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Biomedical subjects

R K Goyal

Publications and source records attributed to R K Goyal.

At least 109 records · Page 6Linked to original sources
PubMed1995

Muscarinic suppression of ATP-sensitive K+ channel in rabbit esophageal smooth muscle.

Smooth muscle cells from the rabbit esophageal muscularis mucosae were studied for the presence of ATP-sensitive K+ channel (KATP) and its inhibition by carbachol. Lemakalim (10 microM), a synthetic K+ channel opener, increased whole cell currents by -174 +/- 15 pA with 0.1 mM intracellular ATP concentration ([ATP]i) and -70 +/- 11 pA with 5 mM [ATP]i. Glibenclamide (10 microM) completely abolished the lemakalim-induced currents. These currents were therefore denoted as KATP. Carbachol (10 microM) suppressed KATP by 74 +/- 4% with 10 mM intracellular ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) concentration and 100% when EGTA was omitted from the pipette solution. Carbachol suppression was attenuated to 23 +/- 16% by the M3 receptor antagonist, p-flurohexahydrosiladifenidol (0.1 microM). KATP was also suppressed by phorbol 12-myristate 13-acetate (PMA; 100 nM) by 63 +/- 9%. The effects of both PMA and carbachol were significantly reduced by inhibitors of protein kinase C and tyrosine kinase. These results suggest that carbachol suppression of KATP is via M3 receptor subtype and the signaling pathway involves Ca2+, protein kinase C, and tyrosine kinase.

Adenosine Triphosphate↗
PubMed1995

Transient outward current in opossum esophageal circular muscle.

The whole cell patch-clamp technique was used to record a transient outward K+ current (ITO) from single smooth muscle cells isolated from opossum esophageal circular muscle. The threshold for its activation was -50 mV from holding potentials negative to -70 mV. The current peaked within 10 ms and decayed completely in 200 ms between test depolarization of -40 and -10 mV. ITO was recorded at room temperature in the presence of 5 mM internal ethylene glycol-bis(beta-amino-ethyl ether)-N,N,N',N'-tetraacetic acid. Both activation and inactivation kinetics of ITO were markedly changed when recordings were made at higher temperatures (32 degrees C). 4-Amino-pyridine (4-AP, 3 mM) abolished the fast component of the outward current. Tetraethylammonium ion (TEA, 1-30 mM) reduced the sustained component but did not affect ITO. In the presence of TEA and nifedipine, the voltage dependence of the steady-state inactivation data was well fitted by a Boltzmann distribution with a half-inactivation potential of -57 mV. The half-inactivation potential was shifted to a more positive potential in the presence of Cd2+ (-35 mV). The steady-state inactivation and activation data overlap between -50 and -30 mV, suggesting the presence of a "window" current in this potential range. In current-clamp mode, 4-AP depolarized single esophageal cells by approximately 8 mV and shifted the upstroke of the action potential to the left. These results indicate that, in the esophageal circular muscle, ITO is involved in the resting membrane potential and modulation of the onset of action potential.

4-Aminopyridine↗
PubMed1995

Involvement of K+ channels in the relaxant responses to various agonists in estrogen primed rat uterus.

The present investigation was undertaken to study the effects of K+ channel openers in the relaxant responses to various agonists in estrogen primed rat uterus. Adrenaline and isoprenaline produced a dose-dependent relaxation in the estrogen primed rat uterus. The relaxant responses were found to be significantly potentiated when the preparations were exposed to PSS devoid of calcium. The responses to isoprenaline were found to be greater in the preparations depolarized with 40 mM KCl instead of 80 mM KCl. KCl failed to produce any contractile effect in the presence of D-600. Further, the addition of D-600 completely relaxed the KCl depolarized rat uterus. Pinacidil and cromakalim failed to relax 80 mM KCl depolarized rat uterus. However, they produced dose-dependent relaxation in the preparations depolarized with 40 mM KCl. The relaxant responses to pinacidil and cromakalim were competitively blocked by procaine. However, they were not altered by either propranolol or cimetidine. The relaxant responses to isoprenaline and histamine were found to be potentiated by pinacidil and cromakalim. These results indicate that in rat uterus in addition to adenylate cyclase c-AMP, potassium channels are also involved in the relaxant responses to isoprenaline and histamine.

Animals↗
PubMed1995

Comparative effects of atenolol versus nifedipine on serum lipids and other biochemical parameters in diabetic and non-diabetic hypertensive subjects.

A controlled clinical trial on 65 patients was performed to compare the effects of nifedipine and atenolol in diabetic and non-diabetic hypertensive patients. Patients were from 45 to 70 years in age. The diabetic hypertensive patients and non-diabetic essential hypertensive patients randomly received atenolol (50-100 mg per day) or nifedipine (10-20 mg per day) for 9 months. Both the drugs effectively controlled the blood pressure throughout the therapy. Atenolol treatment significantly increased triglyceride levels and decreased the HDL-cholesterol levels after 9 months in both groups. However, nifedipine therapy did not alter lipid levels to any significant extent. Both drugs did not alter blood glucose, serum creatinine and blood urea levels. It may be concluded from the present study that nifedipine is preferable to atenolol as it does not alter lipid profile to any significant extent in diabetic and non-diabetic hypertensive patients.

Aged↗
PubMed1994

Prevalence of metaplasia at the gastro-oesophageal junction.

Specialised columnar epithelium (SCE), a form of intestinal metaplasia usually found in Barrett's oesophagus, cannot be distinguished endoscopically from normal gastric epithelium. Endoscopists seldom obtain biopsy specimens from a normal-appearing gastro-oesophageal junction, and therefore short segments of SCE in this region may go unrecognised. We studied patients who had short segments of SCE at the gastro-oesophageal junction. All patients scheduled for elective endoscopic examinations in our general endoscopy unit, irrespective of indication, were questioned for symptoms of gastro-oesophageal reflux disease. At endoscopy, severity of oesophagitis was graded, and biopsy specimens obtained from the squamocolumnar junction, irrespective of its appearance or location in the oesophagus. Among 142 patients without endoscopically apparent Barrett's oesophagus, 26 (18%) were found to have SCE. All patients with SCE were white, and the male/female ratio was 1.9. In contrast, non-whites accounted for 14% of the 114 patients without SCE and the male/female ratio was 0.8. The groups did not differ significantly in the frequency of symptoms and endoscopic signs of gastrooesophageal reflux. We conclude that adults frequently have unrecognised segments of SCE at the gastro-oesophageal junction; this may underlie the rising frequency of cancer of the gastrooesophageal junction in the USA and Europe.

Barrett Esophagus↗
PubMed1994

Innervation of the larynx, pharynx, and upper esophageal sphincter of the rat.

We identified a 'semicircular' compartment of the rat thyropharyngeus muscle at the pharyngoesophageal junction and used the glycogen depletion method to determine how the fibers of this muscle (as well as all others of the pharynx and larynx) are innervated by different cranial nerve branches. The semicircular compartment appears anatomically homologous to the human cricopharyngeus muscle, an important component of the upper esophageal sphincter. While we found very little overlap in the muscle targets of the pharyngeal, superior laryngeal and recurrent laryngeal nerves within the pharynx and larynx, the semicircular muscle receives a dual, interdigitating innervation from two vagal branches: the pharyngeal nerve and a branch of the superior laryngeal nerve we call the dorsal accessory branch. After applying horseradish peroxidase to either of these two nerves, we compared the distribution and number of cells labeled in the brainstem. The dorsal accessory branch conveys a more heterogeneous set of efferent fibers than does the pharyngeal nerve, including the axons of pharyngeal and esophageal motor neurons and parasympathetic preganglionic neurons. The observed distribution of labeled motor neurons in nucleus ambiguus also leads us to suggest that the semicircular compartment is innervated by two subsets of motor neurons, one of which is displaced ventrolateral to the main pharyngeal motor column. This arrangement raises the possibility of functional differences among semicircular compartment motor neurons correlated with the observed differences in brainstem location of cell bodies.

Animals↗
PubMed1994

Nitrinergic and peptidergic innervation of the human oesophagus.

The distribution, colocalisation, and interconnections of nitrinergic and peptidergic neurons and nerves in the human oesophagus were examined. Cryosections of surgically resected tissues from eight subjects were studied with indirect immunofluorescence for the presence of 11 neuropeptides and neuron specific enolase. After immunohistochemistry, nitric oxide synthase was shown on the same sections with the beta nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemical reaction. The histochemical findings were verified immunohistochemically on other sections with an antiserum against nitric oxide synthase. Most myenteric neurons (55%) were nitrinergic. Most (96%) received terminations positive for vasoactive intestinal polypeptide (VIP), calcitonin gene related peptide (CGRP) (80%), and galanin (59%). The neuronal somata of 14% also contained VIP, while 10% had galanin. Of the NADPH-diaphorase containing fibers seen in the muscle layers, many had closely associated VIP and galanin, but only rarely CGRP and substance P. Thus, despite abundant representation of both peptidergic and nitrinergic systems in oesophageal smooth muscle, only VIP and galanin colocalised to any significant extent with the nitrinergic elements. These findings provide morphological support for the role of nitric oxide as the non-adrenergic non-cholinergic inhibitory mediator in the human oesophagus and for its possible interactive role with the peptidergic system.

Adult↗
PubMed1994

Effect of sodium nitroprusside on Ca2+ currents in opossum esophageal circular muscle cells.

The effects of sodium nitroprusside (SNP) on ionic currents in single opossum esophageal circular muscle cells were examined. In voltage clamp, Ca2+ currents were studied after K+ currents were blocked with Cs+ in the patch pipette. The threshold for inward Ca2+ currents was -30 mV with peak current between 0 and +10 mV from holding potentials of -90 mV. The Ca2+ currents had both transient and sustained phases. The transient phase was partially resistant to nifedipine (1 microM). SNP (100 microM) reversibly decreased both the transient and sustained phases of the Ca2+ currents by approximately 20%. In cells dialyzed with high-K+ solutions, voltage-clamp recordings demonstrated the presence of an inward current followed by an outward current at potentials positive to -30 mV. SNP under these conditions resulted in a decrease in the Ca2+ current and decreased the outward current during test depolarizations. Action potentials were evoked during current-clamp recordings that consisted of multiple spikes, depending on the stimulus strength. The threshold for spike generation was close to -30 mV and was blocked by Cd2+, suggesting that the upstroke of the action potential was dependent on Ca2+ influx. SNP significantly attenuated action potentials and produced a small hyperpolarization (5-7 mV). These results suggest that SNP has a direct inhibitory effect on Ca2+ currents and thereby decreases evoked action potentials, and that SNP hyperpolarization is not due to Ca(2+)-activated K+ channels.

Action Potentials↗
PubMed1994

Evidence for catecholamine-depleting action of fluoxetine.

The present investigation was undertaken to study the interaction of fluoxetine with 5-hydroxytryptamine (5-HT) and noradrenaline (NA) in rat anococcygeus muscle and vas-deferens. In rat anococcygeus muscle responses to NA were significantly potentiated after 30 min and 60 min incubation with fluoxetine (2.9 x 10(-9) M). The responses to 5-HT were however, inhibited after 30 min incubation with fluoxetine in this preparation. On rat vas-deferens also, the responses to NA were potentiated after 30 min incubation with fluoxetine. The response to 5-HT were not altered significantly. In rats pretreated with fluoxetine (5 mg/kg, ip) for seven days, the responses to NA were significantly potentiated in rat anococcygeus muscle. Whereas the responses to 5-HT and tyramine were significantly inhibited. The inhibited responses to 5-HT restored back to normal when the anococcygeus muscle was pre-incubated with NA for 30 min.

Animals↗
PubMed1994

Hypozincemia in diabetes mellitus.

The present study was conducted on 20 age and sex matched healthy controls and 30 patients of diabetes mellitus. Serum zinc levels in diabetics were found to be significantly (p < 0.001) reduced as compared to healthy controls. There was no significant sex difference (P > 0.05) in serum zinc levels amongst diabetic patients and healthy controls. Hypozincema in diabetes mellitus may be due to altered zinc metabolism and oral zinc may have a role in therapy.

Adult↗
PubMed1993

The role of cricopharyngeus muscle in pharyngoesophageal disorders.

The cricopharyngeus muscle is generally thought to be responsible for the high pressure zone of the pharyngoesophageal (upper esophageal) sphincter. In this review we critically examined the evidence for the role of the cricopharyngeus muscle in the manometric pharyngoesophageal sphincter. The available studies show disparities between the anatomic location of the cricopharyngeus muscle and the manometric high pressure zone of the pharyngoesophageal sphincter. The cricopharyngeus muscle seems to correspond to the distal 1/3 of the sphincteric high pressure zone and the peak high pressure zone appears to be located proximal to the cricopharyngeus muscle. The discrepancy between the upper high pressure zone and the anatomic cricopharyngeus is important in understanding the role of the cricopharyngeus muscle in the pathophysiology and treatment of clinical disorders of the pharyngoesophageal sphincter.

Esophageal Diseases↗
PubMed1993

Nitric oxide involvement in the peptide VIP-associated inhibitory junction potential in the guinea-pig ileum.

1. Intracellular membrane potential recordings were made from circular smooth muscle cells of the guinea-pig ileum in the presence of atropine (1 microM) and nifedipine (0.1 microM) at 30 degrees C. 2. Electrical field stimulation with one or four pulses produced a fast inhibitory junction potential (IJP) which lasted around 1 s. It was abolished by tetrodotoxin (1 microM), apamin (0.3 microM), and alpha, beta-methylene ATP tachyphylaxis. 3. Nitric oxide synthase inhibitor N-nitro-L-arginine (L-NNA; 200 microM) had no effect on the resting membrane potential or the fast IJP. 4. Electrical field stimulation in the presence of apamin and substance P desensitization produced a slow IJP which was abolished by tetrodotoxin (1 microM). 5. L-NNA significantly reduced the amplitude of the slow IJP (P < 0.01). The antagonistic effect of L-NNA was reversed by L-arginine but not by D-arginine. 6. Injections of alpha, beta-methylene ATP, nitric oxide (NO), and vasoactive intestinal polypeptide (VIP) into the recording chamber caused tetrodotoxin-resistant hyperpolarizations of the smooth muscle membrane. Substance P desensitization did not modify the amplitudes of the hyperpolarizing response to ATP or NO, but increased the VIP hyperpolarization by 150% (P < 0.01). 7. L-NNA did not modify the amplitude of hyperpolarization due to ATP or NO; however, it antagonized VIP-induced hyperpolarization (P < 0.01). 8. These studies show that in the guinea-pig ileum circular muscle: (a) NO is not involved in the fast IJP which is mediated by ATP; (b) NO is involved in the slow IJP which is mediated by VIP and NO acting in series, and (c) the hyperpolarizing effects of VIP and the slow IJP are normally masked by overlapping depolarization due to concomitant release of substance P by the peptide VIP.

Animals↗
PubMed1993

Biphasic effect of SNP on opossum esophageal longitudinal muscle: involvement of cGMP and eicosanoids.

Effects of nitric oxide (NO)-containing compounds on opossum esophageal longitudinal smooth muscle in vitro were examined. Sodium nitroprusside (SNP) and authentic NO produced a biphasic concentration-dependent relaxation-contraction sequence in the esophageal longitudinal muscle (ELM) but only a concentration-dependent relaxation of the lower esophageal sphincter (LES) and no effect in the esophageal circular muscle. A cell membrane-permeable analogue of guanosine 3',5'-cyclic monophosphate (cGMP), 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) also produced relaxation-contraction sequence in the ELM and relaxation of the LES. The guanylate cyclase inhibitors methylene blue (MB) and LY-83583 increased resting tone and had no significant effect on SNP-induced relaxation of ELM. However, they abolished the SNP- and NO-induced contraction of ELM. The cyclooxygenase inhibitor indomethacin had no effect on ELM relaxation and abolished the contractions due to SNP, NO, and 8-BrcGMP. These studies show that in the ELM 1) SNP, authentic NO, and 8-BrcGMP cause a biphasic relaxation-contraction sequence; 2) MB and LY-83583 blocked contraction but not the relaxation associated with SNP and NO; and 3) indomethacin blocked contractions but not the relaxation due to SNP, NO, and 8-BrcGMP. These results suggest that in the ELM, NO donors exert an inhibitory action that is largely cGMP independent and an excitatory action via a cGMP-dependent pathway involving endogenous eicosanoids of the cyclooxygenase pathway.

Animals↗
PubMed1993

Effects of hydralazine on cardiac responsiveness to adrenergic agonists in streptozotocin-induced diabetic rats.

The present investigation was undertaken to study the effects of hydralazine treatment (50 mg/kg/day, p.o.) on methoxamine and isoproterenol-induced responses in cardiac preparations of control and streptozotocin (STZ)-induced diabetic rats. Triiodothyronine (T3) and thyroxine (T4) levels were found to be significantly decreased in diabetic rats and this decrease was prevented by hydralazine treatment. Methoxamine and isoproterenol produced a dose-dependent positive chronotropic and positive inotropic effect in right and left atrium respectively. These responses to methoxamine were significantly increased, whereas, those to isoproterenol were significantly decreased in preparations obtained from diabetic rats. Hydralazine treatment did not alter the isoproterenol-induced chronotropic effect in right atrium. However, it prevented the diabetes-induced increase in responsiveness to methoxamine in this preparation. Hydralazine increased significantly the inotropic response to methoxamine and isoproterenol in left atrium of control and diabetic rats. Both the pD2 value and maximum response were increased. The studies indicates that hydralazine-induced alterations in the responsiveness to methoxamine could partly be due to its ability to prevent diabetes-induced hypothyroidism. The effects of hydralazine on isoproterenol-induced responses appear to be independent of hypothyroidism, and some post-receptor mechanisms and metabolic derangements might be responsible for this effect.

Adrenergic Agonists↗
PubMed1992

Role of nitric oxide in esophageal peristalsis in the opossum.

To explore the involvement of NO in normal peristalsis, the effects of inhibitors of NO synthase, including N omega-nitro-L-arginine (L-NNA) and N omega-nitro-L-arginine methyl ester (L-NAME), on esophageal peristaltic contractions induced by diverse stimuli that may involve different neuronal circuits were studied. Studies were performed in opossums. Experimental conditions in vivo included primary peristalsis (P) induced by pharyngeal stroking, short-train (1 second) electrical stimulation of the vagus nerve which caused peristaltic (S) contractions, and long-train (10 second) electrical stimulation of the vagus nerves which caused contractions at the onset of (A contractions) and after (B contractions) the stimulation period. In vitro experiments were performed on strips of esophageal circular muscle using electrical field stimulation which caused contractions at the onset of (on contractions) and after (off contractions) the stimulation period. The administration of L-NAME significantly decreased the latency period and reduced the latency gradient for P contractions, thereby increasing the velocity of peristalsis. Concomitant administration of atropine prolonged the latency period but did not restore the latency gradient. L-NAME abolished B contractions in a dose-dependent fashion. In vitro, L-NAME caused dose-dependent inhibition of off contractions and augmentation of on contractions. These studies support the hypothesis that NO may be involved in (a) both the latency period and the latency gradient, as well as in the contraction amplitude of esophageal peristalsis; and (b) esophageal B and off contractions.

Animals↗
PubMed1992

Role of nitric oxide in lower esophageal sphincter relaxation to swallowing.

Studies were performed in the opossum to define the role of the L-arginine-nitric oxide (NO) pathway in lower esophageal sphincter (LES) relaxation to swallowing and vagal stimulation in viv and intramural nerve stimulation in vitro. In vivo, L-NAME, a water soluble NO synthase (NOS) inhibitor, caused antagonism of LES relaxation due to reflex-induced swallowing. L-NAME (20 mg/kg i.v.) reduced the amplitude of swallow induced relaxation from 88% to 28%. LES relaxation due to electrical stimulation of peripheral end of decentralized vagus nerve was also antagonized. The effects of L-NAME were reversed by L-arginine, but not by D-arginine. L-NAME treatment did not antagonize LES relaxation to intravenous administration of isoproterenol. In vitro, NO and sodium nitroprusside (SNP) caused a decrease in the sphincter tone. The relaxing effect caused by NO and SNP was not antagonized by tetrodotoxin or omega-conotoxin. Inhibitors of NO synthase, L-NMMA and L-NNA, caused slight increase in the spontaneous resting LES tone and concentration-dependent antagonism of electrical field stimulation (EFS) induced LES relaxation. L-NNA (10(-4)M) abolished EFS induced LES relaxation at low frequencies (less than 5 Hz) and antagonized the relaxation to a value 20% of the control at 20 Hz. The antagonistic action of L-NMMA and L-NNA was unaffected by D-arginine but was reversed by L-arginine. The inhibitory effect of NO, SNP, or two other putative inhibitory neurotransmitters (VIP and CGRP) on the LES was not antagonized by L-NNA. These studies show that inhibitors of NO synthase selectively antagonize LES relaxation to all three modes of intramural inhibitory nerve stimulation including physiological swallowing. These studies suggest that the L-arginine-nitric oxide pathway is involved in physiological relaxation of the LES.

Amino Acid Oxidoreductases↗