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Biomedical subjects

A Saria

Publications and source records attributed to A Saria.

At least 163 records · Page 9Linked to original sources

The effect of nephrectomy and ureter ligation on plasma neurotensin-like immunoreactivity levels in the conscious rat.

The effect of nephrectomy and ureter ligation on the concentration of endogenous plasma neurotensin-like immunoreactivity (p-NTLI) was studied in conscious rats by means of antiserum 17-8201 which detects NT (1-13) only, and antiserum 0-7709 which detects NT(1-13) and NT(1-8). The unstimulated p-NTLI concentration did not change significantly during a 25-h observation period following nephrectomy in comparison with sham operation. However, stimulation of the release of NTLI by intraduodenal administration of oleic acid (0.2 ml) resulted in significantly higher p-NTLI levels in the nephrectomized rats than in the sham operated rats. Ureter ligation did not significantly affect basal or stimulated p-NTLI. The data indicate that the kidneys play an important part in the elimination of p-NTLI released after fat ingestion.

Animals↗

Evidence for substance P-immunoreactive spinal afferents that mediate bronchoconstriction.

The origin and functional role of capsaicin-sensitive substance P-(SP-) immunoreactive (IR) nerve fibres in the lower airways were studied in the guinea-pig. Stellatectomy caused a significant reduction of SP-IR in the lung and pulmonary artery. Immunohistochemical analysis, however, did not reveal any clear-cut change in the number and distribution of SP-IR fibres in the lung of these animals. After combined stellatectomy plus local capsaicin treatment of the vagal nerves, most SP-IR nerves disappeared in the lower airways. The bronchoconstriction induced by capsaicin was significantly reduced after stellatectomy and abolished after stellatectomy plus capsaicin pretreatment of the vagal nerves. Ether inhalation caused bronchoconstriction, which was not influenced by stellatectomy but markedly reduced by combined capsaicin treatment of vagal nerves and stellatectomy. Stellate ganglion stimulation in animals that had been chemically sympathectomized by 6-OH-dopamine caused bronchoconstriction, which was resistant to cholinergic or adrenergic receptor blockade. This response was absent after systemic capsaicin pretreatment, suggesting that it was due to antidromic stimulation of afferent fibres traversing the stellate ganglion. In conclusion, the present data suggest that the lower airways receive SP-IR capsaicin-sensitive C-fibre afferents of both vagal and spinal origin. These sensory fibres seem to have branches both within the bronchial smooth muscle and around blood vessels.

Afferent Pathways↗

Substance P-immunoreactive sensory nerves in the lower respiratory tract of various mammals including man.

The occurrence and origin of substance P (SP)-immunoreactive (IR) nerves in the lower respiratory tract was studied by means of immunohistochemistry in the guinea-pig, rat, cat and man. In addition, biopsies from human material were also analysed by radioimmunoassay. SP-IR nerves were seen in four principal locations: 1) under or within the lining epithelium, 2) around blood vessels, 3) within the bronchial smooth muscle layer, and 4) around local tracheobronchial ganglion cells. Ligation experiments combined with capsaicin pretreatments indicated that all SP-IR nerves in the respiratory tract are sensory. The trachea seems to be mainly supplied by the vagal nerves, while intrapulmonary bronchi and blood vessels receive SP-IR nerves of both vagal and non-vagal (spinal) origin. SP-IR nerves were also found in the human bronchi with principally similar location as in the guinea-pig. The levels of SP-IR in the trachea and peripheral bronchi of man were about 3-4 pmol/g, which is in the same range as the content of corresponding tissues from the guinea-pig. In conclusion, the present experimental findings of SP-IR nerves in the lower respiratory tract in both experimental animals and man support the functional evidence for the importance of SP in the vagal and non-vagal (spinal) control of bronchial smooth muscle tone and vascular permeability.

Adult↗

Substance P immunoreactivity in the rat mammary nipple and the effects of capsaicin treatment on lactation.

Tissue concentrations of substance P immunoreactivity (SP-I) were measured in rat mammary nipples and were significantly greater than in ventral abdominal skin in nonpregnant and pregnant rats. In contrast, the concentration of nipple SP-I was lower than that of skin in twelve day lactating animals. The mean total SP-I content of the pooled twelve nipples from each rat was not significantly different in nonpregnant, pregnant or lactating rats. However, the mean weight of the pooled twelve nipples from each rat was significantly higher in the lactating rats than in pregnant rats. Immunohistochemistry revealed SP-I nerve trunks and single fibers throughout the nipples of lactating rats. Nerve fibers were observed among smooth muscle and along blood vessels throughout the dermis and in association with epidermal structures. Some SP-I fibers were also observed in association with the main lactiferous duct and mammary gland secretory parenchyma. Radioimmunoassay and immunohistochemistry of nipples from lactating rats treated with capsaicin as neonates revealed a marked depletion of SP-I. Rats treated with capsaicin as neonates had a normal gestation period and produced litters of normal size and birth weight. However, the litters of these lactating rats grew at a significantly slower rate than litters from controls. The quantity of milk obtained from capsaicin-treated lactating dams, following a one hour suckling period on the twelfth day of lactation, was significantly less than that obtained by litters of control dams. It is concluded that capsaicin-sensitive primary sensory nerves of the mammary nipple play a role in the afferent limb of the suckling reflex. One transmitter candidate for these nerves is substance P.

Animals↗

Inhibition of compound 48/80--induced vascular protein leakage by pretreatment with capsaicin and a substance P antagonist.

Intravenous injection of compound 48/80 (1 mg X kg-1) induced an acute increase in vascular permeability to plasma proteins in various organs of rats. The compound 48/80 response was partly inhibited by histamine H1 and H2 receptor blockade in the urinary bladder and in the duodenum, but not in the trachea, the oesophagus, the ureter and the paw skin. Blockade of 5-hydroxytryptamine receptors with methysergide led to a reduction of the permeability response in the oesophagus and in the urinary bladder, leaving responses in other organs unchanged. Pretreatment of neonatal rats with capsaicin almost abolished the 48/80 response in all organs except in the duodenum. Pretreatment of rats with [D-Arg1, D-Trp7,9, Leu11]-substance P, a substance P antagonist, also caused a partial inhibition of the permeability response to compound 48/80 in several organs. Topical administration of compound 48/80 (1 mg X ml-1) onto the tracheal mucosa induced local Evans blue extravasation. This response was resistant to pretreatment with histamine receptor antagonists, but was largely inhibited after neonatal capsaicin pretreatment. Topical administration of compound 48/80 (1 mg X ml-1 or 10 mg X ml-1) into the eye did not cause visible Evans blue extravasation in the conjunctiva, nor any signs of pain reaction as indicated by the absence of the wiping response, usually seen upon noxious chemical stimuli in the eye. In guinea-pigs, 10 mg X kg-1 compound 48/80 i.v. were required to induce vascular protein leakage in different organs. This response was blocked by pretreatment with H1 and H2 receptor antagonists, but only slightly reduced after systemic capsaicin pretreatment of guinea-pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Substance P in primary afferent neurons of the female rat reproductive system.

The amount of substance P-immunoreactivity (SP-I) was studied in the female rat reproductive organs (uterus, cervix, vagina and ovary) in the diestrous and estrous stages of the estrous cycle, after ovariectomy and on days 7, 14 and 19 of pregnancy. The concentration of SP-I (pmol X g-1 tissue) was generally highest in the vagina followed by cervix, uterus and ovary. SP-I concentrations in all reproductive organs were significantly higher following ovariectomy but significantly lower during pregnancy compared to concentrations from intact rats. There were no significant differences in the total content of SP-I per organ during the estrous cycle, after ovariectomy or during pregnancy (cervix, vagina). SP-I concentrations were markedly reduced in the reproductive organs of adult rats treated with capsaicin as neonates. This led to the conclusion that SP in reproductive organs is present in primary afferent fibers. The findings indicate that the number of SP-I containing primary afferent fibers in the female reproductive organs are stable elements neither increasing nor decreasing in response to changing hormonal levels or to the tissue growth and differentiation occurring during the estrous cycle or pregnancy.

Animals↗

The effects of neonatal capsaicin treatment on growth and subsequent reproductive function in the rat.

The results of the present study describe the following effects of neonatal capsaicin treatment on growth and reproductive function in the rat. Neonatal capsaicin treatment in the rat resulted in a retardation of body growth through adulthood most pronounced at 35 days of age. Capsaicin-treated rats had normal estrous cycles, but mated significantly less frequently than age-matched controls. Confirmed matings in capsaicin-treated female rats resulted in significantly fewer pregnancies compared to controls. Male rats treated with capsaicin as neonates produced significantly fewer pregnancies when mated with untreated females compared to controls. Ovulation, sperm transport, and fertilization occur normally in capsaicin-treated rats. The decidual response was markedly diminished in mated capsaicin-treated rats. These findings led to the conclusion that the neurohormonal reflex, which is normally initiated through the stimulation of the cervix by copulation, and which ultimately stimulates secretion of pituitary luteotropic hormones, did not occur in capsaicin-treated rats. Thus, ovarian progesterone secretion was not facilitated resulting in inadequate hormonal support for implantation, pregnancy or pseudo-pregnancy. These data further suggest that the sensory limb of this neurohormonal reflex may consist of capsaicin-sensitive, possibly substance P containing, primary afferent fibers.

Animals↗

Capsaicin pretreatment inhibits vagal cholinergic and non-cholinergic control of pulmonary mechanics in the guinea pig.

The effects of vagal nerve stimulation, ether, capsaicin, histamine and substance P (SP) on lung resistance (RL) and dynamic lung compliance (CDYN) were studied in anaesthetized guinea pigs. The in vivo responses in control animals were compared with the effects after systemic pretreatment with capsaicin or local application of capsaicin on the cervical vagal nerves. Vagal nerve stimulation induced an increase in RL and a fall in CDYN. Significant changes in RL and CDYN (more than 50%) were still present after atropine, while the vagal heart response was abolished. Systemic or local capsaicin pretreatment abolished the atropine-resistant vagal effect on RL and CDYN. The atropine-sensitive changes in pulmonary mechanics upon vagal stimulation were significantly reduced by capsaicin pretreatment. The increase in RL and a fall in CDYN induced by ether and capsaicin was significantly reduced or abolished by systemic capsaicin pretreatment, while the histamine-induced bronchoconstriction was only slightly reduced. Ether and capsaicin seemed also to activate capsaicin-sensitive neurons of non-vagal origin since they still caused large effects in animals, which had been locally pretreated with capsaicin on the vagal nerves. The increased RL and decreased CDYN induced by SP was unchanged in capsaicin-pretreated animals. The tracheal tension increase in vitro induced by acetylcholine and histamine was uninfluenced by systemic capsaicin pretreatment. The atropine-sensitive tracheal contraction and atropine-resistant relaxation upon field stimulation seemed also to be unchanged after capsaicin pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Inhibition of cigarette smoke-induced oedema in the nasal mucosa by capsaicin pretreatment and a substance P antagonist.

The effect of cigarette smoke on vascular permeability in the rat nasal mucosa was studied using the Evans blue extravasation method. Exposure to smoke from cigarettes induced a significant extravasation of Evans blue in the nasal mucosa of normal rats, suggesting an increased vascular permeability to plasma proteins. The oedema response was correlated to tar, nicotine and vapour phase components in the smoke. The smoke-induced permeability effect was abolished in rats pretreated neonatally with capsaicin. Also, systemic or local pretreatment with [D-Arg, D-Pro, D-Trp, Leu]Substance P, a substance P antagonist, inhibited the permeability response to cigarette smoke. Insertion of a glass-fibre filter, which removes the particulate phase of the smoke (including nicotine), did not significantly reduce the permeability response. The present findings suggest that the smoke-induced oedema in the rat nasal mucosa is not caused by nicotine but by vapour-phase irritants, which activate capsaicin-sensitive C-fibre afferents. These neurons then release agents such as substance P or a related tachykinin which increase permeability to plasma proteins.

Animals↗

Substance P in sensory nerve fibres contributes to the development of oedema in the rat hind paw after thermal injury.

Immersion of the hind paws of anesthetized rats in hot water for 5 min induced massive plasma protein leakage as indicated by extravasation of Evans blue dye in the skin. The threshold temperature which caused noticeable plasma extravasation was 45 degrees C, a maximal response was obtained between 55 degrees C and 60 degrees C. Pretreatment of rats 2 days after birth with 50 mg kg-1 capsaicin significantly reduced the Evans blue extravasation induced by hot water at 50 degrees C and 60 degrees C, whereas guanethidine pretreatment 24 h before the experiment caused a significantly increased response at 40 degrees C, 45 degrees C and 50 degrees C. When Evans blue was injected between 10 and 120 min after immersion of the paw in hot water, a significant extravasation of the dye was no longer detectable. However, the weight of the paw as well as the weight of the piece of skin taken for Evans blue quantification increased during this period indicating the progressive development of oedema in the skin and underlying tissues. In rats treated with capsaicin as neonates, the increase in paw weight after immersion in water of 50 degrees C for 5 min was significantly delayed during the first hour, but there was no difference after two hours. In rats pretreated with D-Arg1,D-Pro2-,D- Trp7 ,9, Leu11 -substance P, a substance P (SP) antagonist, the Evans blue extravasation was significantly reduced. However, the response, which remained in rats treated with capsaicin as neonates was not blocked by the SP-antagonist. 6 It is concluded that activation of peripheral branches of sensory SP neurones contributes to the initial massive protein extravasation and to the subsequent rate of development of oedema following heat injury. Release of histamine did not significantly contribute to this response at the lower temperatures, although the response was reduced by histamine receptor blocking drugs at 55 degrees and 60 degrees C. Decreasing the sympathetic vasoconstrictor tone by guanethidine resulted in an increased response.

Animals↗

Vascular permeability changes and smooth muscle contraction in relation to capsaicin-sensitive substance P afferents in the guinea-pig.

The occurrence of neurogenic inflammation as indicated by Evans blue extravasation was studied in various organs of the guinea-pig. Electrical stimulation of the trigeminal nerve caused Evans blue extravasation due to increased vascular permeability in the nasal mucosa and gingiva. Vagal stimulation induced extravasation in the epiglottis, larynx, trachea, bronchial tree and esophagus. Splanchnic stimulation induced Evans blue extravasation in the gall bladder, bile ducts and superior mesenteric artery. Stimulation of the inferior mesenteric ganglion caused a marked extravasation in the upper and middle part of both ureters, while pelvic activation induced a reaction in the lower ureter, urinary bladder, urethra and vagina. I.v. substance P (SP) (3 nmol X kg11) or capsaicin (1 mumol X kg-1) both induced extravasation in many tissues including those in which nerve stimulation produced a response. The extravasation responses to SP, capsaicin or nerve stimulation all had similar border-line zones, such as esophagus to stomach, bile ducts to duodenum, rectum to anal mucosa, pulmonary artery to heart and vagina to uterus. Quantitative determinations showed especially large permeability effects in the trachea, umbilical ligament and ureter. The permeability effect of capsaicin and nerve stimulation was abolished in capsaicin-pretreated animals, while the response to SP was still present. Capsaicin pretreatment caused an almost total loss of SP in several visceral organs including the respiratory and urinary tracts. The SP content in these tissues was correlated (r = 0.97) to the Evans blue extravasation following nerve stimulation or i.v. capsaicin. SP and capsaicin caused contractions in vitro of the esophagus, ureter, urinary bladder, trachea and gall bladder. The capsaicin-induced contraction of the trachea was resistant to tetrodotoxin pretreatment. The non-cholinergic, non-adrenergic contraction of the urinary bladder upon field stimulation was still present in capsaicin-pretreated animals. In conclusion, neurogenic inflammation occurs in several organs with a highly region-specific distribution, which is accompanied by the presence of capsaicin-sensitive SP neurons. Both parasympathetic and sympathetic pathways contain capsaicin-sensitive afferent fibres which mediate an increase in vascular permeability most likely by releasing SP. In addition, both capsaicin and SP cause smooth muscle contraction in several visceral organs.

Animals↗

Phenyldiguanide and capsaicin stimulate functionally different populations of afferent C-fibers.

Effects of phenyldiguanide (PDG) and capsaicin (CAP) were compared. (1) The reflex fall in blood pressure following PDG i.v. was only partially but that following CAP i.v. completely inhibited in capsaicin-desensitized rats. (2) Bilateral vagotomy in rats abolished cardiovascular reflexes by PDG i.v., but not those by CAP i.v. (3) Instillation of PDG into the rat trachea did not cause neurogenic plasma extravasation whereas CAP does. (4) Bronchial tone of guinea-pigs remained unchanged after PDG i.v. whereas it was increased by CAP i.v. It is concluded that PDG activates vagal afferent fibers which are distinct from the substance P-containing afferent fibers stimulated by CAP.

Animals↗