Peripheral chemoreceptor afferent information is sent to the nucleus tractus solitarii (nTS), integrated, and relayed to other brain regions to alter cardiorespiratory function. The nTS projects to the hypothalamic paraventricular nucleus (PVN), but activation and phenotype of these projections during chemoreflex stimulation is unknown. We hypothesized that activation of PVN-projecting nTS neurons occurs primarily at high intensities of hypoxia. We assessed ventilation and cardiovascular parameters in response to increasing severities of hypoxia. Retrograde tracers were used to label nTS PVN-projecting neurons and, in some rats, rostral ventrolateral medulla (RVLM)-projecting neurons. Immunohistochemistry was performed to identify nTS cells that were activated (Fos-immunoreactive, Fos-IR), catecholaminergic, and GABAergic following hypoxia. Conscious rats underwent 3 h normoxia ( n = 4, 21% O2) or acute hypoxia (12, 10, or 8% O2; n = 5 each). Hypoxia increased ventilation and the number of Fos-IR nTS cells (21%, 13 ± 2; 12%, 58 ± 4; 10%, 166 ± 22; 8%, 186 ± 6). Fos expression after 10% O2was similar whether arterial pressure was allowed to decrease (−13 ± 1 mmHg) or was held constant. The percentage of PVN-projecting cells activated was intensity dependent, but contrary to our hypothesis, PVN-projecting nTS cells exhibiting Fos-IR were found at all hypoxic intensities. Notably, at all intensities of hypoxia, ∼75% of the activated PVN-projecting nTS neurons were catecholaminergic. Compared with RVLM-projecting cells, a greater percentage of PVN-projecting nTS cells was activated by 10% O2. Data suggest that increasing hypoxic intensity activates nTS PVN-projecting cells, especially catecholaminergic, PVN-projecting neurons. The nTS to PVN catecholaminergic pathway may be critical even at lower levels of chemoreflex activation and more important to cardiorespiratory responses than previously considered.

The effect of cardiovascular deconditioning on baroreflex control of the sympathetic nervous system was evaluated after 14 days of hindlimb unloading (HU) or the control condition. Rats were chronically instrumented with catheters and sympathetic nerve recording electrodes for measurement of mean arterial pressure (MAP) and heart rate (HR) and recording of lumbar (LSNA) or renal (RSNA) sympathetic nerve activity. Experiments were conducted 24 h after surgery, with the animals in a normal posture. Baroreflex function was assessed using a logistic function that related HR and LSNA or RSNA to MAP during infusion of phenylephrine and nitroprusside. Baroreflex influence on HR was not affected by HU. Maximum baroreflex-elicited LSNA was significantly reduced in HU rats (204 ± 11.9 vs. 342 ± 30.6% baseline LSNA), as was maximum reflex gain (−4.0 ± 0.6 vs. −7.8 ± 1.3 %LSNA/mmHg). Maximum baroreflex-elicited RSNA (259 ± 10.8 vs. 453 ± 28.0% baseline RSNA), minimum baroreflex-elicited RSNA (−2 ± 2.8 vs. 13 ± 4.5% baseline RSNA), and maximum gain (−5.8 ± 0.5 vs. −13.6 ± 3.1 %RSNA/mmHg) were significantly decreased in HU rats. Results demonstrate that baroreflex modulation of sympathetic nervous system activity is attenuated after cardiovascular deconditioning in rodents. Data suggest that alterations in the arterial baroreflex may contribute to orthostatic intolerance after a period of bedrest or spaceflight in humans.

Prolonged bed rest and exposure to weightlessness in humans result in cardiovascular alterations that are characterized by orthostatic intolerance and decreased exercise capacity. Modifications of cardiovascular function have been suggested to be causally related to changes in peripheral vascular reactivity. Rat hindlimb unweighting (HU) was used as an animal model to determine whether prolonged decreases in weight-bearing activity induce changes in vasoreactivity of peripheral arterial vessels. Responses to vasoactive compounds were examined in vitro using isolated abdominal and thoracic aortic rings. Maximal isometric contractile tension evoked by the vasoconstrictors KCl (10-100 mM), norepinephrine (NE; 10(-9)-10(-4) M), phenylephrine (10(-9)-10(-4) M), arginine vasopressin (10(-13)-3 x 10(-5) M), and CaCl2 (10(-6)-10(-2) M) was lower in abdominal aortic rings from HU rats. Sensitivity [agonist concentration that produced 50% of maximal vasoconstrictor response (EC50)] to KCl was enhanced in segments from HU animals but was not different for the other constrictors. Maximal contractile responses of thoracic aortic rings to KCl (10-100 mM) and NE (10(-9)-10(-4) M) were also attenuated by HU. In abdominal aortic rings preconstricted with 10(-4) M NE, maximal vasodilatory responses induced by sodium nitroprusside (10(-10)-10(-4) M) and 8-bromoguanosine 3',5'-cyclic monophosphate (10(-6)-10(-2) M) were greater in vessel rings from HU rats. However, with 10(-7) M NE preconstriction, maximal dilatory responses induced by sodium nitroprusside (10(-10)-10(-4) M) and acetylcholine (10(-9)-10(-4) M) were not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Age-related changes in skeletal muscle mass, fiber area, and contractile function were examined in pathogen-free rats at 6, 12, 28 and 36 mos of age. The intent of this study was to clarify age-related decline, particularly in contractile force, and to determine if the decline in contractile tension with age is due to alterations at the neuromuscular junction. A variable amount of age-associated reduction in muscle mass was noted for the soleus (18%), extensor digitorum longus (EDL-16%), plantaris (37%), and gastrocnemius (38%) muscles. The decline in fiber area for these four muscles was between 5 and 16% greater than the loss in muscle wet weight. A variable amount of change in peak contractile force between 6 and 36 mos was observed for the soleus (62%), EDL (48%), and plantaris (34%). For soleus and EDL, the decline in peak tetanic tension exceeded the decline in muscle mass and fiber area. Most of the declines for the animals used in this study did not become significant until after the age of 28 mo. The marked reduction in peak tetanic tension, fiber area, and muscle mass between 28 and 36 mos indicates an accelerated age-related decline in this time period. The reduced peak twitch and peak tetanic tension in the oldest animals was not due to likely age-related changes at the neuromuscular junction. Peak values for tetanic tension were similar, whether tension was elicited via direct muscle stimulation or through stimulation of the nerve. Results underscore the complexity of age-related change and suggest that multiple mechanisms contribute to the decline of skeletal muscle.