1.degree C-1). Results from an intercorrelation matrix suggested that total body sweat rate was more closely related to Tre at 70 min (Tre70) than limb sweat rate or blood flow. Only 36% of the variability in Tre70 could be accounted for by total sweating, and less than 10% from total body dehydration. It would appear that multiple factors are involved which may include change in sensitivity of thermo- and osmoreceptors.

Cycle-powered short radius (1.9M) centrifuge: exercise vs. passive acceleration.

NASA: A human-powered short-arm centrifuge is described. This centrifuge could be used during spaceflight to provide +Gz acceleration while subjects performed exercise, thus supplying two forms of weightlessness countermeasures. Results from a study of cardiovascular responses while using the centrifuge are presented.^ieng