Ventricular nociception induced vesicular motility and urine flow: their relationship.

Heart acts as an important reflexogenic organ. Reflex urination and defaecation are two of the most important visceral symptoms observed in patients with myocardial ischaemia, infarction etc. In experimental animals also ventricular nociceptor stimulation by left anterior descending coronary artery (LAD) occlusion and nicotine application causes biphasic changes in urinary bladder movement and urine flow. Aim of the present study is to elucidate if there is any correlation between urine formation by the kidneys and movement of the urinary ladder under such experimental conditions. The experiments performed on intact cats show apparent coincidence of the two events. But, subsequent experiments following denervation of vagi and inferior cardiac nerve (ICN), spinal transaction and decerebration experiments indicate that these two are separate events. Further, experiments with different neurotransmitter blockers indicate that ventricular nocieptor induced urine formation and urinary bladder movements are two separate reflex responses and not dependent on each other.

The neural mechanism of rectal motility response induced by the epicardial application of lactic acid.

The epicardial application of lactic acid induced a biphasic rectal motility response in lightly anaesthetised, open-chested and artificially ventilated cats. This rectal biphasic response is reflexogenic in nature as epicardial lignocaine abolished such response. This rectal biphasic response is abolished by cardiac sympathectomy and reprecipitated by left inferior cardiac afferent nerve stimulation. Such response is also abolished by sacral ventral rhizotomy and reproduced by stimulation of the peripheral cut end of split sacral ventral roots. This indicates that the afferent and efferent pathways for such reflex are lying in the cardiac sympathetic and sacral pelvic nerves, respectively. The higher centers involved for such reflex are lying above the mid-collicular level of the brain as decerebration at the mid-collicular level completely abolished such type of rectal response. Furthermore, the relaxation phase and contraction phase of such rectal response are mediated through nitric oxide release and cholinergic neurones, respectively, as NG-nitro-L-arginine and atropine abolished relaxation and contraction phase of the rectal response, respectively.

Mitomycin C induced inhibition of adrenal steroidogenesis in female rats.

Mitomycin C (MC), an antibiotic which depresses DNA synthesis causes suppression of enzyme delta 5 3 beta-hydroxysteroid dehydrogenase (delta 5 3 beta OHD) and glucose-6 phosphate dehydrogenase (G-6 PD) in the rat adrenal tissue. The treatment resulted in a fall in DNA content together with an accumulation of cholesterol and ascorbic acid in the gland. The results suggest a diminution in adrenal steroid biogenesis similar to gonadal inhibition previously reported.

Calcium as a counteractive agent to streptomycin induced respiratory depression: an in vivo electrophysiological observation.

Effect of streptomycin on respiratory function in cats was studied. It was observed that streptomycin at a dose of 40 mg/kg body weight intravenously (i.v.) caused respiratory failure or streptomycin induced respiratory depression (SIRD). This respiratory failure is not linked with Herring-Breuer stretch receptors because the effect remained unaltered in artificially ventilated cats. The involvement of central structures in SIRD can be discarded since intracarotid and intraventricular administration of streptomycin failed to produce any change in respiration. Studies on monosynaptic reflex, dorsal and ventral root activities of spinal phrenic and intercostal nerves, and on fusimotor and alpha-motor neuron activities of spinal intercostal and phrenic nerves in decerebrated cats indicated clearly that respiratory depression is not only due to blockade at neuromuscular junction but due to functional depression at the level of muscle receptors and spinal cord motor neurons. The respiratory depression induced by streptomycin was more or less completely reversed when calcium was administered intravenously from external source. It is speculated that streptomycin induced respiratory depression may be mediated through calcium inhibition which can be treated with external calcium in conjunction with artificial respiration.

Effect of ATP on smooth muscle of toad urinary bladder.

Adenosine 5'-triphosphate (ATP), at a dose range of 1.8 to 116 microM, produced an initial phasic contraction followed by a rhythmic contraction in urinary bladder smooth muscle of the toad (Bufo melanostictus). Acetylcholine produced a rhythmic contraction which was antagonized by atropine (1.5 microM) and potentiated by neostigmine (1.7 microM), indicating activation of muscarinic receptors. However, both phasic and rhythmic components of ATP contraction were atropine-resistant. Quinidine (26-264 M) abolished the responses to ATP and acetylcholine, while indomethacin (28 microM) and theophylline (55 microM) antagonized only the acetylcholine responses. Repeated application of alpha, beta-methylene ATP desensitized the receptors and completely abolished contraction. ATP did not produce a phasic contraction in alpha, beta-methylene ATP-desensitized tissue, indicating that both ATP and its alpha, beta-methylene analogue occupy the same receptor site for phasic contraction. On the other hand, the rhythmic contraction induced by ATP remained unaffected in alpha, beta-methylene ATP-treated tissue. The phasic contraction in response to ATP can be blocked by verapamil (4 microM), but rhythmic contraction can only be abolished by a high concentration of verapamil (16 microM). Moreover, ATP produced no response in Ca+(+)-free or EGTA-containing solution, showing thereby that contractile responses to ATP are dependent upon extracellular Ca(+)+. These results indicate that the phasic component is a P2x-receptor-activated response while the rhythmic component might be an opening of calcium ion channels, either by depolarization of the membrane or by some unknown mechanism.

Effects of nicotine on spontaneous contractions of isolated atria of toad (Bufo melanostictus).

In toad atria, nicotine, at low concentrations (6.1 X 10(-6) M to 6.2 X 10(-5) M), produced a negative inotropic effect, and, at high concentrations (6.2 X 10(-4) M to 3.1 X 10(-3) M), a positive inotropic effect. The negative inotropism was potentiated by physostigmine or neostigmine and was antagonized by atropine or hemicholinium-3. The positive inotropism remained unaffected by exposure to phenoxybenzamine, phentolamine, propranolol, guanethidine, bretylium, hexamethonium, hemicholinium-3 or pretreatment with 6-OHDA or tyramine tachyphylaxis. The positive inotropism was antagonized by ethylene diamine tetraethyl acetate, verapamil or calcium-free Ringer. Caffeine induced positive inotropic effects, which were antagonized only by EDTA, and remained unaffected by exposure to verapamil or calcium-free Ringer. These results suggest a cholinergic mechanism for the negative inotropism produced by low concentrations of nicotine and also that the primary site of action of nicotine, when added at high concentrations, is the sarcolemmal calcium channel of toad atria resulting in increased calcium influx. They further suggest that the nicotine-induced positive inotropism is not mediated through activation of atrial adrenoceptors, ganglionic activation, presynaptic liberation of acetylcholine or liberation of catecholamine from sympathetic nerve endings.

Pharmacological and electrophysiological analysis of the effects of nicotine on cat blood pressure.

Nicotine (20-60 micrograms/kg) produced an initial vasodepressor response followed by a vasopressor response in anaesthetized cats, the mechanism of which was investigated. The vasodepressor response was antagonized by atropine or by vagotomy and was potentiated by physostigmine or neostigmine. Nicotine increased the single unit activity of different peripheral sympathetic nerves and evoked contraction of nictitating membrane and spleen along with vasopressor response. The vasopressor response was antagonized by phentolamine, prazosin, guanethidine, bretylium, 6-OHDA, hemicholinium-3 or hexamethonium. Propranolol or atenolol pretreatment potentiated the vasodepressor response and was antagonized by atropine. Desensitization by salbutamol did not modify the response to nicotine. The biphasic response to nicotine remained unaltered in yohimbine pretreated, in adrenalectomized, and in acute spinal as well as in decapitated animals; intracarotid or intracerebroventricular administration of nicotine did not produce any response. The biphasic response to nicotine does not involve the stimulation of the central vasomotor centre. In conclusion, these results suggest that the vasodepressor response is due to the vagal cholinergic mechanism. The vasopressor response is a consequence of activation of different peripheral adrenergic nerves causing increased release of the adrenergic transmitter at the neuroeffector region and the alpha 1-adrenoceptor mediate vasoconstriction in the systemic vascular bed.

Viscero-somatic reflexes following distension of urinary bladder in cats: role of supraspinal neuraxis.

Viscero-somatic reflexes have been studied by recording monosynaptic reflexes following distension of the urinary bladder in intact, decerebrate and spinal animals. It was observed that the viscero-somatic responses following bladder distension are inhibitory in nature and this inhibition was highest in decerebrates and least in spinal animals. The site of viscero-somatic interaction probably lies in the bulbar area (supraspinal) and spinal cord.

Sensory receptors and their afferents in the caudal sympathetic nerve of the domestic duck.

The behavioural reactivity of the visceral receptors and their afferents in the caudal sympathetic nerve (part of synsacral sympathetic chain) of domestic duck (Anas platyrhynchos) was studied using electrophysiological techniques to examine their involvement in different physiological functions. In total, 114 single unit activities were recorded from the caudal sympathetic nerve of duck. Receptors were classified according to location: in the anal sphincter (32 units), in the mucous membrane of the cloaca (45 units), at the branching point of the blood vessels over the rectum and adjacent mesentery (10 units), at the base of the feather follicles in and around the vent (17 units), and in the ventral and lateral lower abdominal wall muscle (10 units). Both spontaneous and non-spontaneous receptors responded to mechanical stimuli; average frequency of discharge of non-spontaneous units being much higher. Most of these receptors were of the rapidly-adapting type. Only some receptors in the abdominal muscle layer, anal sphincter and mucous membrane of hind gut were of the slowly-adapting type. Some of the latter responded to intraluminal distension pressure. Except for responses to succinylcholine chloride by receptors in the abdominal wall muscles and some units in the external anal sphincter, mechanosensitive receptors were not responsive to chemical stimuli. The discharge rate of the receptors at the base of the feather follicles varied according to the strength of stimulus. Conduction velocity of the caudal sympathetic afferent fibres ranged from 2.5 to 45 m/sec.

Positive inotropic effect of nicotine on electrically evoked contraction of isolated toad ventricle.

The mechanism of the responses of nicotine on electrically evoked contractions of the isolated spirally cut toad ventricle was investigated. Nicotine produced a concentration-dependent positive inotropic effect of the ventricle. Prior administration of propranolol, hexamethonium, hemicholinium-3 or guanethidine failed to antagonize the positive inotropic effect of nicotine, thus ruling out the possibility of the nicotine effect being mediated through activation of beta-adrenoceptors, ganglionic activation, presynaptic liberation of acetylcholine and liberation of norepinephrine from the sympathetic nerve endings respectively. The positive inotropic effect is probably mediated through mobilisation of calcium since prior incubation with verapamil--the calcium transport blocker, EDTA, which chelates the extracellular calcium and calcium-free Ringer prevented the positive inotropic effect of nicotine. These results suggest that the positive intropic effect of nicotine may presumably be due to the facilitating effects of nicotine on Ca++ exchange or mobilisation of membrane bound Ca++.

Visceral receptors and their afferents in the caudal mesenteric nerve of the duck.

1. The behaviour and reactivities of visceral receptors to different mechanical and chemical stimuli in simple unit preparations from the caudal mesenteric nerve of adult ducks were studied to examine the physiological roles of such receptors. 2. In total, 83 single unit activities were recorded from the caudal mesenteric nerve. 3. Receptors were grouped according to their locations in different layers of the rectum as (i) over the branching points of the blood vessel or in the serosal layer, (ii) in the muscle layer or (iii) in the mucous membrane of the rectum. 4. All the receptors, both spontaneous and non-spontaneous, responded to mechanical probing. Receptors of the muscle layer responded to distension also and showed a slowly-adapting nature. Most of the receptors of the other two groups were of the rapidly-adapting type. 5. Conduction velocity ranged from 0.76 to 34.6 m/s. 6. Sympathetic afferent fibres from the hind gut ascend along the intestinal nerve and join the caudal mesenteric nerve via the colonic ganglion.

The distribution in the cat brain stem of neurones activated by vagal nonmyelinated fibres from the heart and lungs.

In anaesthetized cats, right cardiac vagal branches were electrically stimulated and recordings of evoked 'slow wave' and single neurone activity were made in the brain stem. Short-latency 'slow wave' and multi-neuronal activity evoked by excitation of myelinated vagal afferent fibres were recorded in the medial and lateral subnuclei of the nucleus tractus solitarius, the area postrema, the dorsal vagal motor nucleus, the lateral reticular formation and the nucleus ambiguus. Long-latency responses evoked by vagal non-myelinated fibres were recorded in the medial subnucleus of the nucleus tractus solitarius, the area postrema, dorsal vagal motor nucleus, the parahypoglossal area and the lateral reticular formation dorsal to the nucleus ambiguus. A specific study was made of seventy-two single neurones activated by non-myelinated afferent fibres in the cardiac branch. Thirty-four were shown to be synaptically activated, twenty-one were activated nonsynaptically and seventeen could not be classified. One neurone was also activated by myelinated cardiac afferent fibres, and two by thoracic vagal (including pulmonary) afferent fibres. Neurones were not spontaneously active. Indirect evidence suggests that the majority of the recordings of nonsynaptically activated neurones were likely to be from cell bodies. Neurones were located from the level of the obex to 3.0 mm rostral to it in the medial subnucleus of the nucleus tractus solitarius (45), and in the lateral subnucleus (2), the area postrema and its border with the medial subnucleus of the nucleus tractus solitarius (13), the dorsal vagal motor nucleus (9), the parahypoglossal area (1) and the lateral reticular formation dorsal to nucleus ambiguus (2). Recordings were made from fifteen neurones activated by myelinated fibres in the cardiac vagal branches, and twelve were excited synaptically. The neurones were located in the medial (8) and lateral (3) subnuclei of the nucleus tractus solitarius, the dorsal vagal motor nucleus (1) and the lateral reticular formation (1). Four neurones were also excited by vagal afferent fibres in the thoracic vagal nerve immediately caudal to the caudal cardiac branch.