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R K Goyal

Publications and source records attributed to R K Goyal.

At least 163 records · Page 9Linked to original sources
PubMed1986

Effects of [Na+] and [Ca2+] on the responses to milrinone in rat cardiac preparations.

In the present investigation we have studied the influence of changing the [Ca2+] and [Na+] on the cardiac responses to milrinone in various preparations of rat heart. Milrinone (5 X 10(-5) to 8 X 10(-4) M) produced a dose-dependent positive chronotropic effect on right atrium and a positive inotropic effect on left atrium and papillary muscle of the rat. A decrease in [Ca2+] (from 2.2 to 1.1 mM) or an increase in [Na+] (from 120 to 60 mM) increased the milrinone-induced inotropic effect in left atrium and papillary muscle. However, in right atrium the chronotropic effect of milrinone was significantly decreased under these conditions. Opposite changes to milrinone-induced responses were observed when [Ca2+] was increased (to 3.3 mM) or when the [Na+] was decreased to 60 mM. Nifedipine (3 X 10(-3) M), a selective Ca2+ channel blocker, significantly inhibited the chronotropic response to milrinone in right atrium. However, the inotropic response to milrinone was found to be significantly greater in the presence of nifedipine. A veratridine-induced positive inotropic effect in the left atrium was also significantly increased in the presence of nifedipine. Tetrodotoxin (TTX, 1 X 10(-6) M), a fast sodium channel blocker, significantly reduced the inotropic response to milrinone in left atrium and papillary muscle. A milrinone-induced dose-dependent increase in the baseline tension was observed in the right atrium which was abolished in low [Ca2+] and significantly increased in high [Ca2+]. Our data suggest the possibility that milrinone increases Ca2+ influx in the right atrium to cause the chronotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Structure-activity relationship of subtypes of cholecystokinin receptors in the cat lower esophageal sphincter.

Cholecystokinin (CCK) causes relaxation of the cat lower esophageal sphincter (LES) by stimulating CCK receptors on the noncholinergic, nonadrenergic inhibitory neurons and causes contraction by stimulating CCK receptors on the sphincter muscle. Studies were performed in anesthetized cats to identify differences between the two CCK receptors by investigating the structure-activity relationships of various fragments of CCK or gastrin molecule. Lower esophageal sphincter pressures were monitored continuously, using continuously perfused catheters, and agents were administered intravenously or close intraarterially. Based on their doses and the presence or absence of tetrodotoxin pretreatment, CCK analogues produced either relaxation or contraction of the sphincter. The relative potencies of CCK analogues on the inhibitory (neural) response were CCK-8 greater than G-17-I greater than or equal to dCCK greater than CCK-4(1:1/14,000: 1/15,000: 1/335,000). Sulfated gastrin was nearly as potent as CCK-8. The relative potency of these agents on the contractile (muscle) response was CCK-8 = G-17-I greater than or equal to dCCK-8 greater than CCK-4 (1:1:1/4.5: 1/2000). Deamidated CCK-8 was inactive. Proglumide shifted the dose-response curves of the inhibitory as well as excitatory effects of CCK analogues to the right. These studies show that there are two distinct species of CCK receptors: (a) The CCK alpha receptors, present on the inhibitory neurons, are very discriminative and are critically dependent on SO4; and (b) the CCK beta receptors, present on the sphincter muscle, are not discriminative and are not critically dependent on SO4. Nonsulfated gastrin may share the CCK beta receptors with CCK.

Animals↗
PubMed1986

Role of substance P nerves in longitudinal smooth muscle contractions of the esophagus.

Longitudinal muscle strips from different sites along the opossum esophagus were stimulated transmurally so as to produce neurally mediated contractions. Low-frequency transmural stimulation produced contractions after termination of the stimulus ("off" contractions), whereas high-frequency stimuli produced contractions beginning during the stimulus and extending beyond termination of the stimulus (extended-duration contractions). The intrastimulus portion of the extended-duration contraction was partially antagonized by atropine or substance P desensitization, whereas the poststimulus portion of the contraction was selectively and fully antagonized by desensitization with substance P. A combination of atropine and substance P desensitization abolished the extended-duration contraction. The amplitude of contraction was greater in the proximal than in the distal strips, irrespective of the mode of stimulation. The poststimulus portion of the extended-duration contraction was significantly longer in muscle strips taken from more distal than proximal portions of the esophagus. This gradient in duration of contractions was abolished by substance P desensitization but was not affected by atropine. Exogenously applied substance P (10 microM) produced equally sustained long-duration contractions at all sites along the esophagus. These observations suggest that a) both acetylcholine- and substance P-containing nerves are responsible for the extended-duration contraction of longitudinal muscle, and b) transmural stimulation causes an aborally directed increase in the duration of contractions; this gradient of increasing duration of contraction appears to be due to a more prolonged neural release of substance P at more distal sites.

Animals↗
PubMed1986

Experimental induction of isolated lower esophageal sphincter relaxation in anesthetized opossums.

Isolated lower esophageal sphincter (LES) relaxation, defined as a transient sphincteric relaxation unaccompanied by esophageal peristalsis, has been shown to precede most episodes of gastroesophageal reflux in humans. We studied the genesis of isolated LES relaxation in anesthetized opossums by observing the response of four components of the deglutition reflex (mylohyoid electrical activity, pharyngeal contraction, esophageal peristalsis, and LES relaxation) to pharyngeal tactile stimulation, electrical stimulation of superior laryngeal nerve (SLN) afferents or cervical vagal efferents, and to balloon distention of the esophageal body. A single pharyngeal stroking evoked isolated LES relaxation in 56% of 160 instances. The proportion of isolated relaxations in response to SLN electrical stimulation varied inversely with the stimulus frequency, occurring in 64% of the responses at 5 Hz and 4% of the responses at 30 Hz. A full four-component deglutition sequence was most likely to occur at the higher frequencies of SLN electrical stimulation. Esophageal balloon distention elicited isolated LES relaxations or no response at low distending volumes, whereas at higher volumes LES relaxation and esophageal contraction predominated. Isolated LES relaxation had significantly less magnitude than relaxations accompanied by esophageal contractions. Bilateral cervical vagotomy abolished all LES and esophageal body responses induced by pharyngeal stroking and SLN stimulation, and rendered the esophageal body and LES less responsive to small volumes of distention. Vagal efferent stimulation produced isolated LES relaxation at lower frequency stimulation and LES relaxation with esophageal contractions at higher frequency stimulation. These studies show that isolated LES relaxation represents incomplete expression of either the deglutitive reflex or the peripheral reflex mediating secondary peristalsis.

Anesthesia↗
PubMed1986

A rapid silver-free method for staining the myenteric plexus.

A method is presented for the relatively rapid demonstration of the myenteric plexus. Saturated Sudan black B in 70% ethanol followed by 0.01% aqueous buffered thionein were used on intestinal peels (whole-mounts) to stain myelinated and unmyelinated fibers and neuron cell bodies, respectively. In contrast to accepted silver methods, these two kinds of fibers were distinguished clearly; Schwann cell nuclei and nodes of Ranvier were visible. Preparations had the following attributes: relatively low optical density coupled with high visual contrast, freedom from metallic "mirroring," low background staining of subjacent muscle fibers, and presentation of a polychromatic picture. The entire procedure was under the complete and repeatable control of the operator. Perikaryon and nuclear morphology were clearly demonstrated. The limitations of this method are that it does not provide good visualization of individual unmyelinated neuronal processes and does not permit preparation of permanent slides.

Animals↗
PubMed1986

Effects of hydralazine on streptozotocin-induced diabetic rats: prevention of hyperlipidemia and improvement in cardiac function.

The effects of hydralazine on blood lipids, systolic pressure and cardiac performance were assessed in male Wistar rats, 6 weeks after they were made diabetic with streptozotocin (STZ). STZ-induced diabetes results in a loss of body weight, hyperglycemia and hypoinsulinemia. These effects are not altered after hydralazine treatment. STZ-diabetes also produced a significant bradycardia, elevation of blood pressure, hyperlipidemia and decreases in the levels of triiodothyronine and thyroxine. Hydralazine treatment successfully prevented all these alterations. In addition, cardiac performance was depressed in the untreated diabetic animals, but the cardiac performance of the hydralazine-treated diabetic animals showed a definite improvement. Thus, hydralazine controlled the high serum lipids and blood pressure and improved cardiac performance in STZ diabetic rats.

Animals↗
PubMed1985

Regional gradient of initial inhibition and refractoriness in esophageal smooth muscle.

The influence of two successive vagal stimuli on esophageal contractions was studied by recording intraluminal pressures in the smooth muscle portion of the opossum esophagus. The esophageal contraction in response to the first or second stimulus in a pair of vagal stimuli was inhibited depending on the interstimulus interval, the frequency of the stimulus, and the esophageal site. The esophageal contraction in response to the first vagal stimulus was inhibited by a second vagal stimulus if the latter stimulus was applied before the peak of the first contraction. This phenomenon is termed initial inhibition. Initial inhibition is a graded phenomenon. It was greater at higher frequencies than at lower frequencies (p less than 0.001), and was significantly greater in the distal esophagus than in the proximal esophagus (p less than 0.01). The term "refractoriness" has been used to denote inhibition of the second esophageal contraction by the first. Refractoriness was observed during and beyond the duration of the first esophageal response. Refractoriness was also observed at all esophageal levels; however, the interstimulus intervals that demonstrated refractoriness were significantly greater in the distal than in the proximal esophagus (p less than 0.01). Refractoriness was complete (effective refractory period) during the ascending phase of the first contraction. Refractoriness was incomplete after the peak of the contraction (relative refractory period). These studies show gradients of durations and degrees of initial inhibition and refractoriness along the esophagus. The gradient is responsible for the peristaltic nature of esophageal contraction. The gradients of initial inhibition and refractoriness determine esophageal response to multiple successive swallows.

Animals↗
PubMed1985

Effects of chronic streptozotocin-induced diabetes on the cardiac responses to milrinone.

We have studied the effects of milrinone on various cardiac preparations obtained from 6-week streptozotocin diabetic rats. The basal rate of spontaneously beating right atrium from diabetics was significantly lower as compared with controls. Milrinone (5 X 10(-5) to 8 X 10(-4) M) produced a dose-dependent positive inotropic and positive chronotropic effect in left atrium and right atrium, respectively. The positive chronotropic response to milrinone was slightly increased in right atria from diabetic animals. In papillary muscle neither the maximum response nor the pD2 value of milrinone was altered significantly in diabetic animals. The pD2 values of milrinone in right atrium and left atrium were found to be significantly higher in diabetic preparations compared with controls. The data indicate that the responses to milrinone are either unchanged or enhanced in hearts from diabetic animals.

Animals↗
PubMed1984

Acetylcholinesterase and choline acetyltransferase staining of neurons in the opossum esophagus.

The purpose of the present investigation was to identify and compare cholinergic intramural neurons in the lower esophageal sphincter and esophageal body by histochemical staining for acetylcholinesterase and the enzyme that synthesizes acetylcholine, choline acetyltransferase. Opossums were anesthetized and their abdominal cavity was opened by a midline incision to expose the esophagogastric junction. The lower esophageal sphincter was identified manometerically and localized in situ with markers. Tissues were removed, rapidly frozen in freon cooled with liquid nitrogen and serial cryostat sections were obtained from the lower esophageal sphincter and esophageal body. Sections were stained with one of the above histochemical procedures and adjacent sections were stained with Solachrome cyanin , which differentially stains nerve elements from muscle fibers. The muscle of the lower esophageal sphincter and esophageal body was stained with nonspecific cholinesterase with some selectivity of intensity of reaction in the various smooth muscle layers. All identifiable plexus neurons in the esophagus stained for nonspecific cholinesterase and acetylcholinesterase. Nerve fiber tracts were also stained for acetylcholinesterase within the longitudinal and circular layers of the tunica muscularis. Reaction for choline acetyltransferase showed no staining in the muscle layers or nerve fiber tracts of either part of the esophagus studied; however, selected neurons within the myenteric plexus of both regions (approximately 38%) were reactive. There was no significant difference in the number of positive choline acetyltransferase neurons in the lower esophageal sphincter or esophageal body.

Acetylcholinesterase↗
PubMed1984

Intramural mechanism of esophageal peristalsis: roles of cholinergic and noncholinergic nerves.

We examined the role of peripheral cholinergic and noncholinergic mechanisms in esophageal peristalsis. Intramural nerve elements in rings of circular muscle from six different levels of the opossum esophagus were stimulated transmurally so as to cause neurally mediated muscle contractions. Stimulus frequency was varied from 2 to 40 Hz. An increase in stimulus frequency caused an increase in latencies of contractions in rings from distal esophageal sites and a decrease in latencies in rings from proximal sites. This resulted in a marked slowing of the calculated peristaltic speed. Increasing stimulus frequency also caused an increase in duration and amplitude of contractions. These effects were reversed by atropine (0.1 microM), suggesting that higher stimulus frequencies recruited more cholinergic nerves. In the presence of atropine, increasing the stimulus frequency caused an increase in latencies of contraction at all sites, suggesting that increasing stimulation frequency applied to noncholinergic nerves causes an increase in latencies of contraction at all sites. The results of this study indicate that both noncholinergic and cholinergic nerves play a role in the peripheral mechanism of esophageal peristalsis. Cholinergic nerve stimulation reduces the latency and enhances the amplitude and duration of contractions seen with noncholinergic nerve stimulation alone. The influence of cholinergic innervation is most prominent proximally and decreases distally along the smooth muscle portion of the esophagus. This peripherally located gradient of cholinergic innervation plays an important role in determining the speed and amplitude of esophageal peristalsis.

Animals↗
PubMed1984

Characteristics of "on" and "off" contractions in esophageal circular muscle in vitro.

The prevalence, amplitude, and latency periods of "on," "off," and "intermediate" contractions in response to transmural stimulation were recorded in transverse rings of circular muscle from different levels of the opossum esophagus. Ten-second train stimuli consistently produced off contractions. On contractions were not seen at lower stimulus frequencies (2 and 5 Hz); however, their incidence approached 90% at higher frequencies (40 Hz). Intermediate contractions occurred only at stimulus frequencies of 10 Hz or greater and were less frequent than on contractions. In general, the on and intermediate contractions had significantly lower amplitudes than the off contraction. The on contraction occurred with a latency period from initiation of the stimulus. This latency was greater in the more distal sites and decreased with increasing stimulus frequency. The off contractions occurred with a latency period from termination of the stimulus. This latency was not dependent on either stimulus frequency or site along the esophagus. Atropine antagonized the on and intermediate contractions but had no such effect on the off contraction. Tetrodotoxin abolished the on, off, and intermediate contractions. This study suggests that an intramural mechanism exists that upon stimulation produces atropine-sensitive on contractions. These contractions may play a role in esophageal peristalsis.

Animals↗
PubMed1984

Mechanical and electrical activity of esophageal smooth muscle during peristalsis.

Mechanical events and membrane potential changes in response to evoked swallows and cervical vagal stimulation (10 and 40 Hz) were recorded in anesthetized opossums. Miniature strain-gauge transducers monitored the mechanical activity of the two layers. A suction electrode recorded from the intact esophagus, from a proximally based pedicle flap of longitudinal muscle (LM), and from circular muscle (CM). The onset of swallowing was marked by the onset of mylohyoid activity. During swallows LM contraction preceded CM contraction and was of longer duration. The latencies of LM and CM contraction were 1,980 +/- 38 and 2,250 +/- 101 ms, respectively. The durations of contraction of LM and CM were 5,590 +/- 260 and 3,330 +/- 67 ms, respectively. LM showed no hyperpolarization but showed depolarization and spike burst. The CM showed prompt hyperpolarization followed by depolarization and spike burst. Responses to vagal stimulation were qualitatively similar to swallows. The different components of the responses were quantitatively modified by changes in stimulus frequency. These studies show that, during peristalsis in response to swallows and vagal stimulation, 1) LM contraction occurs before CM and is of longer duration, and 2) unlike CM, LM does not hyperpolarize prior to depolarization.

Animals↗
PubMed1984

Swallowing induces sequential activation of esophageal longitudinal smooth muscle.

We examined the mechanical activity of the longitudinal and circular muscles of the esophagus at three different levels (9, 5, and 1 cm above the lower esophageal sphincter) during peristalsis induced by swallows or vagal stimulation in anesthetized opossums with miniature strain gauges applied in the axis of muscle fibers. The onset of longitudinal muscle contraction occurred in an aboral sequence with swallows but simultaneously with vagal stimulation. The speed of longitudinal muscle activation with swallows was 7.6 +/- 1.7 cm/s. Circular muscle contraction occurred in an aboral sequence with vagal stimulation and swallowing with speeds of 4.1 +/- 0.8 and 2.3 +/- 0.1 cm/s, respectively. Longitudinal muscle contracted before the circular muscle at all sites. The duration of longitudinal muscle contraction increased aborally (P less than 0.05) with swallowing or vagal stimulation. These studies show that 1) during swallowing, esophageal longitudinal and circular smooth muscle contract in a sequential fashion, 2) the longitudinal muscle sequential contraction is due to central mechanisms, whereas circular muscle sequential contraction may be due to both central and peripheral mechanisms, and 3) peripheral neuromuscular mechanisms produce regional differences in the duration of longitudinal muscle contraction.

Animals↗
PubMed1984

Swallow-evoked action potentials in vagal preganglionic efferents.

Swallow-evoked potentials in the preganglionic vagal fibers were studied using the single-fiber recording technique in anesthetized opossums. Swallows were evoked by tactile pharyngeal stimulation or electrical stimulation of the cut central end of the superior laryngeal nerve (SLN). Swallowing activity was recorded by the mylohyoid electromyogram and esophageal motility. Sixty-six fibers were studied in which swallowing evoked action potentials. The latencies (from the onset of mylohyoid activity) of evoked responses in different fibers varied from 100 ms to 5 s. The discharge rate of the evoked response was 3-8 action potentials per burst. Each burst lasted 1.1 +/- 0.02 (SE)s. The latencies of evoked spike bursts showed a bimodal distribution. In 34 fibers the latencies were less than 1 s, and in 32 fibers the latencies ranged between 1 and 5 s; these are the short- and long-latency fibers, respectively. Short-latency fibers could easily be distinguished from long-latency fibers based on the influence of SLN-stimulus frequency. Short-latency discharges had low thresholds of activation and were sensitive to changes in the frequency of SLN stimulation, since their latencies decreased and their discharge rate increased with increasing SLN-stimulus frequency. On the other hand, the latencies and discharge rates of long-latency discharges were not modified with changing SLN stimulus frequencies. The conduction velocities of 6 short- and 9 long-latency fibers were 5.64 +/- 0.12 and 5.78 +/- 0.12 (SE) m/s, respectively (P greater than 0.05). The relationship between the latencies of swallow-evoked discharges in the short- and long-latency fibers and the esophageal smooth muscle responses suggested that the short-latency discharges may correlate with the latency of initial inhibition, and the long-latency fibers may correlate with latencies of peristaltic contractions. Based on these temporal relationships, we speculate that vagal efferent fibers showing swallow-evoked, short-latency discharges make contact with intramural inhibitory neurons. They may mediate deglutitive inhibition in the body of the esophagus, relaxation of the lower esophageal sphincter, and receptive relaxation of the fundus of the stomach. The fibers showing late discharges make contact with intramural excitatory neurons and participate in their sequential activation. This dual pathway of activation may be responsible for physiological esophageal peristalsis.

Animals↗