Biomedical subjects

G A Hand

Publications and source records attributed to G A Hand.

28 records · Page 2Linked to original sources

PubMed1997

Central injection of physostigmine attenuates exercise-induced pressor response in conscious cats.

The effects of intracerebroventricular administration of physostigmine, a cholinesterase inhibitor, on the cardiovascular responses evoked by static voluntary exercise were investigated using conscious cats. Four cats were trained to press a bar (200-650 g) with one forelimb for at least 20 s. The changes in mean arterial pressure (MAP), heart rate (HR), and developed force during the first five trials in 30 min by each individual cat were averaged, and a mean of the four values was then calculated. After the cats exercised for 30 min, either artificial cerebrospinal fluid (CSF) or physostigmine (5 micrograms) was administered intracerebroventricularly. Before physostigmine, exercise trials by the cats increased MAP and HR by 17 +/- 3 mmHg and 42 +/- 4 beats/min, respectively. Administration of physostigmine did not alter the resting MAP and HR but attenuated the MAP and HR responses to exercise (5-30 min postphysostigmine: MAP = 8 +/- 3 mmHg, HR = 25 +/- 7 beats/min; 30-60 min postphysostigmine: MAP = 4 +/- 3 mmHg, HR = 19 +/- 8 beats/min). Intracerebroventricular administration of CSF had no effect on the cardiovascular responses to static exercise. Pretreatment with the muscarinic antagonist, atropine (25 micrograms icv), blocked the attenuating effects of subsequent intracerebroventricular administration of physostigmine. These results demonstrate that stimulation of central muscarinic receptors attenuates the cardiovascular responses to static exercise by conscious cats. In addition, the present study suggests that there is no tonic effect of central muscarinic receptors on the cardiovascular responses to voluntary exercise.

Analysis of Variance↗

PubMed1996

Cardiovascular responses to static exercise in conscious cats: effects of intracerebroventricular injection of clonidine.

1. Static exercise elicits increases in arterial blood pressure and heart rate (HR) in humans and conscious animals. In this study, the effects of intracerebroventricular (I.C.V.) administration of clonidine, an alpha 2-adrenergic agonist, on these cardiovascular responses were investigated using conscious cats. Four cats were operantly trained to extend a forelimb and press a bar (200-650 g) for 15-60 s. A stainless-steel cannula was inserted into the right lateral ventricle for I.C.V. injection of drugs, and a common carotid artery was catheterized to measure mean arterial pressure (MAP) and HR. The number of exercise trials and changes in MAP, HR and force were pooled for 30 min periods. After the cats exercised for 30 min, either artificial cerebrospinal fluid (CSF) or clonidine (2 or 5 micrograms) were administered intracerebroventricularly. 2. Before clonidine injection, fifty-two exercise trials increased MAP and HR by 15 +/- 3 mmHg and 41 +/- 5 beats min-1, respectively. Administration of clonidine (2 micrograms) did not alter the resting MAP and HR, but attenuated the increases in MAP and HR in response to exercise (0-30 min post-clonidine: n = 81; delta MAP, 6 +/- 3 mmHg; delta HR, 20 +/- 6 beats min-1; 30-60 min post-clonidine: n = 71; delta MAP, 4 +/- 4 mmHg; delta HR, 17 +/- 8 beats min-1). Administration of artificial CSF I.C.V. had no effect on the cardiovascular responses to static exercise. 3. An increased dose of clonidine (5 micrograms) decreased resting MAP and HR by 31 +/- 7 mmHg and 37 +/- 7 beats min-1, respectively, and markedly blunted the cardiovascular responses to exercise (pre-clonidine: n = 52; delta MAP, 17 +/- 3 mmHg; delta HR, 38 +/- 5 beats min-1; post-clonidine 0-30 min: n = 66; delta MAP, 4 +/- 2 mmHg; delta HR, 15 +/- 5 beats min-1; post-clonidine 30-60 min: n = 60; delta MAP, 4 +/- 2 mmHg; delta HR, 14 +/- 6 beats min-1). Pretreatment with the alpha 2-adrenergic antagonist, yohimbine (8 micrograms, I.C.V.), blocked the attenuating effects of I.C.V. administration of clonidine (5 micrograms). 4. These results show that stimulation of central alpha 2-adrenoceptors by clonidine attenuates the cardiovascular responses to static exercise in conscious cats. In addition, this study suggests that alpha 2-adrenoceptors blocked by yohimbine injected I.C.V. do not appear to have a tonic influence on HR and blood pressure.

Animals↗

PubMed1996

Microdialysis of a non-NMDA receptor antagonist into the L7 dorsal horn attenuates the pressor response to static muscle contraction but not passive stretch in cats.

Mean arterial pressure (MAP) and heart rate (HR) were measured during static contraction or passive stretch of the triceps surae muscle of chloralose-anaesthetized cats. MAP and HR increased by 46 +/- 5 mmHg and 17 +/- 3 beats min-1, respectively, during a 1 min contraction. Passive stretch of the same muscle for 1 min reflexly increased MAP and HR by 40 +/- 7 mmHg and 14 +/- 3 beats min-1, respectively. Microdialysis of 2 mM 6-cyano-7-nitroquinoxaline-2,3-dione (CNX), a non-NMDA receptor antagonist, into the dorsal horn at the L7 spinal level attenuated the reflex pressor response to static contraction (2 h of dialysis: delta MAP = 23 +/- 5 mmHg, delta HR = 8 +/- 2 beats min-1). By contrast, there was no attenuation of the pressor response to passive stretch at 2 h of CNQX perfusion. However, the simultaneous microdialysis of 2 mM CNQX into the L6 and S1 levels blunted the pressor and tachycardic responses to contraction and stretch. These data show that the reflex pressor response to static muscle contraction is partly mediated by activation of non-NMDA receptors at the level of afferent fibre entry into the dorsal horn and through collateral pathways. Further, it appears that the afferent pathways within the dorsal horn for the signal transduction arising from static muscle contraction and passive stretch of the hindlimb are dissimilar.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1996

Continuous contractile activity induces fiber type specific expression of HSP70 in skeletal muscle.

Continuous contractile activity of skeletal muscle elicits an early and dramatic increase in ribosomal RNA, suggesting that translational efficiency and/or capacity is enhanced during the adaptive response to increased metabolic demand. In view of the important role heat shock or stress proteins (HSPs) play as molecular chaperones during protein synthesis, we examined whether expression of the inducible 70-kDa HSP (HSP70) and/or mitochondrial 60-kDa HSP (HSP60) is altered in rabbit tibialis anterior muscle during continuous low-frequency motor nerve stimulation. Induction of the HSP70 gene was evident within 24 h after the onset of stimulation as reflected by increases in HSP70 transcription (> 20-fold) and mRNA (> 50-fold). HSP70 protein levels were significantly elevated (10- to 12-fold) after 14 and 21 days of stimulation. Mitochondrial HSP60 mRNA and protein also increased during stimulation (> 18- and > 5-fold after 21 days, respectively). In situ hybridization and immunohistochemistry coupled with myosin ATPase staining revealed that expression of HSP70 was restricted to oxidative type I and IIa fibers during the first 3 days of stimulation but shifted to primarily type II fibers after 21 days of stimulation. These findings demonstrate that induction of HSP70 during the adaptive response to chronic motor nerve stimulation proceeds from type I/IIa to type IId(x)/b fibers, suggesting that the expression of HSPs may be required to support the folding and compartmentalization of nascent proteins during the transformation process.

Animals↗

PubMed1996

NMDA receptor blockade in cat dorsal horn blunts reflex pressor response to muscle contraction and stretch.

The role of N-methyl-D-aspartate (NMDA) receptors in the reflex pressor response to static muscle contraction and passive stretch was examined by microdialyzing the NMDA receptor antagonist DL-2-amino-5-phosphonovalerate (AP-5) into the L7 or L6 and S1 levels of the dorsal horn of anesthetized cats. Contraction, elicited by electrical stimulation of the cut L7 and S1 ventral roots, increased mean arterial pressure (MAP) and heart rate (HR). Passive stretch at tensions similar to those generated by contraction also increased these variables. These cardiovascular changes were unaffected by dialyzing AP-5 (10 mM) into the dorsal horn at L7. Increasing the syringe concentration of AP-5 to 100 mM attenuated the pressor and HR responses from 62 +/- 8 to 31 +/- 6 mmHg and 18 +/- 4 to 12 +/- 4 beats/min, respectively. AP-5 blunted the increase in MAP (59 +/- 10 vs. 41 +/- 10 mmHg) evoked by muscle stretch. Simultaneously microdialyzing AP-5 (10 or 100 mM) into the dorsal horn at the L6 and S1 spinal levels also blunted the MAP and HR responses to contraction and stretch. These results suggest that NMDA receptors play a role in mediating the MAP and HR responses to static muscle contraction at the spinal level of the central nervous system. Furthermore, these data demonstrate that collaterals from muscle afferents partially mediate the reflex cardiovascular responses evoked by muscle contraction and stretch.

2-Amino-5-phosphonovalerate↗

PubMed1996

Excitatory amino acid concentrations in the spinal dorsal horn of cats during muscle contraction.

In anesthetized cats, static hindlimb muscle contraction reflexly increases mean arterial pressure (MAP) and heart rate (HR). Pharmacological and immunohistochemical evidence suggests that excitatory amino acids are involved in the spinal transmission of this reflex. Using microdialysis and high-performance liquid chromatography technology, we tested the hypothesis that static contraction of the triceps surae muscle increases the extracellular concentration of glutamate (Glu) and aspartate (Asp) at the L7 level of the dorsal horn of the spinal cord. With the exception of the L7 dorsal root, the L5-S2 dorsal and ventral roots were cut ipsilateral to the contracting muscle. After the insertion of microdialysis probes and a 3-h recovery period, a 2-min static contraction was electrically evoked. MAP and HR increased by 53 +/- 8 mmHg and 20 +/- 4 beats/min. The concentration of Glu increased from 324 +/- 59 to 857 +/- 80 nM, whereas Asp increased from 199 +/- 57 to 499 +/- 113 nM. These results were repeatable, in that Glu and Asp rose by similar amounts in two subsequent contractions. In both of these latter contractions, MAP and HR were also significantly increased. By contrast, in a subset of cats whose L7 dorsal roots were cut after the first contraction, neither MAP, HR, Glu, nor Asp was significantly increased over baseline levels. These data demonstrate that static contraction of the hindlimb increases the extracellular concentration of Glu and Asp in the dorsal horn. In summary, the results from this study are in agreement with previous findings suggesting that excitatory amino acids are involved in the spinal transmission of sensory information from the hindlimb muscle.

Animals↗

PubMed1993

RNA subunit of mitochondrial RNA-processing enzyme is induced by contractile activity in striated muscle.

A small RNA encoded within the nucleus of yeast and mammalian cells is an essential subunit of a mitochondrial RNA-processing endonuclease (RNase MRP) that generates primers for mitochondrial DNA (mtDNA) replication. We examined expression of MRP-RNA in specialized subtypes of mammalian striated muscles that differ markedly in respiratory activity and in muscles subjected to chronic stimulation via the motor nerve, a potent stimulus to mitochondrial biogenesis. MRP-RNA was more abundant in mitochondria-rich cardiac and slow-twitch skeletal muscles than in glycolytic fast-twitch skeletal muscles. Forced contractile activity resulting from nerve stimulation increased expression of MRP-RNA by 3.5-fold within the first day and by 14-fold within 14 days. Changes in abundance of MRP-RNA preceded but otherwise occurred in parallel to changes in specific activity of citrate synthase, a marker of mitochondrial proliferation shown previously to correlate with mtDNA copy number in this model. Another small RNA (U1) also was induced transiently (1-3 days) by nerve stimulation, but such changes were not sustained and were of less magnitude (< 4-fold) than changes in MRP-RNA. These findings are consistent with the hypothesis that MRP-RNA may have a regulatory function with respect to mtDNA replication and mitochondrial biogenesis.

Animals↗

PubMed1992

Sympathoadrenal-circulatory regulation of arterial pressure during orthostatic stress in young and older men.

Our purpose was to test the hypothesis that human aging alters sympathoadrenal-circulatory control of arterial blood pressure during orthostasis. Plasma catecholamine and hemodynamic adjustments to two different forms of orthostatic stress, lower body suction (-10 to -50 mmHg) and standing, were determined in 14 young (26 +/- 1 yr) and 13 older (64 +/- 1) healthy, normally active men. During quiet supine rest, cardiac output tended to be lower and systemic vascular resistance higher in the older men, but no other differences were observed. On average, arterial blood pressure was well maintained during both forms of orthostasis in the two groups; the older men actually demonstrated better maintenance of pressure (P < 0.05) and a lesser incidence of orthostatic hypotension than the young men during lower body suction. Despite a blunted reflex tachycardia during orthostatic stress (P < 0.05), cardiac output tended to decrease less in the older men because of a smaller decline in stroke volume (P < 0.05, suction only), whereas the reflex increases in systemic vascular resistance were not different in the two groups. The whole forearm vasoconstrictor response tended to be attenuated in the older men during lower body suction, but was identical in the two groups with standing. Forearm skin vascular resistance was unaltered during lower body suction in both groups. Orthostasis-evoked increases in antecubital venous plasma norepinephrine concentrations were similar in the young and older men, whereas little or no increases in plasma epinephrine concentrations were observed in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMed1992

Augmented forearm vasoconstriction during dynamic exercise in healthy older men.

BACKGROUND: We tested the hypothesis that the nonactive limb vasoconstriction evoked during large-muscle dynamic exercise becomes augmented with aging in humans. METHODS AND RESULTS: Sixteen young control subjects (age, 26 +/- 1 year) and twelve older (65 +/- 1 year) healthy men with similar chronic physical activity levels were studied during supine leg cycling exercise. Both peak work load (1,100 +/- 60 versus 1,400 +/- 40 kpm/min) and peak O2 uptake (1.85 +/- 0.10 versus 2.38 +/- 0.07 l/min) were lower in the older men (p < 0.05). There were no differences in the two groups under conditions of quiet supine (basal) rest. During cycling for 5 minutes each at mild, moderate, and heavy submaximal intensities (approximately 45%, 65%, and 85% of peak O2 uptake), the increases in arterial blood pressure generally were similar in the young and older subjects; however, heart rate rose less in the older men (p < 0.05). Whole forearm blood flow (venous occlusion plethysmography) was lower and vascular resistance was higher (approximately 55-90%) in the older men at all loads (p < 0.05), but the steady-state forearm skin blood flow responses (laser Doppler velocimetry) were not different in the two groups. The increases in antecubital venous norepinephrine concentrations were greater in the older men at each work load (p < 0.05), although the plasma epinephrine responses were similar in the two groups. In other studies, 1) peak whole forearm reactive hyperemia and vascular conductance after sustained circulatory arrest (ischemia) were slightly (approximately 20%) but not significantly lower in the older men and 2) the forearm vasoconstrictor and plasma norepinephrine responses to a nonexercise sympathoexcitatory stimulus (limb immersion in ice water) tended to be blunted in the older men. CONCLUSIONS: During brief, submaximal, large-muscle dynamic exercise, healthy older men demonstrate augmented forearm vasoconstriction that is probably caused by greater constriction of skeletal muscle resistance vessels; this appears to be mediated, at least in part, by increased sympathetic outflow. These altered sympathetic vasoconstrictor adjustments do not represent a nonspecific hyperresponsiveness to acute stress with human aging. Finally, the regulation of arterial blood pressure appears to be normal in these healthy older men.

Adult↗

PubMed1991

Sympathoadrenal-circulatory regulation during sustained isometric exercise in young and older men.

The aim of this study was to test the hypothesis that the arterial blood pressure, vasoconstrictor, and sympathoadrenal adjustments to sustained submaximal isometric exercise become augmented with advancing age in humans. Fourteen young (26 +/- 1 yr) and 14 older (66 +/- 1 yr) healthy males performed isometric handgrip exercise at 30% of maximal voluntary force until exhaustion (inability to maintain target force). Maximal handgrip force was quite similar in the young and older subjects (402 +/- 20 vs. 392 +/- 20 N, respectively). The two groups did not differ significantly on any variable at rest. During sustained handgrip to exhaustion, peak levels of both perceived exertion and contracting forearm electromyographic activity were similar in the young and older men, suggesting equivalent voluntary efforts. Exercise time was not different in the two groups (315 +/- 27 s in young vs. 339 +/- 17 s in older men). Throughout exercise the increases in arterial blood pressure were very similar in the young and older subjects. Heart rate increased less (P less than 0.05), but stroke volume (impedance cardiography) tended to decrease less (not significant) in the older men; thus the increases in cardiac output were not different in the two groups. During the latter portion of exercise, systemic vascular resistance tended to increase in both the young and older men, with no significant group differences. The blood flow responses in the whole calf (venous occlusion plethysmography) and the calf skin (laser-Doppler velocimetry) were similar in the young and older subjects, as were the corresponding increases in vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗