Cardiovascular responses to orthostatic and other stressors in men and women are independent of sex.

1. Cardiovascular responses to the stress of orthostasis, forearm (FA) ischaemia (reactive hyperaemia) and FA exercise (postexercise hyperaemia) are well described. Although sex differences in responses to orthostatic stress have been reported, few studies have examined the impact of sex on reactive hyperaemia and none has commented with regard to postexercise hyperaemia. 2. We investigated 11 men (mean (+/-SEM) age 18.5 +/- 0.3 years) and 10 women (18.8 +/- 0.8 years), all of whom were sedentary, with women being studied in the mid-follicular phase of their menstrual cycle. We measured blood pressure (BP), heart rate (HR) and forearm blood flow (FBF) in response to a fixed sequence of orthostatic, ischaemic and exercise stressors. 3. Orthostatic stress (10 min at -50 mmHg lower body negative pressure; LBNP) induced presyncopal signs in one man and three women. In all other subjects, BP was well maintained, with FBF decreasing and HR increasing similarly in both sexes. The tachycardia was earlier in onset in men and reached significantly higher absolute levels in women during the final 5 min of LBNP, but the percentage changes and integrated responses of both HR and FBF were not different between sexes. 4. The increases in FBF following either 10 min FA ischaemia or 10 min FA exercise were similar in men and women in terms of peak blood flow, percentage change, rate of recovery and total blood flow response. 5. In conclusion, although women were less tolerant of orthostatic stress than men, the cardiovascular responses to this and the other stressors appeared essentially independent of sex.

Body position affects performance in untrained cyclists.

OBJECTIVE: To compare cardiovascular and ventilatory variables in upright versus aero cycle ergometry at submaximal and maximal exercise intensities in untrained cyclists. METHOD: Ten physically active men (mean (SD) age 19.1 (1.10) years) who were unfamiliar with aerobars underwent maximal exercise testing and steady state cycling at 50, 100, and 150 W. RESULTS: Participants had significantly greater maxima for oxygen uptake (VO2), ventilation, heart rate, and workload maximum in the upright position. During steady state cycling at the three workloads, VO2 (ml/kg/min) and gross mechanical efficiency were significantly greater in the upright position. CONCLUSIONS: In untrained subjects performing with maximal effort, the upright position permits greater VO2, ventilation, heart rate, and workload maxima. Further, in the steady state, exercise cycling may be less costly in the upright position. For this reason, untrained cyclists need to weigh body position effects against the well known aerodynamic advantages of the aero position.

No difference in net uptake or disposal of lactate by trained and untrained forearms during incremental sodium lactate infusion.

A number of training adaptations in skeletal muscle might be expected to enhance lactate extraction during hyperlactataemia. The aim of the present study was to determine whether resting endurance-trained forearms exhibit an increased net lactate removal during hyperlactataemia. Six racquet-sport players attended the laboratory for two experiments, separated by 2 weeks. In the first experiment incremental handgrip exercise to fatigue was performed to identify trained (TRFA, n = 6) and untrained (UTFA, n = 5) forearms. In the second experiment net forearm lactate exchange was compared between TRFA and UTFA during an incremental infusion of sodium lactate. TRFA performed more work than UTFA during handgrip exercise [mean (SE) TRFA, 66.1 (9.5) J.100 ml(-1); UTFA, 35.1 (2.3) J.100 ml(-1); P = 0.02] and UTFA exhibited a greater increase in net lactate output relative to work load (P = 0.003). During lactate infusion net lactate uptake across the resting forearms increased linearly with the arterial lactate concentration in both groups (TRFA, r = -0.95 (0.03); UTFA, r= -0.92 (0.04); P < 0.02], with no difference in the regression slopes [TRFA, -1.06 (0.13); UTFA, -1.07 (0.27); P = 0.97] or y-intercepts [TRFA, 0.67 (0.20); UTFA, 1.36 (0.67); P = 0.37] between groups. Almost all of the lactate taken up was disposed of by both groups of forearms [TRFA, 99.6 (0.2)%; UTFA, 98.5 (1.0)%; P = 0.37]. It was concluded that the net uptake and removal of lactate by resting skeletal muscle is a function of the concentration of lactate in the blood perfusing the muscle rather than the muscle training status.

Arterial hypoxaemia in endurance athletes is greater during running than cycling.

The effect of both training discipline and exercise modality on exercise-induced hypoxaemia (EIH) was examined in seven runners and six cyclists during 5 min high intensity treadmill and cycle exercise. There were no significant interactions between training discipline, exercise modality and arterial P(O(2)) (Pa(O(2))) when subject groups were considered separately but when pooled there were significant differences between exercise modalities. After min 2 of exercise arterial hydrogen ion concentration, minute ventilation, alveolar P(O(2)) (PA(O(2))) and Pa(O(2)) were all lower with treadmill running with the largest differential for the latter occurring at min 5 (treadmill, 80.8+/-1.8; cycle, 90.2+/-2.5, mmHg, N=13, P< or = 0.05). At every min of exercise, the differences in Pa(O(2)) between the ergometers were strongly associated with similar differences in PA(O(2)) and alveolar to arterial P(O(2)) (PA(O(2))-Pa(O(2))). It is concluded that the greater EIH with treadmill running is a consequence of the combined effect of a reduced lactic acidosis-induced hyperventilation and greater ventilation-perfusion inequality with this exercise mode.

Pulmonary gas exchange during exercise in highly trained cyclists with arterial hypoxemia.

The causes of exercise-induced hypoxemia (EIH) remain unclear. We studied the mechanisms of EIH in highly trained cyclists. Five subjects had no significant change from resting arterial PO(2) (Pa(O(2)); 92.1 +/- 2.6 Torr) during maximal exercise (C), and seven subjects (E) had a >10-Torr reduction in Pa(O(2)) (81.7 +/- 4.5 Torr). Later, they were studied at rest and during various exercise intensities by using the multiple inert gas elimination technique in normoxia and hypoxia (13.2% O(2)). During normoxia at 90% peak O(2) consumption, Pa(O(2)) was lower in E compared with C (87 +/- 4 vs. 97 +/- 6 Torr, P < 0.001) and alveolar-to-arterial O(2) tension difference (A-aDO(2)) was greater (33 +/- 4 vs. 23 +/- 1 Torr, P < 0. 001). Diffusion limitation accounted for 23 (E) and 13 Torr (C) of the A-aDO(2) (P < 0.01). There were no significant differences between groups in arterial PCO(2) (Pa(CO(2))) or ventilation-perfusion (VA/Q) inequality as measured by the log SD of the perfusion distribution (logSD(Q)). Stepwise multiple linear regression revealed that lung O(2) diffusing capacity (DL(O(2))), logSD(Q), and Pa(CO(2)) each accounted for approximately 30% of the variance in Pa(O(2)) (r = 0.95, P < 0.001). These data suggest that EIH has a multifactorial etiology related to DL(O(2)), VA/Q inequality, and ventilation.

Exercise-induced hypoxaemia in highly trained cyclists at 40% peak oxygen uptake.

A group of 15 competitive male cyclists [mean peak oxygen uptake, VO2peak 68.5 (SEM 1.5 ml x kg(-1) x min(-1))] exercised on a cycle ergometer in a protocol which began at an intensity of 150 W and was increased by 25 W every 2 min until the subject was exhausted. Blood samples were taken from the radial artery at the end of each exercise intensity to determine the partial pressures of blood gases and oxyhaemoglobin saturation (SaO2), with all values corrected for rectal temperature. The SaO2 was also monitored continuously by ear oximetry. A significant decrease in the partial pressure of oxygen in arterial blood (PaO2) was seen at the first exercise intensity (150 W, about 40% VO2peak). A further significant decrease in PaO2 occurred at 200 W, whereafter it remained stable but still significantly below the values at rest, with the lowest value being measured at 350 W [87.0 (SEM 1.9) mmHg]. The partial pressure of carbon dioxide in arterial blood (PaCO2) was unchanged up to an exercise intensity of 250 W whereafter it exhibited a significant downward trend to reach its lowest value at an exercise intensity of 375 W [34.5 (SEM 0.5) mmHg]. During both the first (150 W) and final exercise intensities (VO2peak) PaO2 was correlated significantly with both partial pressure of oxygen in alveolar gas (P(A)O2, r = 0.81 and r = 0.70, respectively) and alveolar-arterial difference in oxygen partial pressure (P(A-a)O2, r = 0.63 and r = 0.86, respectively) but not with PaCO2. At VO2peak PaO2 was significantly correlated with the ventilatory equivalents for both oxygen uptake and carbon dioxide output (r = 0.58 and r = 0.53, respectively). When both P(A)O2 and P(A-a)O2 were combined in a multiple linear regression model, at least 95% of the variance in PaO2 could be explained at both 150 W and VO2peak. A significant downward trend in SaO2 was seen with increasing exercise intensity with the lowest value at 375 W [94.6 (SEM 0.3)%]. Oximetry estimates of SaO2 were significantly higher than blood measurements at all times throughout exercise and no significant decrease from rest was seen until 350 W. The significant correlations between PaO2 and P(A)O2 with the first exercise intensity and at VO2peak led to the conclusion that inadequate hyperventilation is a major contributor to exercise-induced hypoxaemia.

Accuracy of two pulse oximeters during maximal cycling exercise.

This study compared the measurement of oxygen saturation of haemoglobin (SaO2) by two pulse oximeters (Ohmeda Biox 3700e and Criticare 504 USP) with the measurement of SaO2 in arterial blood samples by CO-oximetry. Unlike many previous validation studies, arterial blood was sampled in ground glass rather than plastic syringes. Twenty men, 11 well-trained cyclists (mean +/- SE, age = 23.3 +/- 1.5 years, mass = 71.4 +/- 1.1 kg VO2max = 77 +/- 1 ml.kg1.min-1) and 9 relatively untrained subjects (age = 27.1 +/- 2.8 years, mass = 78.1 +/- 2.2 kg VO2max = 51 +/- 3 ml.kg 1.min-1) performed two maximal cycle ergometer tests each in an hypobaric chamber. The tests were at 745 mm Hg or 695 mm Hg with simultaneous measurement of SaO2 by the pulse oximeters and the CO-oximeter at rest, minute 7 of exercise and at VO2max. The best correlations, to the Co-oximeter measurement (SCO-OXO2) were found when all data from rest and exercise were combined (Criticare: r = 0.94; Ohmeda: r = 0.91). The bias measurements showed the Ohmeda underestimated SCO-OXO2 at all levels (mean = -2.5 +/- 1.9%) and the Criticare overestimated SCO-OXO2 at all levels, although to a lesser degree (mean = 0.9 +/- 1.5%). In conclusion, these results highlight the need for validation of individual pulse oximeters and that the effect of dyshaemoglobins must also be considered.

Training-induced increases in sea level VO2max and endurance are not enhanced by acute hypobaric exposure.

The present study used untrained subjects to examine the effect of acute hypobaric exposure during endurance training on subsequent exercise performance at sea level. Two groups, each of nine subjects, completed 5 weeks of endurance training [cycle ergometer exercise for 45 min, three times per week at a heart rate corresponding to 70% of that achieved at the maximal O2 consumption (VO2max) either at sea level or at high altitude] in a hypobaric chamber, under either normobaric [sea level, SL; 750 mmHg (100 kPa) approximately 90 m] or hypobaric [altitude, ALT; 554 mmHg (73.4 kPa) approximately 2500 m] conditions and the changes in SL VO2max, SL endurance time and peak blood lactate during the endurance test compared. While each group showed increases in both SL VO2max (approximately 12%) and SL endurance time (approximately 71%), there were no significant differences between the groups [SL VO2max, mean (SE)-SL group: pre-training = 42.4 (3.5), post-training = 46.1 (3.5) ml.kg-1.min-1, P < 0.005; ALT group: pre-training = 40.8 (2.6), post-training = 47.2 (3.4) ml.kg-1.min-1, P < 0.01; SL endurance time-SL group: pre-training 7.1 (1.5), post-training 11.8 (2.9) min, P < 0.01; ALT group: pre-training = 7.5 (0.6), post-training = 13.3 (1.4) min, P < 0.001]. Peak blood lactate during the endurance test was not altered by either training regimen. It is concluded that acute exposure of untrained subjects to hypobaric hypoxia during endurance training has no synergistic effect on the degree of improvement in either SL VO2max or endurance time.

Reduced performance of male and female athletes at 580 m altitude.

This study examined the effect of mild hypobaria (MH) on the peak oxygen consumption (VO2peak) and performance of ten trained male athletes [x (SEM); VO2peak = 72.4 (2.2) ml x kg(-1) x min(-1)] and ten trained female athletes [VO2peak = 60.8 (2.1) ml x kg(-1) x min(-1)]. Subjects performed 5-min maximal work tests on a cycle ergometer within a hypobaric chamber at both normobaria (N, 99.33 kPa) and at MH (92.66 kPa), using a counter-balanced design. MH was equivalent to 580 m altitude. VO2peak at MH decreased significantly compared with N in both men [-5.9 (0.9)%] and women [-3.7 (1.0)%]. Performance (total kJ) at MH was also reduced significantly in men [-3.6 (0.8)%] and women [-3.8 (1.2)%]. Arterial oxyhaemoglobin saturation (SaO2) at VO2peak was significantly lower at MH compared with N in both men [90.1 (0.6)% versus 92.0 (0.6)%] and women [89.7 (3.1)% versus 92.1 (3.0)%]. While SaO2 at VO2peak was not different between men and women, it was concluded that relative, rather than absolute. VO2peak may be a more appropriate predictor of exercise-induced hypoxaemia. For men and women, it was calculated that 67-76% of the decrease in VO2peak could be accounted for by a decrease in O2 delivery, which indicates that reduced O2 tension at mild altitude (580 m) leads to impairment of exercise performance in a maximal work bout lasting approximately 5 min.

Effect of muscle glycogen availability on maximal exercise performance.

This investigation determined the influence of pre-exercise muscle glycogen availability on performance during high intensity exercise. Nine trained male cyclists were studied during 75 s of all-out exercise on an air-braked cycle ergometer following muscle glycogen-lowering exercise and consumption of diets (energy content approximately 14 MJ) that were either high (HCHO(80% CHO) or low (LCHO-25% CHO) in carbohydrate content. The exercise-diet regimen was successful in producing differences in pre-exercise muscle glycogen contents [HCHO: 578(SEM 55) mmol x kg(-1) dry mass; LCHO: 364 (SEM 58) P < 0.05 mmol x kg(-1) dry mass]. Despite this difference in muscle glycogen availability, there were no between trial differences for peak power [HCHO 1185 (SEM 50)W, LCHO 1179 (SEM 48)W], mean power [HCHO 547 (SEM 5)W, LCHO 554 (SEM 8)W] and maximal accumulated oxygen deficit [HCHO 54.4 (SEM 2.3) ml x kg(-1), LCHO 54.6 (SEM 2.0) ml x kg(-1)]. Postexercise muscle lactate contents (HCHO 95.9 (SEM 4.6) mmol x kg(-1) dry mass, LCHO 82.7 (SEM 12.3) mmol x kg(-1) dry mass, n = 8] were no different between the two trials, nor were venous blood lactate concentrations immediately after and during recovery from exercise. These results would indicate that increased muscle glycogen availability has no direct effect on performance during all-out high intensity exercise.

Increased arterial desaturation in trained cyclists during maximal exercise at 580 m altitude.

This study utilized a hypobaric chamber to compare the effects of mild hypobaria (MH; 50 mmHg, approximately 580 m altitude) on blood O2 status and maximal O2 consumption (VO2max) in 9 untrained and 11 trained (T) cyclists with VO2max values of 51 +/- 3 and 77 +/- 1 ml.kg-1.min-1, respectively. In both groups, arterial O2 saturation (SaO2) decreased significantly during maximal exercise, and this effect was enhanced with MH. Both these responses were significantly greater in the T cyclists in whom the final SaO2 during MH was 86.5 +/- 0.9%. When the group data were combined, approximately 65% of the variance in SaO2 could be attributed to a widened alveolar-arterial Po2 difference. The arterial PO2 during maximal exercise at sea level in the T group was on the steeper portion of the hemoglobin-O2-loading curve (T, 68.3 +/- 1.3 Torr; untrained, 89.0 +/- 2.9 Torr) such that a similar decrease in arterial PO2 in the two groups in response to MH resulted in a significantly greater fall in both SaO2 and calculated O2 content in the T group. As a consequence, the VO2max fell significantly only in the T group (mean change, -6.8 +/- 1.5%; range, + 1.2 to - 12.3%), with approximately 70% of this decrease being due to a fall in O2 content. This is the lowest altitude reported to decrease VO2max, suggesting that T athletes are more susceptible to a fall in inspired PO2.

Lactate kinetics in resting and exercising forearms during moderate-intensity supine leg exercise.

Arterial blood lactate was elevated by supine leg exercise (20 min at approximately 65% maximal oxygen uptake) in five untrained male subjects, and the contribution to blood lactate removal from passive uptake vs. metabolic disposal was compared in resting and lightly exercising (15% maximal voluntary contraction static handgrip) forearm skeletal muscle. An integrated form of the Fick equation was used to predict venous lactate levels resulting solely from passive equilibration of lactate between incoming arterial blood and the forearm muscles. In the resting forearm, predicted and measured venous lactate levels were closely correlated during the exercise period (r = 0.995, P < 0.001), indicating that lactate removal could be accounted for in terms of passive uptake alone. In the lightly exercising forearm, measured venous lactate levels were higher than both the arterial and predicted venous levels, indicating net lactate production. It was concluded that most of the blood lactate generated by moderate-intensity supine leg exercise is taken up passively and not metabolized by resting skeletal muscle and that the rate of lactate disposal is unlikely to be enhanced in lightly exercising muscle.

Lactate disposal in resting trained and untrained forearm skeletal muscle during high intensity leg exercise.

At a given oxygen uptake (VO2) and exercise intensity blood lactate concentrations are lower following endurance training. While decreased production of lactate by trained skeletal muscle is the commonly accepted cause, the contribution from increased lactate removal, comprising both uptake and metabolic disposal, has been less frequently examined. In the present study the role of resting skeletal muscle in the removal of an arterial lactate load (approximately 11 mmol.l-1) generated during high intensity supine leg exercise (20 min at approximately 83% maximal oxygen uptake) was compared in the untrained (UT) and trained (T) forearms of five male squash players. Forearm blood flow and the venoarterial lactate concentration gradient were measured and a modified form of the Fick equation used to determine the relative contributions to lactate removal of passive uptake and metabolic disposal. Significant lactate uptake and disposal were observed in both forearms without any change in forearm VO2. Neither the quantity of lactate taken up [UT, 344.2 (SEM 118.8) mumol.100 ml-1; T, 330.3 (SEM 85.3) mumol.100 ml-1] nor the quantity disposed of [UT, 284.0 (SEM 123.3) mumol.100 ml-1, approximately 83% of lactate uptake; T, 300.8 (SEM 77.7) mumol.100 ml-1, approximately 91% of lactate uptake] differed between the two forearms. It is concluded that while significant lactate disposal occurs in resting skeletal muscle during high intensity exercise the lower blood lactate concentrations following endurance training are unlikely to result from an increase in lactate removal by resting trained skeletal muscle.

Carbohydrate metabolism during exercise in hot and thermoneutral environments.

This study compared the effects of moderately intense exercise in hot and thermoneutral environments on muscle glycogen and carbohydrate utilization. Well-trained, heat acclimatized cyclists (n = 7) rode at 73.6 +/- 1.1% maximal oxygen consumption for 60 min in a thermoneutral room (23.5 +/- 0.6 degrees C, 52.7 +/- 2.9 relative humidity) or an environmental chamber (33.7 +/- 0.1 degrees C, 49.1 +/- 1.8% relative humidity). During each exercise bout, the subjects received 125 ml of water every 15 min. Muscle biopsies from the vastus lateralis were obtained prior to and following each exercise bout. Exercise in the heat significantly elevated rectal temperature and heart rate above and reduced body weight and plasma volume below that produced by exercise in a thermoneutral environment. Plasma glucose and blood lactate concentrations were similar between treatments prior to exercise, but increased to a greater concentration (p < 0.05) when exercise was performed in the heat. No differences between treatments were found for blood glycerol or free fatty acid concentrations, carbohydrate oxidation or muscle glycogen utilization. These results suggest that moderately intense exercise in the heat, as opposed to a thermoneutral environment, does not increase the rate of muscle glycogenolysis or carbohydrate oxidation in well conditioned, heat acclimatized subjects.

Renin-angiotensin and autonomic mechanisms in cardiovascular homeostasis during haemorrhage in fetal and neonatal sheep.

The present study examined the roles of the renin-angiotensin and autonomic nervous systems in cardiovascular homeostasis during slow progressive haemorrhage (20% of measured blood volume over 1h) in fetal (128-132 and 143-148 days gestation) and neonatal (5-9 and 12-20 days post-natal) sheep. Basal plasma renin activity (PRA) was not significantly different in the 4 sheep groups and increased to a similar degree (approximately 2 to 3-fold) during haemorrhage. Mean arterial pressure (MAP) exhibited modest falls in response to haemorrhage in all sheep groups and while heart rate (HR) was well maintained in the fetal groups there was a tendency to bradycardia in neonates. None of these responses was significantly different in age-matched fetal sheep subjected to bilateral vago-sympathectomy, cervical cord transection or bilateral nephrectomy, with the exception of PRA in the latter group which was close to zero throughout. Treatment with the angiotensin II (AII) antagonist, (Sar1-Ala8) AII (Saralasin), significantly increased basal PRA in both fetal and neonatal sheep (approximately 5 to 7-fold). The PRA response to haemorrhage was absent in neonatal sheep treated with Saralasin but significantly increased in fetal sheep. Saralasin significantly reduced resting MAP in both sheep groups and increased the hypotensive and bradycardic effects of haemorrhage in neonatal (approximately 3 to 5-fold) but not fetal sheep. It is concluded that in the perinatal period studied, fetal and neonatal sheep are equally well able to maintain cardiovascular homeostasis in response to moderate haemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma volume, osmolarity, total protein and electrolytes during treadmill running and cycle ergometer exercise.

While haemoconcentration due to loss of plasma volume is well established during cycling, the existence of similar changes during running remains contentious. This study compared the changes in plasma volume and associated blood indices during 60 min of running and cycling at the same relative intensity (approximately 65% VO2max), with all changes referenced to blood indices obtained after 30 min seated at rest on a cycle ergometer. Plasma osmolarity increased similarly with both forms of exercise but was less than predicted for water loss alone, such that there was a net loss of sodium during exercise and of potassium postexercise, with essentially no loss of protein. Plasma volume decreased similarly (approximately 6.5%) in both exercise trials, but while that with cycling was initiated by exercise itself and was essentially maximal within 5 min, the reduction in plasma volume in the running trial was induced by adopting the upright posture and was complete before exercise began. These data would indicate that different mechanisms are responsible for the changes in plasma volume induced by running and cycling, while the similarity of change would suggest that there is a lower limit to any reduction in plasma volume, regardless of mechanism. Furthermore, the observation that the changes in plasma volume were complete before or early in exercise, would imply that oral water ingestion during prolonged exercise, which is essential for thermoregulation, may be more concerned with homeostasis of extravascular water rather than plasma volume.

Hormonal factors in the control of heart rate in normoxaemic and hypoxaemic fetal, neonatal and adult sheep.

The relationship of plasma levels of adrenaline, noradrenaline, arginine vasopressin (AVP) and plasma renin activity (PRA) to heart rate were studied in normoxaemic and hypoxaemic fetal, neonatal and adult sheep. The mean heart rate response of fetuses at the end of a 30 minute period of 10% oxygen delivery to the maternal ewe was tachycardia. However bradycardia, usually of a transient nature, was observed in 9 of the 12 fetuses (P less than 0.05). Multiple regression analysis was used to determine the contribution of blood gas, blood pressure and plasma hormone levels to the variance in heart rate in the perinatal sheep. 22% of the variance in fetal heart rate was provided by PRA and age from conception (P less than 0.001). Tachycardia was the invariable heart rate response of the neonates and adults to hypoxaemia. 61% of the variance in neonatal heart rate was contributed by PaO2, PaCO2, AVP, PRA and systolic blood pressure (SBP, P less than 0.001). PaO2 and plasma levels of adrenaline were significantly related to adult heart rate (P less than 0.001). Those fetuses which developed bradycardia had lower PaO2 but higher AVP and PRA during hypoxaemia than those which did not develop bradycardia. The major determinant of the area of the fetal bradycardia response was found, by multiple regression analysis, to be plasma adrenaline concentration (P less than 0.05). Thus different hormonal factors may play a role in the regulation of heart rate in normoxaemic and hypoxaemic fetal, neonatal and adult sheep.

Age dependent heart rate responses to prostacyclin (PGI2) in unanaesthetized fetal and neonatal sheep.

Intravenous injections of PGI2 (1.5-12 X 10(-5) nmol/ml blood volume) caused hypotensive responses which increased with dose in both fetal and neonatal sheep. In the fetus, as gestation advanced and basal heart rate declined, the predominant heart rate response to PGI2 changed progressively from bradycardia to tachycardia. In the neonate, PGI2 always induced tachycardia and the effect was unrelated to postnatal age. The bradycardia induced by PGI2 in young fetal sheep (123-132 days) was converted to tachycardia following either bilateral vagotomy or cervical cord transection. Heart rate was unchanged by PGI2 in fetal sheep subjected to both procedures. The depressor response to PGI2 was enhanced by cervical cord transection but was essentially unchanged in fetal sheep subjected to either bilateral vagotomy alone or combined vagotomy and cord section. Despite increased plasma renin activity following PGI2, the cardiovascular response was not modified by bilateral nephrectomy. It is concluded that while intravenous PGI2 has a similar depressor effect in both fetal and neonatal sheep the heart rate response is age-dependent. Bradycardia is the principal response in young fetal sheep and is mediated by vagal pathways while tachycardia, which is the more usual response in older sheep, is probably sympathetic in nature.

Vagal involvement in the pressor responses to cranial artery infusions of bradykinin in anaesthetised greyhounds.

In anaesthetised greyhounds, vertebral and carotid artery infusions of bradykinin increased blood pressure whereas intravenous infusions caused a decrease. With each route of administration, heart rate and cardiac output increased while total peripheral resistance fell. With cranial artery infusions, the consecutive pretreatments of propranolol, phentolamine and vagal cooling resulted in a progressive reduction in the heart rate responses and conversion of the pressor to depressor responses. The responses to intravenous infusions of bradykinin were little changed. In contrast, when the initial pretreatment was interruption of vagal transmission, cranial artery infusions of bradykinin were at once depressor and the depressor response to intravenous infusions immediately enhanced. Subsequent propranolol and phentolamine were without further effect on the blood pressure responses although propranolol did reduce the tachycardia responses. It is concluded that while the tachycardia induced by cranial artery infusions of bradykinin has both cardiac sympathetic and vagal withdrawal components, the hypertensive action is mediated by an increase in cardiac output due largely to withdrawal of cardiac vagal tone.

Angiotensin I and II in the assessment of baroreceptor function in fetal and neonatal sheep.

In fetal and neonatal sheep intravenous injections of angiotensin I, angiotensin II and noradrenaline each increased mean blood pressure and decreased heart rate in a dose-dependent manner. Blood pressure responses to given doses of angiotensin I and II were larger in neonatal than fetal animals while the reverse was true for noradrenaline. In both sheep groups angiotensin II was more pressor than angiotensin I. Baroreceptor function was assessed by correlating blood pressure response to angiotensin II with corresponding changes in either heart rate or heart period. A more sensitive baroreceptor reflex was found in the fetal group in that a given blood pressure response resulted in a significantly larger bradycardia and the calculated gain of the reflex was higher. In those fetuses subjected to either bilateral vagotomy or cervical cord transection pressor responses to both angiotensin II and noradrenaline were enhanced but a significant change was only seen in the cervical cord transection fetuses. Heart rate responses to these drugs were essentially unchanged in the cervical cord transected fetuses while in vagotomized fetuses the bradycardia with each drug was replaced by a tachycardia. It is concluded that the baroreflex is more active in the fetus than the neonate and is mediated by autonomic effector mechanisms similar to those found in the adult.