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Biomedical subjects

A Ledlow

Publications and source records attributed to A Ledlow.

5 recordsLinked to original sources

Guanylate cyclase inhibitors: effect on tone, relaxation, and cGMP content of lower esophageal sphincter.

Relaxation of the lower esophageal sphincter (LES) results from activation of its intrinsic innervation. This relaxation is associated temporally with an increase in the guanosine 3',5'-cyclic monophosphate (cGMP) content of the muscle. This study tests the hypothesis that variations in the production of cGMP mediate resting LES tone and nerve-induced relaxation. We examined the effects of guanylate cyclase inhibitors, such as cystamine and methylene blue (MB), on the resting tone, resting membrane potential, electrical field stimulation (EFS)-induced relaxation, and cGMP content of circular smooth muscle from the LES of the opossum. Strips of sphincter muscle were placed in a tissue bath and stretched to 125% resting length. Both cystamine and MB increased the resting tone of LES muscle in a concentration-dependent manner (EC50 = 1.1 +/- 0.2, n = 12, and 1.6 +/- 0.4 mM, n = 10, respectively). The increase in tone by cystamine was not blocked by tetrodotoxin, atropine, or propranolol. Cystamine (1 mM) did not alter the resting membrane potential of circular muscle cells of the LES. The removal of extracellular Ca2+ by the addition of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA, 4 mM) and nifedipine (1 microM) shortened the duration but not the amplitude of the response to cystamine. Pretreatment with caffeine (5 mM) in the presence of EGTA and nifedipine to deplete intracellular Ca2+ stores blocked the increase in tone by cystamine. Cystamine (1 mM) failed to inhibit LES relaxation induced by EFS. Carbachol, at a concentration that induced a similar increase in base-line tone, attenuated the nerve-mediated relaxation. Cystamine did not alter basal cGMP levels, but inhibited the rise in cGMP induced by EFS. The data indicate that cystamine increases LES tone but does not inhibit EFS-induced relaxation, even though it inhibits EFS-induced increases in cGMP content. The increase in tone is dependent on the presence of intracellular Ca2+ stores.

Animals

Nitric oxide: mediator of nonadrenergic noncholinergic responses of opossum esophageal muscle.

Nonadrenergic noncholinergic (NANC) nerves of the opossum esophagus mediate relaxation of circular muscle from the lower esophageal sphincter (LES) and the off contraction of circular esophageal muscle. The latencies between the end of the stimulus and the off contraction describe a gradient so that the latency is longest in muscle from the caudad esophagus. NG-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide (NO) synthase, and NO were used to test the hypothesis whether NO is a mediator of these nerve-induced responses. Both electrical field stimulation (EFS) of intrinsic esophageal nerves and exogenous NO relaxed LES muscle. Only EFS-induced relaxation was inhibited by L-NNA [half-maximal response (EC50) = 60.0 +/- 20.0 microM]. L-Arginine, the substrate for NO synthase, reversed the inhibitory effect of L-NNA. Exogenous NO did not contact circular esophageal muscle. Both the amplitude (EC50 = 14.7 +/- 4.0 microM) and the latency of the off contraction (EC50 = 41.1 +/- 5.6 microM) were diminished by L-NNA. L-Arginine prevented the action of L-NNA. NG-nitro-L-arginine also attenuated the gradient in the latency of the off response by shortening latencies in muscle from the caudad esophagus. It had no effect on cholinergic nerve-induced contraction of longitudinal esophageal muscle. These data support the hypothesis that NO or an NO-containing compound may be a mediator of NANC nerve-induced responses of the esophagus and LES.

Animals

Differences in reaction times and average evoked potentials as a function of direct and indirect neural pathways.

Average evoked potentials and manula response latencies were collected during a simple detection task in which brief visual stimuli were presented to the left and right visual fields. Latencies generated by the ipsilateral stimulus-hand combinations were shorter than contralateral combinations only under certain conditions, impugning the hypothesis that the reaction time difference reflects interhemispheric transfer time. Certain evoked potential components recorded contralateral to the stimulus occurred earlier than their ipsilateral counterparts, but whether this difference can be interpreted as representing interhemispheric transfer time is also questioned.

Adult

Reaction times and evoked potentials as indicators of hemispheric differences for laterally presented name and physical matches.

Letter pairs, which could be name matches, physical matches, or mismatches, were presented at fixation or 2.5 degrees left or right of fixation. During different experimental sessions, the locations and the types of matches were fixed (and therefore known in advance by the subject) or were randomized. Right visual field superiority in reaction time occurred for name matches only when location was randomized, and then the extent of the superiority depended on whether the types of match called for were predictable. Evoked potentials to the letter pairs during this task revealed hemispheric and neural pathway differences that were independent of expectancy condition. Right hemisphere responses were larger than left. For some components, amplitudes were smaller and latencies were shorter for direct than for indirect projection of stimuli to each cerebral hemisphere. Indirect-direct differences in P300 amplitude varied for each cerebral hemisphere according to whether a physical or name match occurred. The P130 and N170 components manifested hemispheric differences that depended on whether the two letters of a pair were in the same or different cases.

Adult