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Biomedical subjects

K Sundaram

Publications and source records attributed to K Sundaram.

At least 55 records · Page 3Linked to original sources
PubMed1990

Relative effects of different spinal autonomic nuclei on cardiac sympathoexcitatory function.

Mean arterial pressure and heart rate were monitored in immobilized and artificially ventilated male Wistar rats either anesthetized with pentobarbital or decerebrated at midcollicular level. The rate of increase in the left ventricular pressure was also monitored in order to compute contractility index. L-glutamate (1.77 nmole) was microinjected (10 nl) into the following autonomic nuclei of the spinal cord at C8 to T4 levels: 1) intermediolateral column (IML), 2) n. intercalatus spinalis (IC) and 3) n. intercalatus pars paraependymalis (ICpe); this region is commonly known as the central autonomic area (CA). The site of microinjection was marked by injection of a dye; these studies suggested that microinjections of glutamate into the IML are likely to encompass the neurons in the nucleus (n.) intermediolateralis thoracolumbalis pars principalis (ILp) and n. intermediolateralis thoracolumbalis pars funicularis (ILf). Sympathoexcitatory cardiac responses to glutamate microinjections were elicited from T1 to T3 levels; these responses could not be evoked at C8 and T4 levels. In each of these segments, maximum responses were obtained from the IML while the responses evoked from the IC and the CA were minimal. These results suggest that at T1 to T3 levels of the spinal cord, IML is the main cell group regulating sympathetic cardiac function; CA and IC may play a relatively minor role in this function.

Adrenergic Fibers↗
PubMed1990

Allosensitization induced suppression of various murine tumors: role of non-H-2 antigens in antitumor immunity.

Presence of alloantigens on various murine tumors was tested by tumor rejection in allosensitized Swiss mice. The results indicated the presence of alloantigen on immunogenic tumors like chemically induced fibrosarcoma (FS), ascitic sarcoma 180 (S 180) and immunogenic variant of lymphosarcoma (LS-A) in Swiss mice, while these antigens could not be detected by this procedure on spontaneous lymphosarcoma (LS). Allosensitization with skin graft was found to offer quantitatively higher antitumor resistance than the allosensitization achieved by allogeneic lymphocytes. Antitumor effect was not seen when tumor cells were inoculated earlier than day 3 of grafting. Further, host immunosuppression with whole body irradiation up to day of 3 of skin grafting abrogated the antitumor effect. H-2 compatible and non-H-2 incompatible skin graft sensitization of host could offer resistance against both S 180 and LS-A. Further, tumor immune mice rejected H-2 compatible, non-H-2 incompatible skin graft significantly earlier.

Animals↗
PubMed1989

Microinjections of cholinergic agonists into the intermediolateral cell column of the spinal cord at T1-T3 increase heart rate and contractility.

Cardiovascular responses to the microinjections of cholinergic agonists into the intermediolateral cell column (IML) of the spinal cord at T1-T3 level were studied. Mean arterial pressure (MAP), heart rate (HR), the rate of increase in the left ventricular pressure (dp/dt) and contractility index (CI) were monitored in immobilized and artificially ventilated male Wistar rats either anesthetized with pentobarbital or decerebrated at mid-collicular level. Microinjections (20 nl) of carbachol (110-660 pmol) into the right IML elicited a marked increase in HR and a small increase in CI. A marked increase in the CI with relatively little effect on the HR was observed when carbachol was injected into the left IML. The cardioacceleratory effects of carbachol, but not those of L-glutamate, were blocked by prior microinjections of scopolamine (18 nmol) into the IML. Intravenous injections of chlorisondamine (a ganglion blocker) also blocked these effects of carbachol. Spinal transections at C4 or T6 level did not alter these responses. Microinjections of acetylcholine (0.01-1 nmol) into the right IML also produced tachycardic effects. The responses to acetylcholine were blocked by prior injections of a muscarinic receptor blocker (atropine hemisulfate, 0.2 nmol). Microinjections of a selective M2 muscarinic receptor agonist, cis-methyldioxolane (CD; 0.2-0.8 nmol), but not those of a relatively selective M1 receptor agonist (McN-A343; 2-3 nmol), into the right IML elicited an increase in HR. Previous microinjections of a selective competitive M2 receptor antagonist (AFDX-116; 0.8 nmol), but not those of a potent selective M1 receptor antagonist (pirenzepine; 2 nmol), into the IML blocked the effects of CD. Nicotine (0.25-1 nmol) when injected into the right IML also produced positive chronotropic effects. These responses were blocked by prior microinjections of hexamethonium (5 nmol). The above-mentioned results suggest that cholinoceptive neurons, interneurons or terminals are located in the areas of IML which control cardiac functions. Muscarinic as well as nicotinic receptors are present in this area. Muscarinic receptors are predominantly of the M2 type. The physiological significance of the presence of cholinergic receptors in this area in controlling cardiac functions remains to be established.

Acetylcholine↗
PubMed1989

Cholinergic mechanisms in the ventrolateral medullary depressor area.

Cardiovascular actions of cholinergic agonists in the ventrolateral medullary depressor area (VLDA) were investigated. Microinjections (0.2-1.6 nmol/site) of an M2 muscarinic receptor agonist (cis-methyldioxolane; CD) into the VLDA decreased blood pressure (33-71 mm Hg) and heart rate (11-62 beats/min). Microinjections of AFDX-116 (a specific blocker for M2 receptors), but not those of pirenzepine (a specific blocker for M1 receptors), prevented the depressor responses induced by CD. Unilateral microinjections of CD (0.3 nmol) into the VLDA also elicited depressor and bradycardic effects which were blocked by microinjections of bicuculline methiodide (200 pmol) into the ipsilateral ventrolateral medullary pressor area (VLPA). Bilateral vagotomy did not alter the depressor and bradycardic actions of CD in the VLDA. McN-A343 (2-3 nmol/site), an M1 receptor agonist, failed to evoke any response when microinjected into the VLDA. These results indicate that muscarinic receptors of the M2 type are present in the VLDA. Activation of the latter by cholinergic agonists results in depressor and bradycardic responses. These responses are mediated via the VLPA.

Animals↗
PubMed1989

Electrolytic lesions in the depressor area of the ventrolateral medulla of the rat abolish depressor responses to the aortic nerve stimulation.

The pressor (VLPA) and the depressor (VLDA) areas in the ventrolateral medulla were identified with the microinjections of L-glutamate (1.77 nmol/site) in artificially ventilated, pentobarbital-anesthetized male Wistar rats. Electrical stimulation of the left or right aortic nerve (1-6 V, 10-40 pulses/s, 3 ms) produced usual depressor responses. Electrolytic lesions (2.5 mA for 30 s) were placed bilaterally in the VLDA. Lack of responses to subsequent microinjections of glutamate into the VLDA indicated that the lesions were complete. The function of the VLPA was not compromised because it continued to respond to microinjections of glutamate. Subsequent stimulation of the aortic nerves failed to elicit the usual depressor responses. These results confirm our earlier reports indicating that the VLDA is important in mediating the depressor component of the aortic baroreflex.

Animals↗
PubMed1989

Cardiac responses to the microinjections of excitatory amino acids into the intermediolateral cell column of the rat spinal cord.

Sympathoexcitatory cardiovascular responses to the microinjections of L-glutamate into the intermediolateral cell column (IML) of the upper thoracic cord (C8 to T4) were studied. Mean arterial pressure (MAP), heart rate (HR), the rate of increase in the left ventricular pressure (dP/dt) and contractility index were monitored in immobilized and artificially ventilated male Wistar rats anesthetized with pentobarbital or isoflurane. On the right side, microinjections (10-20 nl) of L-glutamate (0.9-1.77 nmol in 0.9% sodium chloride solution, pH 7.4) into the IML at T2 level produced marked tachycardiac responses with relatively small changes in contractility. On the left side, similar microinjections produced marked increase in dP/dt and contractility index with relatively small increase in HR. On either side, the responses were smaller at T1 and T3 level and absent at C8 and T4 level. No changes in blood pressure were observed with microinjections of L-glutamate on either side. Microinjections of N-methyl-D-aspartic acid (NMDA), 1-100 pmol, into the IML elicited responses similar to those of L-glutamate. These amino acids failed to evoke any response when microinjected into the adjacent areas (e.g. 0.5 mm lateral or medial to the IML). The effects of glutamate and NMDA in the IML were blocked by microinjections of glutamic acid diethylester (GDEE) and D-2-amino-7-phosphonoheptanoic acid (D-AP7), respectively. Control microinjections of physiological saline into the IML produced no responses. These results indicate that excitatory amino acids, in small doses and volumes, can be used to identify cardiac sympathoexcitatory neuronal pools in the IML. This preparation may prove useful in characterizing pharmacological actions of various putative neurotransmitters in this region of the spinal cord.

Animals↗
PubMed1989

M2 muscarinic receptor agonists produce hypotension and bradycardia when injected into the nucleus tractus solitarii.

Bilateral microinjections (0.2-2 nmol/site) of a potent M2 muscarinic receptor agonist, cis-methyldioxolane (CD), but not those of a relatively selective M1 receptor agonist (McN-A343; 3 nmol/site), into the intermediate portion of nucleus tractus solitarii (NTS) of pentobarbital-anesthetized rats elicited a decrease in blood pressure (23-52 mm Hg) and heart rate (16-50 bpm). Previous microinjections of a selective competitive M2 receptor antagonist (AFDX-116; 0.8 nmol/site), but not those of a potent selective M1 receptor antagonist (pirenzepine; 2 nmol/site), into the NTS blocked the effects of CD. These results indicate that the muscarinic receptors in the intermediate portion of NTS are of M2 type.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1989

Radium-226 retention in placenta and whole body of rat. Preliminary studies.

The 226Ra retention in the placenta of rat during 3 successive pregnancies (92-213 days after injection) was about 4-5 x 10(-3)% of the injected dose (ID) constituting nearly 0.009% of the whole body 226Ra content (45-55% ID) in each pregnancy. Thus a uniform relationship was being displayed between the two contents to a reasonable extent. The implication of this observation is discussed vis-a-vis the determination of Ra body burden.

Animals↗
PubMed1988

M2 muscarinic receptors mediate pressor responses to cholinergic agonists in the ventrolateral medullary pressor area.

Microinjections of cholinergic agonists into the ventrolateral medullary pressor area (VLPA) evoke increase in blood pressure (BP) and heart rate (HR). Recently two major subtypes of muscarinic receptors (M1 and M2) have been identified. This investigation was designed to study the role of these muscarinic receptor subtypes in pressor responses of cholinergic agonists in the VLPA. Male Wistar rats were anesthetized with pentobarbital or decerebrated at mid-collicular level. The rats were artificially ventilated and BP and HR were recorded. Ventral medulla was exposed and the VLPA identified bilaterally by microinjections of L-glutamate. Microinjections of cis-methyldioxolane (CD, a specific agonist of M2 receptors) in the doses of 0.004-4 nanomol (nmol)/site into the VLPA evoked an increase in BP (13-56 mm Hg) and HR (7-24 bpm) which lasted for 10-50 min. Intravenous injections of the same doses of this agent failed to evoke a response. AFDX-116 (a specific M2 muscarinic receptor antagonist) microinjected into the VLPA (0.2-1.6 nmol-/site) evoked depressor responses (6-20 mm Hg). Microinjections of this agent into the VLPA prevented the pressor responses to subsequent microinjections of CD at the same sites, indicating that AFDX-116 blocked M2 receptors. AFDX-116 rendered neurons in the VLPA unresponsive to L-glutamate but this effect lasted for 30-40 min while the hypotensive and M2 receptor blocking effect lasted for 60-150 min. McN-A343 (a specific agonist for M1 receptors) or pirenzepine (PZ, a specific antagonist of M1 receptors) injected into the VLPA (0.4-4 nmol/site) failed to evoke any response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Antagonists of luteinizing hormone releasing hormone bind to rat mast cells and induce histamine release.

It was reported previously that administration of certain synthetic antagonists of LHRH to rats produced allergy-like symptoms that were attributed to their histamine releasing action. In the present study the interaction of LHRH analogs with rat peritoneal mast cells was investigated in vitro. Potent antagonists of LHRH showed strong in vitro histamine releasing activity from rat peritoneal mast cells. Membrane preparations of rat pituitary glands showed specific binding of radioiodinated LHRH antagonist as well as LHRH agonist. However, rat peritoneal mast cells and membrane preparations from those cells bound antagonist but not the agonist. Furthermore, the LHRH antagonist did not bind to membranes prepared from tissues such as prostate, liver, kidney, and brain. Competitive displacement curves of the [125I]-antagonist with different LHRH analogs showed that the ability of the analogs to compete for binding sites on mast cells was related to their histamine releasing activity. We conclude that histamine release from rat mast cells induced by LHRH analogs is mediated by specific binding of the active peptides to cell membranes. Furthermore, using rat mast cells, the binding assay in conjunction with histamine releasing assay may be utilized to predict the in vivo histamine releasing potential of new LHRH peptides which are of clinical importance.

Animals↗
PubMed1988

Effect of sulfasalazine and its analogs on fertility in male rats.

Several derivatives of sulfasalazine were tested for their antifertility activity in male rats. The compounds were administered to groups of rats daily by oral gavage for 28 days. Fertility of the rats treated with sulfasalazine or compound CH 74A was reduced, while other compounds had no effect. In a subsequent experiment, therefore, only the active compounds were studied further. Fertility of rats treated with sulfasalazine, compound CH 74A, CH 99A or sulfapyridine was reduced during 40 days of treatment. At the end of treatment, body weights were reduced in higher dose groups of sulfasalazine, CH 74A and sulfapyridine compared to control animals. The weights of the testes, prostate or seminal vesicle were not altered by any of the treatments. On the other hand, weight of the epididymides decreased in all higher dose groups except in CH 99A-treated animals. Sperm motility decreased in all the treated rats except in animals treated with low dose of sulfapyridine, whereas epididymal sperm count decreased in all but CH 99A-treated animals. These results suggest that sulfasalazine and its derivatives bring about their antifertility effects by decreasing sperm motility and/or number of spermatozoa.

Animals↗
PubMed1988

Cholinergic nerve terminals in the ventrolateral medullary pressor area: pharmacological evidence.

This investigation was designed to demonstrate the presence of cholinergic nerve terminals in the pressor area of the ventrolateral medulla (VLPA) and to study the effects of the release of endogenous acetylcholine in this area. Bilateral microinjections (0.1-2 nmol)/site) of 3,4-diaminopyridine (DAP), which releases acetylcholine from cholinergic nerve terminals, into the VLPA in anesthetized rats evoked an increase in blood pressure and heart rate which lasted for 20-40 min. Intravenous injections of the same doses of this agent failed to evoke a response. The ganglion blocker, chlorisondamine (3 mg/kg, i.v.) abolished the responses to microinjections of DAP indicating that the responses were mediated by the sympathetic nervous system. Microinjections of scopolamine or a specific M2 muscarinic receptor antagonist (AFDX-116) into the VLPA prevented the pressor and tachycardic responses to subsequent microinjections of DAP at the same sites indicating that the responses were mediated via M2 receptors. Microinjections of hemicholinium (3 nmol/site; which impairs acetylcholine synthesis) attenuated the responses to the subsequent microinjections of DAP at the same sites. These results indicate that the substance released from the terminals in the VLPA may be predominantly acetylcholine which evokes pressor and tachycardic responses via M2 muscarinic receptors. The origin and physiological significance of these cholinergic terminals in the VLPA are not known.

4-Aminopyridine↗
PubMed1988

Sertoli cell-only syndrome produced by cold testicular ischemia.

This report describes a new method for producing Sertoli cell-only testes in the Lewis rat using 90 min of hypothermic testicular ischemia. The method employs selective occlusion of the testicular blood supply using atraumatic microclips applied with the aid of an operating microscope. The testis is packed in ice-cold saline throughout the ischemic interval, and the deferential artery and vein are ligated. Twelve weeks after the ischemic insult, the testes weigh half that of control testes while there were no differences in prostate or seminal vesicle weights. Microscopic examination of the ischemic damaged testes revealed normal-appearing Leydig and Sertoli cells, but complete absence of germ cells. Assays of testicular enzyme activities indicated that lactic dehydrogenase and sorbitol dehydrogenase were reduced, while alpha-glutamyl transpeptidase activity was normal, consistent with the marked reduction of germ cells. Serum androgen binding protein (rABP) levels were elevated relative to nonischemic controls. By contrast, serum concentrations of testosterone, LH, and FSH were normal. In addition, LHRH elicited identical LH and testosterone responses in control and experimental animals. Testicular blood flow measured with 133Xenon was slightly decreased in Sertoli-cell-only testes. Intratesticular temperatures was normal in all groups. These observations in rats with ischemia-induced Sertoli-cell-only testes are strikingly different from those induced by radiation or genetic defects. Animals with these latter disorders have elevated FSH levels, evidence of altered Leydig cell function as evidenced by elevated LH or abnormal response to LHRH; and normal or low serum rABP levels. We conclude that 1) ischemia produces no abnormalities of the pituitary testicular axis in spite of marked germ cell depletion and 2) Sertoli-cell-only testes of different etiologies can have varied patterns of hormone and rABP secretion.

Androgen-Binding Protein↗
PubMed1987

Arachidonic acid is involved in the regulation of hCG induced steroidogenesis in rat Leydig cells.

Phospholipase C (PLC), an enzyme involved in the hydrolysis of membrane phospholipid- phosphatidylinositol-bisphosphate to inositol triphosphate and diacylglycerol, and Phorbol 12, myristate 13, acetate (PMA), a tumor promoting agent, could significantly stimulate testosterone (T) secretion from Leydig cells. Arachidonic acid (AA) stimulated T secretion by about 2 fold. The steroidogenic effect of PLC and AA was biphasic. At low concentrations both PLC and AA (100 mU and 12.5 microM, respectively) augmented hCG induced T secretion, while at higher concentrations (PLC: 500 mU and AA: 200 microM) they inhibited steroid production. AA also had a biphasic effect on hCG induced cyclic AMP secretion. 5, 8, 11, 14 Eicosatetraynoic acid (ETYA), a general inhibitor of AA metabolism, and Nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase pathway of AA metabolism, inhibited hCG induced T secretion while indomethacin, an inhibitor of cyclo-oxygenase pathway, had no effect on hCG induced T secretion. We conclude from these data that AA plays a role in the regulation of hCG induced steroidogenic responses in rat Leydig cells and that the metabolite(s) of AA that are involved are not cyclooxygenase products.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1987

Long-term immunization against the beta-subunit of ovine luteinizing hormone (oLH beta) has no adverse effects on pituitary function in rhesus monkeys.

One postulated safety hazard of contraceptive methods based on immunization against gonadotropic hormones is the possibility that circulating antibodies which crossreact with pituitary hormones may impair pituitary function through the deposition of immunoglobulin and/or complement suggesting immune complexes. In order to evaluate this possibility in rhesus monkeys actively immunized against the beta-subunit of ovine luteinizing hormone (oLH beta), we used three approaches to study the effects of long-term immunization on pituitary function: a) evaluation of pituitary responsiveness to challenge with a GnRH-agonist; b) examination of pituitary histology and immunostaining with gonadotropin antisera; and c) examination of pituitary cells for deposition of immune complexes. Our results indicate that circulating anti-oLH beta antibodies did not result in significant impairment of pituitary function in rhesus monkeys.

Animals↗