Much more potent baroreflex sympathetic control of vascular resistance in the resting human limb than previously believed

The concept that, in man, the sympathetic control of the resting limb vascular resistance is truly limited and thus strikingly different from animal species, was challenged in the present study. Analyses were performed in healthy male volunteers of reflex forearm vascular resistance changes evoked by lower body negative pressure (LBNP) ranging from low (15 mmHg) to high and barely tolerated (85 mmHg) levels. Graded LBNP was associated with graded increases in resistance. At high 85 mmHg LBNP the responses were pronounced with a rise in forearm resistance to no less than 120 mmHg ml^-1 min 100+ ml soft tissue, on average, corresponding to a 377% increase above control. This drastic response seemed entirely neurogenic in origin and calculations, based on the likely assumption that a similar response occurred in all skeletal muscle and skin/(subcutaneous fat), showed that it permitted a marked increment in total systemic vascular resistance because of the fact that these tissues constitute so large a proportion of the body mass. The conclusion was reached that the studied tissues may serve as main targets for powerful homeostatic reflexes. It is also suggested, in contrast to current views, that the high-pressure arterial rather than the low-pressure cardio-pulmonary baroreceptors may be the main mediators of haemodynamically important vasoconstrictor responses.     

Sympathetic baroreflex control of vascular resistance in comfortably warm man. Analyses of neurogenic constrictor responses in the resting forearm and in its separate skeletal muscle and skin tissue compartments

Resting forearm vascular resistance changes elicited in male volunteers by graded reflex sympathetic activation evoked by graded lower body negative pressure (LBNP) were studied at room temperatures of 24–25 and 2C–21 7deg;C. The latter condition caused strong suppression of skin flow and permitted preferential analysis of muscle responses and, by comparison with responses at 24–25 7deg;C, secondary estimation of circulatory reactions in the skin. Short-lasting LBNP-bouts (1.5 min) allowed analyses of reflex vascular reactions to high and barely tolerated LBNP (85 mmHg) and thereby to high levels of circulatory stress and sympathetic nerve discharge, yet without risks for the subjects under study. Both muscle and skin reacted intensely and in a graded manner to graded sympathetic activation with very pronounced resistance change (74–77% flow decline; 350–400% resistance rise above control level) at high LBNP. Therefore, the sympathetic vasomotor fibres can exert a very potent control of vascular resistance both in skeletal muscle and in skin under thermoneutral conditions, and both tissues apparently can serve as major targets for powerful sympathetic homeostatic baroreflexes. Evidence indicated that this control is exerted from both low-pressure cardiopulmonary and high-pressure arterial baroreceptor areas. These conclusions deviate from previous literature, in which baroreflex sympathetic vasoconstriction in the human limb has been proposed to be more or less selectively mediated from cardiopulmonary receptors and, further, muscle to respond fully already at mild circulatory stress without further constriction if the stimulus is increased.     

Skeletal muscle and skin as targets for powerful homeostatic vasomotor baroreflexes in humans during prolonged circulatory stress: a study on the innervated and nerve blocked forearm

Flow (vascular resistance) was followed in the innervated and axillary nerve blocked arm during prolonged low to high and barely tolerated circulatory stress [15–85 mmHg LBNP (lower body negative pressure) for 10min; room temperature 24.8–25.7 ^oC]. With intact innervation LBNP caused initial graded and potent forearm vasoconstriction. At low LBNP, however, there was soon significant and maintained partial (50%) abolition of the early response. At high LBNP, the initial striking vasoconstriction remained constant throughout 10 min of pronounced circulatory stress [marked tachycardia; fall in systolic pressure but mean arterial pressure (MAP) normal]. Flow decreased in steady state by 15 + 4, 38 + 5, 63 + 2 and by pronounced 78 + 3 % at 15, 40, 70, and 85 mmHg LBNP (resistance raised 27±7, 78+16, 192+18, and 387±55% above control), alterations ascribed to constriction in both muscle and skin. Comparison of LBNP responses with intact and blocked innervation revealed that the vasoconstriction was neurogenic with little or no humoral contribution. The overall observations show that under normal comfortable (thermoneutral) conditions the resistance vessels in muscle and skin, with haemodynamically important large tissue mass and great tolerance to even drastic and prolonged ischaemia, indeed are important targets in the homeostatic sympathetic control, especially when cardiovascular homeostasis is challenged by marked stress with urgent need for strong, maintained compensatory vasoconstriction. The study also demonstrated > three-fold (4.1 +0.5 to 13.1 + 1.9 ml min^-1 100 ml^-1) forearm flow increases upon blockade of resting nervous vasoconstrictor tone. It thus appears that the sympathetic nerves not only can elicit prominent and maintained baroreflex limb vasoconstriction but also that, in humans, reflex inhibition of resting tone might allow surprisingly large resistance decline.     

Decreased capacitance response with age in lower limbs of humans – a potential error in the study of cardiovascular reflexes in ageing

The cardiovascular regulation in humans depends to a major extent on sympathetic reflexes originating from volume receptors in the arterial as well as the cardiopulmonary region. With experimental approaches, such as lower body negative pressure (LBNP) and tilting, signs of reduced efficiency with ageing have been shown. However, a confounding factor may be an age-related decline in venous capacitance response of the lower limbs, reducing the decrease in central blood volume and thus the deactivation of baro/cardiopulmonary receptors. This potential error was addressed in the present study. Central hypovolaemic stress was produced by LBNP 60 cmH₂O in 10 young (mean age 23, range 20–25 years) and 10 old males (mean age 65, range 61–70 years). Changes in tissue volume of the calf were studied by strain gauge volumetric technique. Transmission of negative pressure to the calf muscle was studied in two young and two old volunteers. The haemodynamic response to hypovolaemic circulatory stress was attenuated in the old as compared with the young subjects, with a less marked increase in heart rate and peripheral resistance. Further, in the old subjects, the decrease in systolic blood pressure, pulse pressure and forearm blood flow was attenuated. Transmission of negative pressure to the calf was equal in both groups. The capacitance response was reduced with age from 2.27 ± 0.14 to 1.64 ± 0.13 mL 100 mL^?1 (P < 0.005). However, the net capillary fluid filtration was unchanged. The reduced capacitance function might partly explain the declining reflex responses with age in humans, and thus seems to be of considerable importance when studying cardiovascular sympathetic reflex responses in ageing.