Alpha-adrenergic vascular responsiveness to sympathetic nerve activity is intact after head-down bed rest in humans

Space-flight and its ground-based simulation model, 6 degrees head-down bed rest (HDBR), cause cardiovascular deconditioning in humans. Because sympathetic vasoconstriction plays a very important role in circulation, we examined whether HDBR impairs alpha-adrenergic vascular responsiveness to sympathetic nerve activity. We subjected eight healthy volunteers to 14 days of HDBR and before and after HDBR measured calf muscle sympathetic nerve activity (MSNA; microneurography) and calf blood flow (venous occlusion plethysmography) during sympathoexcitatory stimulation (rhythmic handgrip exercise). HDBR did not change the increase in total MSNA (P = 0.97) or the decrease in calf vascular conductance (P = 0.32) during exercise, but it did augment the increase in calf vascular resistance (P = 0.0011). HDBR augmented the transduction gain from total MSNA into calf vascular resistance, assessed as the least squares linear regression slope of vascular resistance on total MSNA (0.05 +/- 0.02 before HDBR, 0.20 +/- 0.06 U.min-1.burst-1 after HDBR, P = 0.0075), but did not change the transduction gain into calf vascular conductance (P = 0.41). Our data indicate that alpha-adrenergic vascular responsiveness to sympathetic nerve activity is preserved in the supine position after HDBR in humans.     

Local vascular responses affecting blood flow in postural tachycardia syndrome

Postural tachycardia syndrome (POTS) is defined by orthostatic intolerance associated with abnormal upright tachycardia. Some patients have defective peripheral vasoconstriction and increased calf blood flow. Others have increased peripheral arterial resistance and decreased blood flow. In 14 POTS patients (13-19 yr) evenly subdivided among low-flow POTS (LFP) and high-flow POTS (HFP) we tested the hypothesis that myogenic, venoarteriolar, and reactive hyperemic responses are abnormal. We used venous occlusion plethysmography to measure calf venous pressure and blood flow in the supine position and when the calf was lowered by 40 cm to evoke myogenic and venoarteriolar responses and during venous hypertension by 40-mmHg occlusion to evoke the venoarteriolar response. We measured calf reactive hyperemia with plethysmography and cutaneous laser-Doppler flowmetry. Baseline blood flow in LFP was reduced compared with HFP and control subjects (0.8 +/- 0.2 vs. 4.4 +/- 0.5 and 2.7 +/- 0.4 ml.min-1.100 ml-1) but increased during leg lowering (1.2 +/- 0.5 ml.min-1. 100 ml-1) while decreasing in the others. Baseline peripheral arterial resistance was increased in LFP and decreased in HFP compared with control subjects (39 +/- 13 vs. 15 +/- 3 and 22 +/- 5 mmHg.ml-1. 100 ml. min) but decreased to 29 +/- 13 mmHg.ml-1.100 ml. min in LFP during venous hypertension. Resistance increased in the other groups. Maximum calf hyperemic flow and cutaneous flow were similar in all subjects. The duration of hyperemic blood flow was curtailed in LFP compared with either control or HFP subjects (plethysmographic time constant = 20 +/- 2 vs. 29 +/- 4 and 28 +/- 4 s; cutaneous time constant = 60 +/- 25 vs. 149 +/- 53 s in controls). Local blood flow regulation in low-flow POTS is impaired.     

Blood flow to contracting human muscles: influence of increased sympathetic activity

The purpose of this study was to examine the effects of the increased sympathetic activity elicited by the upright posture on blood flow to exercising human forearm muscles. Six subjects performed light and heavy rhythmic forearm exercise. Trials were conducted with the subjects supine and standing. Forearm blood flow (FBF, plethysmography) and skin blood flow (laser Doppler) were measured during brief pauses in the contractions. Arterial blood pressure and heart rate were also measured. During the first 6 min of light exercise, blood flow was similar in the supine and standing positions (approximately 15 ml.min-1.100 ml-1); from minutes 7 to 20 FBF was approximately 3-7 ml.min-1.100 ml-1 less in the standing position (P less than 0.05). When 5 min of heavy exercise immediately followed the light exercise, FBF was approximately 30-35 ml.min-1.100 ml-1 in the supine position. These values were approximately 8-12 ml.min-1.100 ml-1 greater than those observed in the upright position (P less than 0.05). When light exercise did not precede 8 min of heavy exercise, the blood flow at the end of minute 1 was similar in the supine and standing positions but was approximately 6-9 ml.min-1.100 ml-1 lower in the standing position during minutes 2-8. Heart rate was always approximately 10-20 beats higher in the upright position (P less than 0.05). Forearm skin blood flow and mean arterial pressure were similar in the two positions, indicating that the changes in FBF resulted from differences in the caliber of the resistance vessels in the forearm muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modification of the cutaneous vascular response to exercise by local skin temperature

This study examined how local forearm temperature (Tloc) affects the responsiveness of the cutaneous vasculature to a reflex drive for vasoconstriction. We observed responses in forearm blood flow (FBF) and arterial blood pressure to a 5-min bout of supine leg exercise of moderate intensity (125-175 W) after the forearm had been locally warmed to 36, 38, 40, or 42 degrees C for 48 min. With exercise, FBF fell by 1.82 +/- 0.23, 4.06 +/- 0.58, and 3.64 +/- 1.48 ml X 100 ml-1 X min-1 at 36, 38, and 40 degrees C, respectively, and rose by 2.16 +/- 0.57 ml X 100 ml X min-1 at a Tloc of 42 degrees C (mean +/- SE). Forearm vascular conductance (FVC) fell with the onset of exercise by averages of 2.77 +/- 0.57, 7.02 +/- 0.51, 5.36 +/- 0.85, and 4.17 +/- 0.79 ml X 100 ml-1 X min-1 X 100 mmHg-1 at 36, 38, 40, and 42 degrees C, respectively. Second-order polynomial regression analysis indicated that the reductions in FVC were greatest near a Tloc of 39 degrees C and that at a Tloc of 40 or 42 degrees C the cutaneous vasoconstrictor response to the onset of exercise is attenuated. Although elevated Tloc can be used to increase base-line FBF levels to make cutaneous vasoconstrictor responses more obvious, the direct effects of Tloc on this response must also be considered. We conclude that the optimum Tloc for observing reflex cutaneous vasoconstriction is near 39 degrees C.     

Local vasoconstriction in spinal cord-injured and able-bodied individuals.

Local vasoconstriction plays an important role in maintaining blood pressure in spinal cord-injured individuals (SCI). We aimed to unravel the mechanisms of local vasoconstriction [venoarteriolar reflex (VAR) and myogenic response] using both limb dependency and cuff inflation in SCI and compare these with control subjects. Limb blood flow was measured in 11 male SCI (age: 24-55 yr old) and 9 male controls (age: 23-56 yr old) using venous occlusion plethysmography in forearm and calf during three levels of 1) limb dependency, and 2) cuff inflation. During limb dependency, vasoconstriction relies on both the VAR and the myogenic response. During cuff inflation, the decrease in blood flow is caused by the VAR and by a decrease in arteriovenous pressure difference, whereas the myogenic response does not play a role. At the highest level of leg dependency, the percent increase in calf vascular resistance (mean arterial pressure/calf blood flow) was more pronounced in SCI than in controls (SCI 186 +/- 53%; controls 51 +/- 17%; P = 0.032). In contrast, during cuff inflation, no differences were found between SCI and controls (SCI 17 +/- 17%; controls 14 +/- 10%). Percent changes in forearm vascular resistance in response to either forearm dependency or forearm cuff inflation were equal in both groups. Thus local vasoconstriction during dependency of the paralyzed leg in SCI is enhanced. The contribution of the VAR to local vasoconstriction does not differ between the groups, since no differences between groups existed for cuff inflation. Therefore, the augmented local vasoconstriction in SCI during leg dependency relies, most likely, on the myogenic response.     

Reflex vascular defects in the orthostatic tachycardia syndrome of adolescents.

Dependent pooling occurs in postural orthostatic tachycardia syndrome (POTS) related to defective vasoconstriction. Increased venous pressure (Pv) >20 mmHg occurs in some patients (high Pv) but not others (normal Pv). We compared 22 patients, aged 12-18 yr, with 13 normal controls. Continuous blood pressure and strain-gauge plethysmography were used to measure supine forearm and calf blood flow, resistance, venous compliance, and microvascular filtration, and blood flow and swelling during 70 degrees head-up tilt. Supine, high Pv had normal resistance in arms (26 +/- 2 mmHg x ml(-1) x 100 ml x min) and legs (34 +/- 3 mmHg x ml(-1) x 100 ml x min) but low leg blood flow (1.5 +/- 0.4 ml x 100 ml(-1) x min(-1)). Supine leg Pv (30 +/- 2 vs. 13 +/- 1 mmHg in control) exceeded the threshold for edema (isovolumetric pressure = 19 +/- 3 mmHg). Supine, normal Pv had high blood flow in arms (4.1 +/- 0.2 vs. 3.5 +/- 0.2 ml x 100 ml(-1) x min(-1) in control) and legs (3.8 +/- 0.4 vs. 2.7 +/- 0.3 ml x 100 ml(-1) x min(-1) in control) with low resistance. With tilt, calf blood flow increased steadily in POTS with high Pv and transiently increased in normal Pv. Calf volume increased in all POTS patients. Arm blood flow increased in normal Pv only with forearm maintained at heart level. These data suggest that there are (at least) two subgroups of POTS characterized by high Pv and low flow or normal Pv and high flow. These may correspond to abnormalities in local or baroreceptor-mediated vasoconstriction, respectively.     

Maximal vascular leg conductance in trained and untrained men

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.     

Heterogeneous responses of human limbs to infused adrenergic agonists: a gravitational effect?

Unlike quadrupeds, the legs of humans are regularly exposed to elevated pressures relative to the arms. We hypothesized that this "dependent hypertension" would be associated with altered adrenergic responsiveness. Isoproterenol (0.75-24 ng x 100 ml limb volume-1 x min-1) and phenylephrine (0.025-0.8 microg x 100 ml limb volume-1 x min-1) were infused incrementally in the brachial and femoral arteries of 12 normal volunteers; changes in limb blood flow were quantified by using strain-gauge plethysmography. Compared with the forearm, baseline calf vascular resistance was greater (38.8 +/- 2.5 vs. 26.9 +/- 2.0 mmHg x 100 ml x min x ml-1; P < 0.001) and maximal conductance was lower (46.1 +/- 11.9 vs. 59.4 +/- 13.4 ml x ml-1 x min-1 x mmHg-1; P < 0.03). Vascular conductance did not differ between the two limbs during isoproterenol infusions, whereas decreases in vascular conductance were greater in the calf than the forearm during phenylephrine infusions (P < 0.001). With responses normalized to maximal conductance, the half-maximal response for phenylephrine was significantly less for the calf than the forearm (P < 0.001), whereas the half-maximal response for isoproterenol did not differ between limbs. We conclude that alpha1- but not beta-adrenergic-receptor responsiveness in human limbs is nonuniform. The relatively greater response to alpha1-adrenergic-receptor stimulation in the calf may represent an adaptive mechanism that limits blood pooling and capillary filtration in the legs during standing.     

Sympathetic responses to head-down rotations in humans.

Muscle sympathetic nerve activity (MSNA) increases with head-down neck flexion (HDNF). The present study had three aims: 1) to examine sympathetic and vascular responses to two different magnitudes of HDNF; 2) to examine these same responses during prolonged HDNF; and 3) to determine the influence of nonspecific pressure receptors in the head on MSNA. The first experiment tested responses to two static head positions in the vertical axis [HDNF and intermediate HDNF (I-HDNF; approximately 50% of HDNF)]. MSNA increased above baseline during both I-HDNF and HDNF (from 219 +/- 36 to 301 +/- 47 and from 238 +/- 42 to 356 +/- 59 units/min, respectively; P < 0.01). Calf blood flow (CBF) decreased and calf vascular resistance increased during both I-HDNF and HDNF (P < 0.01). Both the increase in MSNA and the decrease in CBF were linearly related to the magnitude of the downward head rotations (P < 0.01). The second experiment tested responses during prolonged HDNF. MSNA increased (from 223 +/- 63 to 315 +/- 79 units/min; P < 0.01) and CBF decreased (from 3.2 +/- 0.4 to 2.6 +/- 0.04 ml. 100 ml-1. min-1; P < 0.01) at the onset of HDNF. These responses were maintained throughout the 30-min period. Mean arterial blood pressure gradually increased during the 30 min of HDNF (from 94 +/- 4 to 105 +/- 3 mmHg; P < 0.01). In a third experiment, head-down neck extension was performed with subjects in the supine position. Unlike HDNF, head-down neck extension did not affect MSNA. The results from these studies demonstrate that MSNA: 1) increases in magnitude as the degree of HDNF increases; 2) remains elevated above baseline during prolonged HDNF; and 3) responses during HDNF are not associated with nonspecific receptors in the head activated by increases in cerebral pressure.     

Orthostasis fails to produce active limb venoconstriction in adolescents.

Orthostasis is characterized by translocation of blood from the upper body and thorax into dependent venous structures. Although active splanchnic venoconstriction is known to occur, active limb venoconstriction remains controversial. Based on prior work, we initially hypothesized that active venoconstriction does occur in the extremities during orthostasis in response to baroreflex activation. We investigated this hypothesis in the arms and legs of 11 healthy volunteers, aged 13-19 yr, using venous occlusion strain gauge plethysmography to obtain the forearm and calf blood flows and to compute the capacitance vessel volume-pressure compliance relation. Subjects were studied supine and at -10, +20, and +35 degrees to load the baroreflexes. With +20 degrees of tilt, blood flow decreased and limb arterial resistance increased significantly (P < 0.05) compared with supine. With +35 degrees of tilt, blood flow decreased, limb arterial resistance increased, and heart rate increased, indicating parasympathetic withdrawal and sympathetic activation with arterial vasoconstriction. The volume-pressure relation was unchanged by orthostatic maneuvers. The results suggest that active venoconstriction in the limbs is not important to mild orthostatic response.     

Effects of spaceflight on human calf hemodynamics.

Chronic microgravity may modify adaptations of the leg circulation to gravitational pressures. We measured resting calf compliance and blood flow with venous occlusion plethysmography, and arterial blood pressure with sphygmomanometry, in seven subjects before, during, and after spaceflight. Calf vascular resistance equaled mean arterial pressure divided by calf flow. Compliance equaled the slope of the calf volume change and venous occlusion pressure relationship for thigh cuff pressures of 20, 40, 60, and 80 mmHg held for 1, 2, 3, and 4 min, respectively, with 1-min breaks between occlusions. Calf blood flow decreased 41% in microgravity (to 1.15 +/- 0.16 ml x 100 ml(-1) x min(-1)) relative to 1-G supine conditions (1.94 +/- 0.19 ml x 100 ml(-1) x min(-1), P = 0.01), and arterial pressure tended to increase (P = 0.05), such that calf vascular resistance doubled in microgravity (preflight: 43 +/- 4 units; in-flight: 83 +/- 13 units; P < 0.001) yet returned to preflight levels after flight. Calf compliance remained unchanged in microgravity but tended to increase during the first week postflight (P > 0.2). Calf vasoconstriction in microgravity qualitatively agrees with the "upright set-point" hypothesis: the circulation seeks conditions approximating upright posture on Earth. No calf hemodynamic result exhibited obvious mechanistic implications for postflight orthostatic intolerance.     

Persistent splanchnic hyperemia during upright tilt in postural tachycardia syndrome

Previous investigations have allowed for stratification of patients with postural tachycardia syndrome (POTS) on the basis of peripheral blood flow. One such subset, comprising "normal-flow POTS" patients, is characterized by normal peripheral resistance and blood volume in the supine position but thoracic hypovolemia and splanchnic blood pooling in the upright position. We studied 32 consecutive 14- to 22-yr-old POTS patients comprising 13 with low-flow POTS, 14 with normal-flow POTS, and 5 with high-flow POTS and 12 comparably aged healthy volunteers. We measured changes in impedance plethysmographic (IPG) indexes of blood volume and blood flow within thoracic, splanchnic, pelvic (upper leg), and lower leg regional circulations in the supine posture and during incremental tilt to 20 degrees, 35 degrees, and 70 degrees. We validated IPG measures of thoracic and splanchnic blood flow against indocyanine green dye-dilution measurements. We validated IPG leg blood flow against venous occlusion plethysmography. Control subjects developed progressive vasoconstriction with incremental tilt. Splanchnic blood flow was increased in the supine position in normal-flow POTS, despite marked peripheral vasoconstriction, and did not change during incremental tilt, producing progressive splanchnic hypervolemia. Absolute hypovolemia was present in low-flow POTS, all supine flows and volumes were reduced, there was no vasoconstriction with tilt in all segments, and segmental volumes tended to increase uniformly throughout tilt. Lower body (pelvic and leg) flows were increased in high-flow POTS at all angles, with consequent lower body hypervolemia during tilt. Our main finding is selective and maintained orthostatic splanchnic vasodilation in normal-flow POTS, despite marked peripheral vasoconstriction in these same patients. Local splanchnic vasoregulatory factors may counteract vasoconstriction and venoconstriction in these patients. Lower body vasoconstriction in high-flow POTS was abnormal, and vasoconstriction in low-flow POTS was sustained at initially elevated supine levels.     

Reflex constriction of human limb resistance vessels to head-down neck flexion

The effect of head-down neck flexion on forearm and calf blood flow was determined in 10 healthy male subjects. The subject lay prone, with the neck slightly extended and the chin resting on a soft-padded support at the edge of the table. The chin support was then removed, and the subject maximally flexed and lowered the neck. This was followed by return to the initial position. Neck flexion caused a rapid decrease in blood flow in both forearm and calf; at 30 s this averaged 39 and 35%, respectively. The flow in both forearm and calf gradually recovered as the neck flexion was sustained and approached the control values at the end of 10 min. The blood flow at the ankle was unchanged, indicating that the decrease occurred in the skeletal muscles. The arterial blood pressure and heart rate were unchanged; thus the decrease in flow was due to vasoconstriction. The fact that the decrease was evident as soon as the head was lowered indicated that it was nervously mediated. Neither contraction of the flexor muscles of the neck nor venous congestion of the head, in the absence of the head-down position, altered the blood flow. Although the mechanism of the decrease in flow has not been determined, the studies demonstrate that in response to certain stimuli, the resistance vessels in the skeletal muscles of the forearm and calf undergo a similar nervously mediated vasoconstriction.     

Effects of posture on the venodilatory response to nitroglycerin

To determine the effects of posture on the venodilatory response to nitroglycerin (TNG), the change in forearm venous volume after inflation of an upper arm cuff to 30 mmHg above cuff zero (VV[30]) was measured during control conditions and after TNG (0.8 mg spray) in 18 healthy young volunteers in the supine position and the sitting position. VV[30] was 3.24 +/- 0.98 ml/100 ml arm in the supine position and 2.46 +/- 1.32 ml/100 ml arm in the sitting position. TNG increased VV[30] by 0.56 +/- 0.19 ml/100 ml arm in supine subjects, but by only 0.38 +/- 0.17 ml/100 ml arm in sitting subjects (P = 0.013). When limb volume was measured in the forearm and calf without using a cuff to produce venous congestion, the increase in limb volume with TNG was significantly greater in the sitting than in the supine position. Because the fall in both systolic and diastolic pressure and the rise in heart rate were significantly greater after TNG was administered in the sitting position, it is suggested that a greater reflex venoconstriction occurred in this posture, which antagonized the TNG-induced increase in venous distensibility. In the seated position, the effect of gravity more than compensated for the impaired venodilatory response to TNG. These results suggest that TNG causes a greater reduction in venous return to the heart when administered in the sitting position than in the supine position.     

Enhanced maximal metabolic vasodilatation in the dominant forearms of tennis players

In an effort to evaluate potential peripheral adaptations to training, maximal metabolic vasodilation was studied in the dominant and nondominant forearms of six tennis players and six control subjects. Maximal metabolic vasodilation was defined as the peak forearm blood flow measured after release of arterial occlusion, the reactive hyperemic blood flow (RHBF). Two ischemic stimuli were employed in each subject: 5 min of arterial occlusion (RHBF5) and 5 min of arterial occlusion coupled with 1 min of ischemic exercise (RHBF5ex). RHBF and resting forearm blood flows were measured using venous occlusion strain-gauge plethysmography (ml X min-1 X 100 ml-1). Resting forearm blood flows were similar in both arms of both groups. RHBF5ex was similar in both arms of our control group (dominant, 40.8 +/- 1.2 vs. nondominant, 40.9 +/- 2.1). However, RHBF5ex was 42% higher in the dominant than in the nondominant forearms of our tennis player population (dominant, 48.7 +/- 4.0 vs. nondominant, 34.4 +/- 3.4; P less than 0.05). This intraindividual difference in peak forearm blood flows was not secondary to improved systemic conditioning since the maximal O2 consumptions in the two study groups were similar (controls, 45.4 +/- 3.9 vs. tennis players, 46.1 +/- 1.7). These findings suggest a primary peripheral cardiovascular adaptation to exercise training in the dominant forearms of the tennis players resulting in a greater maximal vasodilatation.     

Peripheral vascular resistance increases after termination of obstructive apneas.

The mechanisms by which obstructive apneas produce intermittent surges in arterial pressure remain poorly defined. To determine whether termination of obstructive apneas produce peripheral vasoconstriction, we assessed forearm blood flow during and after obstructive events in sleeping patients experiencing spontaneous upper airway obstructions. In all subjects, heart rate was monitored with an electrocardiogram and blood pressure was monitored continuously with digital plethysmography. In 10 patients (protocol 1), we used forearm plethysmography to assess forearm blood flow, from which we calculated forearm vascular resistance by performing venous occlusions during and after obstructive episodes. In an additional four subjects, we used simultaneous Doppler and B-mode images of the brachial artery to measure blood velocity and arterial diameter, from which we calculated brachial flow continuously during spontaneous apneas (protocol 2). In protocol 1, forearm vascular resistance increased 71% after apnea termination (29.3 +/- 15.4 to 49.8 +/- 26.5 resistance units, P < 0.05) with all patients showing an increase in resistance. In protocol 2, brachial resistance increased at apnea termination in all subjects (219.8 +/- 22.2 to 358.3 +/- 46.1 mmHg x l(-1) x min; P = 0.01). We conclude that termination of obstructive apneas is associated with peripheral vasoconstriction.     

Forearm vascular resistance increases during static exercise in heart transplant recipients.

In heart transplant recipients but not in normal humans, total peripheral vascular resistance increases during static exercise. To determine whether this augmented vasoconstriction limits the vasodilation normally seen in the nonexercising forearm, we measured arterial pressure, heart rate, and forearm blood flow during 30% maximal static handgrip in 9 heart transplant recipients and 10 control subjects. Handgrip evoked comparable increases in mean arterial pressure in the transplant recipients and control subjects (+19 +/- 2 vs. +20 +/- 2 mmHg). Heart rates increased by 14 +/- 3 beats/min in the control subjects but did not change in the transplant recipients. Directionally opposite patterns of forearm vascular resistance were observed in the two groups. In the control subjects, forearm resistance fell during handgrip (-8.8 +/- 1.9 units, P less than 0.05). In contrast, in the transplant recipients, forearm resistance rose during this intervention (+9.0 +/- 2.9 units, P less than 0.05). Thus the vasodilation that normally occurs in the nonexercising forearm during static handgrip is reversed in heart transplant recipients. Vasoconstriction in the forearm contributes to the increase in total peripheral resistance that occurs during static exercise in these individuals.     

Augmentation of the push-pull effect by terminal aortic occlusion during head-down tilt.

Tolerance to positive vertical acceleration (Gz) gravitational stress is reduced when positive Gz stress is preceded by exposure to hypogravity, which is called the "push-pull effect." The purpose of this study was to test the hypothesis that baroreceptor reflexes contribute to the push-pull effect by augmenting the magnitude of simulated hypogravity and thereby augmenting the stimulus to the baroreceptors. We used eye-level blood pressure as a measure of the effectiveness of the blood pressure regulatory systems. The approach was to augment the magnitude of the carotid hypertension (and the hindbody hypotension) when hypogravity was simulated by head-down tilt by mechanically occluding the terminal aorta and the inferior vena cava. Sixteen anesthetized Sprague-Dawley rats were instrumented with a carotid artery catheter and a pneumatic vascular occluder cuff surrounding the terminal aorta and inferior vena cava. Animals were restrained and subjected to a control gravitational (G) profile that consisted of rotation from 0 Gz to 90 degrees head-up tilt (+1 Gz) for 10 s and a push-pull G profile consisting of rotation from 0 Gz to 90 degrees head-down tilt (-1 Gz) for 2 s immediately preceding 10 s of +1 Gz stress. An augmented push-pull G profile consisted of terminal aortic vascular occlusion during 2 s of head-down tilt followed by 10 s of +1 Gz stress. After the onset of head-up tilt, the magnitude of the fall in eye-level blood pressure from baseline was -20 +/- 1.3, -23 +/- 0.7, and -28 +/- 1.6 mmHg for the control, push-pull, and augmented push-pull conditions, respectively, with all three pairwise comparisons achieving statistically significant differences (P < 0.01). Thus augmentation of negative Gz stress with vascular occlusion increased the magnitude of the push-pull effect in anesthetized rats subjected to tilting.     

Dynamic cerebral autoregulation is preserved during acute head-down tilt.

Complete ganglion blockade alters dynamic cerebral autoregulation, suggesting links between systemic autonomic traffic and regulation of cerebral blood flow velocity. We tested the hypothesis that acute head-down tilt, a physiological maneuver that decreases systemic sympathetic activity, would similarly disrupt normal dynamic cerebral autoregulation. We studied 10 healthy young subjects (5 men and 5 women; age 21 +/- 0.88 yr, height 169 +/- 3.1 cm, and weight 76 +/- 6.1 kg). ECG, beat-by-beat arterial pressure, respiratory rate, end-tidal CO2 concentration, and middle cerebral blood flow velocity were recorded continuously while subjects breathed to a metronome. We recorded data during 5-min periods and averaged responses from three Valsalva maneuvers with subjects in both the supine and -10 degrees head-down tilt positions (randomized). Controlled-breathing data were analyzed in the frequency domain with power spectral analysis. The magnitude of input-output relations were determined with cross-spectral techniques. Head-down tilt significantly reduced Valsalva phase IV systolic pressure overshoot from 36 +/- 4.0 (supine position) to 25 +/- 4.0 mmHg (head down) (P = 0.03). Systolic arterial pressure spectral power at the low frequency decreased from 5.7 +/- 1.6 (supine) to 4.4 +/- 1.6 mmHg2 (head down) (P = 0.02), and mean arterial pressure spectral power at the low frequency decreased from 3.3 +/- 0.79 (supine) to 2.0 +/- 0.38 mmHg2 (head down) (P = 0.05). Head-down tilt did not affect cerebral blood flow velocity or the transfer function magnitude and phase angle between arterial pressure and cerebral blood flow velocity. Our results show that in healthy humans, mild physiological manipulation of autonomic activity with acute head-down tilt has no effect on the ability of the cerebral vasculature to regulate flow velocity.     

Effects of forskolin on placental vascular resistance in rabbits

Forskolin is a direct stimulant of adenylate cyclase and increases cAMP production. It also acts as a vasodilator. To study the effect of forskolin infusion on rabbit maternal vascular resistance, we instrumented 11 pregnant rabbits with catheters in the left ventricle, jugular vein, and left and right femoral arteries. After a 2-day recovery period, one of two protocols was performed. In the control period of the first protocol (N = 6), 50% ethanol in saline was infused at 0.103 ml.min-1 for 5-min. Forskolin (10(-3) M) in 50% ethanol was then infused for 5 min at 0.103 ml.min-1. After each infusion period, regional blood flows were measured by microsphere injection. Data are expressed as means +/- SEM. Blood pressure decreased from 81 +/- 3 to 79 +/- 3 mm Hg, (P less than 0.05, N = 10) during forskolin infusion. Total placental resistance fell from 180.3 +/- 10.7 to 133.8 +/- 12.0 mm Hg.min.ml-1 per gram, P less than 0.05. Cerebral, coronary, and renal vascular resistance fell significantly. During the second protocol (N = 5), angiotensin II (0.05 microgram.min-1) was infused for 5 min followed by the addition of forskolin (10(-3) M at 0.103 ml.min-1) to the infusate. Regional blood flows, vascular resistances and blood pressures were determined. Blood pressure fell from 99 +/- 6 to 92 +/- 7 mm Hg (P less than 0.05) when forskolin was added to the infusate. Placental resistance fell from 202.5 +/- 21.6 to 158.0 +/- 29.0 mm Hg.min.ml-1 per gram (P less than 0.05). While cerebral vascular resistance did not change, renal and coronary resistances fell in response to forskolin. This study demonstrates that forskolin is able to dilate rabbit placental vessels alone and in the presence of the vasoconstrictive agent angiotensin II.