Janeen M. Hill

Discharge of group IV phrenic afferent fibers increases during diaphragmatic fatigue.

The discharge of single unit group III (n=7) and group IV (n=8) phrenic afferent fibers was recorded during rhythmic diaphragmatic contractions before and after the onset of fatigue. Compared to pre-fatigue impulse activity, group IV, but not group III, phrenic afferent fibers discharged more (p<0.05) during rhythmic diaphragmatic contractions when the diaphragm was fatigued. This increase in group IV fiber discharge during diaphragmatic fatigue provides electrophysiological evidence consistent with the notion that group IV phrenic afferent fibers comprise the afferent arm of a fatigue-induced inhibitory reflex originating in the diaphragm.

Increase in the discharge of muscle spindles during diaphragm fatigue.

The discharge of 18 single unit spindles located in the right crural diaphragm was recorded during rhythmic diaphragmatic contractions before the onset of and during fatigue. Spindle discharge was significantly greater (P<0.05) during rhythmic exercise when the diaphragm was fatigued than spindle discharge during rhythmic exercise when the diaphragm was not fatigued. The increase in spindle discharge during diaphragmatic fatigue is inconsistent with the notion that spindles comprise the afferent arm of a fatigue-induced inhibitory reflex originating in the diaphragm.

Central command, but not muscle reflex, stimulates cutaneous sympathetic efferents of cats

We determined the effects of stimulation of the mesencephalic locomotor region (MLR) and the muscle reflex, each evoked separately, on the discharge of cutaneous sympathetic fibers innervating the hairy skin of decerebrate cats. Electrical stimulation of the MLR was performed while the cats were paralyzed with vecuronium bromide. The muscle reflex was evoked while the cats were not paralyzed by electrical stimulation of the tibial nerve at current intensities that did not activate directly group III and IV muscle afferents. MLR stimulation increased, on average, the discharge of the 23 cutaneous sympathetic fibers tested (P < 0.05). The muscle reflex, in contrast, had no overall effect on the discharge of 21 sympathetic fibers tested (P > 0.05). Both maneuvers markedly increased mean arterial pressure and heart rate (P < 0.05). Prevention of the baroreceptor reflex with the alpha-adrenergic blocking agent phentolamine did not reveal a stimulatory effect of the muscle reflex on cutaneous sympathetic discharge. We conclude that the MLR is a more important mechanism than is the muscle reflex in controlling sympathetic discharge to hairy skin during dynamic exercise.We determined the effects of stimulation of the mesencephalic locomotor region (MLR) and the muscle reflex, each evoked separately, on the discharge of cutaneous sympathetic fibers innervating the hairy skin of decerebrate cats. Electrical stimulation of the MLR was performed while the cats were paralyzed with vecuronium bromide. The muscle reflex was evoked while the cats were not paralyzed by electrical stimulation of the tibial nerve at current intensities that did not activate directly group III and IV muscle afferents. MLR stimulation increased, on average, the discharge of the 23 cutaneous sympathetic fibers tested ( P < 0.05). The muscle reflex, in contrast, had no overall effect on the discharge of 21 sympathetic fibers tested ( P > 0.05). Both maneuvers markedly increased mean arterial pressure and heart rate ( P < 0.05). Prevention of the baroreceptor reflex with the α-adrenergic blocking agent phentolamine did not reveal a stimulatory effect of the muscle reflex on cutaneous sympathetic discharge. We conclude that the MLR is a more important mechanism than is the muscle reflex in controlling sympathetic discharge to hairy skin during dynamic exercise.

Sex Differences in Hepatic Gluconeogenic Capacity After Chronic Alcohol Consumption

Alcohol-induced hypoglycemia has traditionally been attributed to the amount of ethanol consumed rather than any inherent decline in glucose output capacity by the gluconeogenic organs and/or an increase in skeletal muscle glucose uptake. Further, while the potential for sex differences that might impact glucose homeostasis following chronic alcohol consumption has been recognized, direct evidence has been noticeably absent. This paper will provide a brief review of past and present reports of the potential for sex differences in glucose homeostasis following chronic ethanol consumption. This paper will also provide direct evidence from our laboratory demonstrating sex differences from chronic alcohol consumption resulting in a decrement in glucose appearance and more importantly, a specific decline in hepatic gluconeogenic (HGN) capacity in the absence and presence of ethanol. All our studies involved 8 weeks of chronic alcohol consumption in male and female Wistar rats, as well as a 24 to 48 hour fast to deplete hepatic glycogen stores. Under the conditions of chronic alcohol consumption and an acute dose of ethanol, we provide in vivo evidence of an early decline in whole body glucose appearance in females fed an ethanol diet compared to controls. While the decline was also observed in males fed the alcohol diet, it occurred much later compared to ethanol fed females. The site for the decline in whole body glucose production (i.e., either the kidneys or the liver) was beyond the scope of our prior in vivo study. In a follow-up study using the in situ perfused liver preparation, we provide additional evidence for a specific reduction in HGN capacity from lactate in ethanol fed females compared to ethanol fed males in the absence of alcohol in the perfusion medium. Finally, employing the isolated hepatocyte technique, we report decrements in HGN from lactate in ethanol fed females compared to ethanol fed males in the presence of ethanol in the incubation medium. The mechanism for the specific decline in HGN within the liver of ethanol fed females remains to be determined. To the extent that our observations in animals can be extrapolated to humans, we conclude that alcoholic women are more susceptible to ethanol-induced hypoglycemia compared to alcoholic men.

Intrathecal serotonin attenuates the pressor response to static contraction

We tested the hypothesis that intrathecal injection of serotonin onto the lumbosacral spinal cord of chloralose-anesthetized cats attenuates the pressor response to static contraction of the triceps surae muscles. Serotonin (10 micrograms) significantly attenuated the contraction-induced reflex increases in mean arterial pressure but not in ventilation. This attenuation of the reflex pressor response to static contraction by serotonin was prevented by prior intrathecal injection of mianserin hydrochloride, a serotonergic receptor antagonist. In addition, the reflex pressor response to contraction was significantly attenuated by intrathecal injection of carboxamidotryptamine maleate, a 5-HT1 agonist but not by DOI-hydrochloride, a 5-HT2 agonist. We conclude that stimulation of 5-HT1 receptors in the lumbosacral spinal cord attenuates the reflex pressor response to static muscular contraction.

Pressor responses to stimulation of non-NMDA receptors in the superficial laminae of the cat spinal cord

Microinjection of L-glutamate (109 mM; 12-18 nl) or AMPA (150-300 microM; 12 nl) into the superficial laminae of the L7 dorsal horn of decerebrate or chloralose anesthetized cats significantly increased mean arterial pressure. In contrast, microinjection of NMDA (300 microM; 12 nl) had no effect on mean arterial pressure. The pressor response to L-glutamate microinjection was blocked by prior microinjection of CNQX, an antagonist to non-NMDA receptors, but not by AP-5, an antagonist to NMDA receptors. We conclude that stimulation of non-NMDA receptors in the superficial laminae of the lumbar dorsal horn increases arterial blood pressure.

Cardiovascular and respiratory response to static exercise in the newborn kitten

ABSTRACT: Muscle contraction produces a reflex increase in blood pressure, heart rate, and minute ventilation in adults. To evaluate the role of this reflex in newborns, we compared the blood pressure, heart rate, and ventilatory responses to static contraction of the hindlimb muscles in sedated newborn and adult felines. The reflex response to muscle contraction was compared with the baroreflex, the chemoreceptor reflex, and the response to maximal stimulation of sciatic nerve afferents. With muscle contraction, newborn systolic blood pressure increased by 8.5 ± 2.6%, which was significantly less than the adult response of 15.9 ± 1.8% (p < 0.025). Heart rate response to muscle contraction was less in newborns compared with adults, increasing by 1.4 ± 0.5 and 8.3 ± 1.3%, respectively (p < 0.025). In contrast to heart-rate and blood-pressure responses, ventilatory responses to muscle contraction were similar in both age groups, increasing by 34 ± 20 and 34 ± 10% in newborns and adults, respectively. With stimulation of sciatic nerve afferents and with hypoxemia, blood pressure and heart rate increased similarly in both newborns and adults. When the baroreflex was elicited, heart rate decreased similarly in both age groups. We conclude that newborn cats have a reduced heart rate and blood pressure response to muscle contraction compared with the adult. We speculate that the postnatal development of this reflex is due to maturation of integrative and modulatory mechanisms in the CNS.

Substance P analogues potentiate the pressor response to microinjection of L-glutamate into laminas I and II of the cat dorsal horn.

Microinjection of a substance P analogue (1 mM; 7 or 10 nl) into laminae I and II of the L7 dorsal horn of decerebrate cats significantly potentiated (P < 0.05) the increase in arterial pressure evoked by microinjection of L-glutamate (109 mM; 7 or 10 nl) into these spinal sites. Microinjection of the substance P analogues (i.e., GR73638 and [Sar9,Met(O2)11]-substance P) which were selective NK-1 receptor agonists, had no impact on the cardioacceleration evoked by microinjection of L-glutamate (P > 0.05). In addition, microinjection of these analogues had no effect on the modest and non-significant increase in phrenic nerve discharge evoked by L-glutamate. We conclude that stimulation of NK-1 receptors in the superficial laminae of the dorsal horn potentiates the pressor responses to microinjection of L-glutamate.