Dale E. Claassen

Nonuniform sympathetic nerve responses to intravenous hypertonic saline infusion.

Peripheral hyperosmolality produced by the intravenous infusion of hypertonic saline (HTS) increases mean arterial blood pressure (MAP) in experimental animals. The mechanisms mediating the pressor response have not been fully ascertained, but likely involve vasopressin and/or activation of the sympathetic nervous system. The primary aim of this study was to determine if HTS infusion produces regionally uniform or nonuniform changes in sympathetic nerve discharge (SND). For this purpose we recorded renal, splanchnic and lumbar SND during intravenous HTS infusion (2.5 M NaCl, 10 microliters/100 g BW per min) in chloralose-anesthetized, Sprague-Dawley rats. In rats with intact arterial baroreceptors, HTS infusion significantly increased MAP (17 +/- 2 mmHg) and lumbar SND (29 +/- 13%) but reduced splanchnic (-52 +/- 7%) and renal SND (-33 +/- 8%). After sinoaortic denervation (SAD), HTS infusion significantly increased MAP (28 +/- 6 mmHg) and lumbar SND (27 +/- 9%) and decreased renal SND (-22 +/- 8%). The increase in lumbar SND occurred significantly sooner in SAD compared with baroreceptor-intact rats. In contrast, splanchnic SND remained unchanged from control levels during HTS infusion after SAD. These results demonstrate that HTS infusion produces regionally nonuniform changes in SND, and suggest that the pressor and lumbar sympathoexcitatory responses to HTS infusion are opposed by the arterial baroreceptors.

Impact of altered gravity on aspects of cell biology

Publisher Summary This chapter summarizes the progress that has been made in determining and understanding the effect of gravity on cell function. It describes the results from three general areas of spaceflight research, and within each area, focuses on specific cell systems for which sufficient data have been accumulated. Included are (1) cell physiology, with a focus on immune cell activation; (2) cell development, with a focus on plant cell differentiation; and (3) the physiology of unicellular organisms. In addition, the chapter describes the underlying principles that govern spaceflight research on the cell, and examines experimental approaches used to investigate the effects of altered gravity on cell function. One environmental factor that has remained constant throughout evolution is the force of earths gravitational field. The cardiovascular system counteracts gravity when it pumps blood to the upper body, but also uses the pull of gravity when it distributes fluid to the lower extremities. These well-known adaptations to gravity become clearly evident during manned orbital spaceflight, where the inertial acceleration caused by gravitational force is virtually canceled and the gravity vector is no longer detectable. In this microgravity environment, where mass is nearly weightless, astronauts experience space motion sickness, muscle atrophy and bone demineralization, as well as cardiovascular deconditioning and the redistribution and pooling of body fluids in the upper body.

Regulation of the sympathetic nerve discharge bursting pattern during heat stress

Frequency-domain analyses were used to determine the effect of heat stress on the relationships between the discharge bursts of sympathetic nerve pairs and sympathetic and phrenic nerve pairs in chloralose-anesthetized rats. Sympathetic nerve discharge (SND) was recorded from the renal, splanchnic, splenic, and lumbar nerves during increases in core body temperature (Tc) from 38 to 41.4 ± 0.3°C. The following observations were made: 1) hyperthermia transformed the cardiac-related bursting pattern of SND to a pattern that contained low-frequency, non-cardiac-related bursts, 2) the pattern transformation was uniform in regionally selective sympathetic nerves, 3) hyperthermia enhanced the frequency-domain coupling between SND and phrenic nerve bursts, and 4) low-frequency SND bursts recorded during hyperthermia contained significantly more activity than cardiac-related bursts. We conclude that acute heat stress profoundly affects the organization of neural circuits responsible for the frequency components in sympathetic nerve activity and that SND pattern transformation provides an important strategy for increasing the level of activity in sympathetic nerves during increased Tc.

Altered frequency characteristics of sympathetic nerve activity after sustained elevation in arterial pressure.

We tested the hypothesis that sustained elevation in mean arterial pressure (MAP) alters the frequency-domain characteristics of efferent sympathetic nerve discharge (SND) after the return of MAP to control levels. Renal, lumbar, and splanchnic SND were recorded before, during, and after a 30-min increase in MAP produced by phenylephrine (PE) infusion in α-chloralose-anesthetized, spontaneously hypertensive (SH) rats. The following observations were made. 1) The basic cardiac-locked pattern of renal, lumbar, and splanchnic SND bursts was altered after sustained elevation in MAP, demonstrating prolonged effects on the neural circuits involved in entraining efferent SND to the cardiac cycle. Importantly, discharge bursts in afferent baroreceptor nerve activity remained pulse-synchronous after sustained increases in arterial pressure. 2) The frequency-domain relationships between the activity in sympathetic nerve pairs were altered after sustained elevation in MAP, suggesting a transformation from a system of tightly coupled neural circuits to one of multiple generators exerting selective control over SND. 3) The most prominent reduction in SND power after sustained elevation in MAP occurred in the frequency band containing the cardiac cycle, indicating that the prolonged suppression of SND after sustained increases in arterial pressure is due primarily to the selective inhibition of cardiac-related SND bursts. We conclude that sustained elevation in MAP profoundly affects the neural circuits responsible for the frequency components of basal SND in SH rats.We tested the hypothesis that sustained elevation in mean arterial pressure (MAP) alters the frequency-domain characteristics of efferent sympathetic nerve discharge (SND) after the return of MAP to control levels. Renal, lumbar, and splanchnic SND were recorded before, during, and after a 30-min increase in MAP produced by phenylephrine (PE) infusion in alpha-chloralose-anesthetized, spontaneously hypertensive (SH) rats. The following observations were made. 1) The basic cardiac-locked pattern of renal, lumbar, and splanchnic SND bursts was altered after sustained elevation in MAP, demonstrating prolonged effects on the neural circuits involved in entraining efferent SND to the cardiac cycle. Importantly, discharge bursts in afferent baroreceptor nerve activity remained pulse-synchronous after sustained increases in arterial pressure. 2) The frequency-domain relationships between the activity in sympathetic nerve pairs were altered after sustained elevation in MAP, suggesting a transformation from a system of tightly coupled neural circuits to one of multiple generators exerting selective control over SND. 3) The most prominent reduction in SND power after sustained elevation in MAP occurred in the frequency band containing the cardiac cycle, indicating that the prolonged suppression of SND after sustained increases in arterial pressure is due primarily to the selective inhibition of cardiac-related SND bursts. We conclude that sustained elevation in MAP profoundly affects the neural circuits responsible for the frequency components of basal SND in SH rats.

Effects of microgravity on liposome-reconstituted cardiac gap junction channeling activity.

Effects of microgravity on cardiac gap junction channeling activity were investigated aboard NASA zero-gravity aircraft. Liposome-reconstituted gap junctions were assayed for channel function during free-fall, and the data were compared with channeling at 1 g. Control experiments tested for 0 g effects on the structural stability of liposomes, and on the enzyme-substrate signalling system of the assay. The results demonstrate that short periods of microgravity do not perturb reconstituted cardiac gap junction channeling activity.

Reconstitution of cardiac gap junction channeling activity into liposomes: A functional assay for gap junctions

Cardiac gap junctions were reconstituted into liposomes. To determine if reconstitution resulted in membrane channel formation, we developed an assay for channel function that used a liposome-entrapped peroxidase to detect entry of a substrate into the liposome. The data demonstrate, for the first time, that reconstituted gap junctions from heart are capable of channel-forming activity in artificial membranes.