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Biomedical subjects

F Lembeck

Publications and source records attributed to F Lembeck.

At least 55 records · Page 3Linked to original sources
PubMed1989

Capsaicin-sensitive afferents and blood pressure regulation during pentobarbital anaesthesia in the rat.

(1) Maintenance of blood pressure was investigated during induction of pentobarbital anaesthesia in rats after elimination of capsaicin-sensitive afferent neurons (capsaicin-denervated rats) as compared to vehicle-treated controls. The catecholamine content of heart and adrenals and the rise in blood pressure following electrical excitation of the spinal adrenergic nerves (pithed rat preparation) was also compared between both groups. (2) Capsaicin-denervated rats and their controls had equal amounts of catecholamines in heart and adrenals as well as equal pressor responses to electrical stimulation of spinal sympathetic nerves, thus excluding an influence of capsaicin on efferent pathways. In the state of consciousness, both groups showed the same blood pressure. (3) In capsaicin-denervated rats and in their controls, pentobarbital-induced anaesthesia (50 mg/kg i.p.) was characterized by a decline in blood pressure during the first 6 min. In the controls, this fall in blood pressure was followed by a slow compensatory rise to a level slightly higher than before anaesthesia, and this level was maintained during the following 60 min. This compensation was completely absent in capsaicin-denervated rats, indicating a role for capsaicin-sensitive nerves in this mechanism. An injection of pentobarbital (50 mg/kg i.p.) in pithed rats reduced the pressor response to electrical stimulation of spinal sympathetic nerves by about 40% in capsaicindenervated rats and in their controls. This inhibitory effect of pentobarbital might be involved in the initial fall in blood pressure in intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1989

Influence of capsaicin-induced denervation on neurogenic and humoral control of arterial pressure.

(1) The influence of capsaicin-sensitive afferent neurones on the regulation of blood pressure by reflex noradrenergic responses and by activation of the renin-angiotensin system was investigated in the rat anaesthetized with pentobarbital. (2) Lowering the pressure in the carotid sinus through unilateral carotid occlusion caused a reflex rise in mean systemic blood pressure which was less marked in capsaicin-pretreated rats than in controls, although an equal drop in mean pressure in the carotid sinus region was observed in both groups. Occlusion of the second carotid artery caused an additional increase in mean systemic blood pressure which was identical in the two groups. (3) Pharmacological blockade of the renin-angiotensin-system with captopril induced a more pronounced hypotonia in capsaicin-pretreated than in control rats. Yet, this difference was based on the impaired noradrenergic counterregulation in capsaicin-pretreated rats, because both groups showed identical responses to captopril following guanethidine-induced adrenergic blockade. (4) Plasma renin activity was increased by a factor of 2 following guanethidine treatment of awake animals. It reached levels 5-7 times higher than those observed in awake animals during pentobarbital anaesthesia. This anaesthesia-induced increase in plasma renin activity was not altered by guanethidine pretreatment. There was no difference in plasma renin activity between controls and capsaicin-pretreated rats under all the conditions tested. (5) These results show that the immediate reflex adjustment of blood pressure is impaired in the capsaicin-pretreated rat, possibly because of an impairment of sensors for low perfusion pressure in the carotid sinus. On the other hand, the renin-angiotension-system remains unimpaired after neonatal capsaicin-pretreatment.

Anesthesia↗
PubMed1989

Effects of endothelin on the cardiovascular system and on smooth muscle preparations in different species.

(1) The actions of porcine endothelin (ET), an endothelium-derived vasoconstrictor peptide, have been investigated in several in vitro smooth and cardiac muscle preparation as well as on the blood pressure of anaesthetized rats and rabbits. (2) In isolated visceral smooth muscles (guinea pig ileum, rat colon and uterus, rabbit jejunum) ET caused a long-lasting contraction which persisted after repeated rinsing. ET did not interfere with the spontaneous phasic activity of the rabbit jejunum or with contractions evoked by histamine or carbachol. (3) ET contracted isolated blood vessels (portal vein of guinea-pig and rat). In isolated perfused organs (rabbit ear, guinea-pig lung, rat mesentery and hindpaw) ET led to a long-lasting vasoconstriction. In the isolated perfused guinea-pig lung ET caused vaso- and bronchoconstriction. (4) ET produced a long-lasting positive inotropic effect in spontaneously beating isolated guinea-pig atria. The positive inotropic action of strophanthin was augmented in the presence of ET. (5) In the isolated perfused guinea-pig and rat hearts the prominent effect of ET was a long-lasting coronary vasoconstriction. (6) Pithed rats responded to i.v. injection of ET with a long-lasting increase in blood pressure. In pentobarbitone anaesthetized rats pretreated either with atropine, with guanethidine plus atropine, or with guanethidine plus atropine plus indomethacin, the long-lasting increase in blood pressure was smaller than in pithed rats whereas the initial short-lasting decrease in blood pressure was more pronounced; in pentobarbitone anaesthetized rabbits endothelin caused bronchoconstriction, a decrease in blood pressure and a pronounced increase in central venous pressure possibly resulting from pulmonary or coronary artery constriction or a combination of both effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Capsaicin-induced stimulation of polymodal nociceptors is antagonized by ruthenium red independently of extracellular calcium.

The dual effect of capsaicin on primary afferent neurons, excitation and stimulation of transmitter release, its dependence on extracellular calcium and its modulation by Ruthenium Red have been investigated in the rabbit ear. Injection of capsaicin into the central artery of the isolated perfused ear with intact neuronal connection induced a reflex fall in systemic arterial blood pressure of the anaesthetized rabbit. Addition of Ruthenium Red (0.6-20 microM) to the perfusate of the ear reversibly attenuated this response in a dose-dependent manner. Perfusion of the ear with a Ca2+-free, 3 mM EGTA-containing physiological salt solution enhanced the capsaicin-evoked depressor reflex but did not prevent the inhibitory action of Ruthenium Red. Perfusion of the isolated rabbit ear with capsaicin (10 microM)-containing physiological salt solution induced the release of substance P-like immunoreactivity which was inhibited by Ruthenium Red (0.6-20 microM) and by omission of extracellular Ca2+. The results demonstrate that capsaicin-evoked transmitter release is dependent on extracellular calcium while capsaicin-evoked excitation is not reduced in a Ca2+-free perfusate. Both effects of capsaicin are potently inhibited by Ruthenium Red. The fact that capsaicin-induced excitation of primary afferents is antagonized by Ruthenium Red also in the absence of extracellular Ca2+ suggests this inhibitory action of Ruthenium Red is not only mediated by inhibition of transmembrane Ca2+ fluxes.

Animals↗
PubMed1989

Evidence for an involvement of substance P, but not cholecystokinin-like peptides, in hexamethonium-resistant intestinal peristalsis.

It has previously been found that, in the presence of naloxone, the ganglionic blocking drug hexamethonium fails to completely block peristaltic motility in the isolated ileum of the guinea-pig. This hexamethonium-resistant peristaltic activity is coordinated by enteric nerves since it is abolished by tetrodotoxin. In the present study the neurotransmitter circuitry of this type of peristalsis was studied by means of specific antagonists. Atropine totally suppressed hexamethonium-resistant peristalsis. This type of peristalsis was also strongly inhibited by the tachykinin antagonist, spantide, if a concentration sufficient to antagonize neuronally located substance P receptors was employed. In contrast, the cholecystokinin antagonist, lorglumide, caused only a slight inhibition of hexamethonium-resistant peristalsis. Both substance P and the cholecystokinin-related peptide, ceruletide, potently stimulated the hexamethonium-resistant type of peristaltic activity. These data indicate that, after blockade of nicotinic acetylcholine receptors, tachykinins mediate neuroneuronal coordination of peristalsis whereas acetylcholine acting via muscarinic receptors may be primarily responsible for neuromuscular transmission. Cholecystokinin-like peptides appear to play a modulator rather than a mediator role in hexamethonium-resistant peristalsis.

Animals↗
PubMed1989

Effects of the bradykinin antagonist B4310 on smooth muscles and blood pressure in the rat, and its enzymatic degradation.

1. Six competitive bradykinin (Bk) antagonists were tested for their agonistic properties on the rat uterus. Five of these peptides showed agonistic effects only at concentrations at least two orders of magnitude higher than those of bradykinin. 2. The antagonistic potency of Lys-Lys-3-Hyp-5,8-Thi-7-DPhe-Bk (B4310) in the rat uterus (pA2 = 7.24) and in the rat duodenum (pA2 = 7.31) was very similar to that determined in an earlier study for the antagonism of the bradykinin-induced stimulation of the trigeminal nerve in the rabbit iris sphincter muscle preparation (pA2 = 7.59). 3. The fall in mean arterial blood pressure induced by i.a. injections of bradykinin was greatly reduced during an i.a. infusion of B4310, but not 10 min thereafter, which indicates a rapid inactivation of B4310 in vivo. Bacitracin possibly interferes with the enzymatic cleavage of B4310 but seems to have no effect on the degradation of bradykinin. 4. An i.a. infusion of captopril greatly enhanced the potency of bradykinin in inducing a fall in arterial blood pressure, confirming the important role of angiotensin converting enzyme in the cleavage of bradykinin. However, the design of this experiment did not allow conclusions about the effect of captopril on the degradation of B4310. 5. B4310 incubated with rat lung tissue disappeared from the incubation medium within a few minutes, i.e. as fast as bradykinin, which explains its short duration of action in vivo. Captopril partially inhibited the cleavage of both bradykinin and B4310. 6. The present results show that the bradykinin antagonists available at present are useful tools for the investigation of the biological role of bradykinin. However, the susceptibility to enzymatic degradation may limit their usefulness in animal experiments or in clinical studies.

Animals↗
PubMed1989

Galanin and vasopressin coexist in the rat hypothalamo-neurohypophyseal system.

Using indirect immunofluorescence methods and antisera raised against galanin (GAL) and vasopressin (VP), we have demonstrated both peptides coexisting in the very same cell bodies in the supraoptic and magnocellular paraventricular nuclei and the magnocellular accessory cells of the lateral hypothalamic area. Furthermore, dehydration and salt loading, which is known to cause release and depletion of VP and oxytocin from the neurohypophysis, also caused a marked reduction of GAL-like immunoreactivity in the posterior lobe of the pituitary but had no effect on hypothalamic GAL immunoreactivity. Systemically administered GAL caused a brief small increase in blood pressure with no effect on heart rate. A thousandfold molar concentration of GAL, compared of VP, was required to induce comparable effects on blood pressure. GAL itself had no modulatory effect on VP-induced pressor response. Systemically administered GAL resulted in mild diuresis whereas VP caused complete and sustained inhibition of diuresis. GAL had no effect on VP-induced anti-diuresis effects. The significance of the coexistence and corelease of GAL and VP remains to be elucidated.

Animals↗
PubMed1988

Species-related differences in the capsaicin-sensitive innervation of the rat and guinea-pig ureter.

1. Comparison of the tissue content of calcitonin gene-related peptide (CGRP)-immunoreactivity (IR) and tachykinin (TK)-IR in the rat and guinea-pig ureter showed that in the rat tissue levels of CGRP-IR were 33-fold higher than those of TK-IR. In the guinea-pig ureter, both peptides were present in nearly the same concentration. 2. The in-vitro release of neuropeptides from guinea-pig and rat ureters was investigated using capsaicin as a stimulus for afferent neurons. Capsaicin induced the simultaneous release of CGRP-IR and TK-IR from the guinea-pig ureter while in the rat only the release of CGRP-IR was detectable. 3. It is known that TK potently stimulate and CGRP inhibits ureteric smooth muscle contractions. When the effect of capsaicin on ureteric motility was investigated in guinea-pig and rat, only in the guinea-pig ureter a stimulatory action ascribable to capsaicin-induced TK release was observed thus supplementing the results obtained by radioimmunoassay. 4. The results show that considerable species differences exist concerning the ratio of CGRP and TK which is stored and released from ureteric afferent nerve terminals. As a consequence, different functional responses are obtained in both species upon stimulation of these neurons by capsaicin. In the rat ureter, the capsaicin-sensitive innervation seems to be only inhibitory while in the guinea-pig stimulatory and inhibitory transmitters are released. The physiological significance of the simultaneous release of transmitters with opposing effects needs further investigation.

Animals↗
PubMed1988

Quantitative assay of capsaicin-sensitive thiamine monophosphatase and beta-glycerophosphatase activity in rodent spinal cord.

The axon terminals of some capsaicin-sensitive sensory neurons in the spinal cord of the rat contain high amounts of acid phosphatase (EC 3.1.3.1) activity. We quantitated this activity in control and capsaicin-treated rats and mice in a biochemical assay using beta-glycerophosphate (beta-GP) and thiamine monophosphate (TMP), which have both been used in previous histological investigations, as substrates and measured the amount of phosphate liberated from particular fractions. The ventral spinal cord of rats yielded 209 +/- 9 (mean +/- S.E.M.) nmol phosphate/mg protein/h from beta-GP and 18 +/- 5 nmol from TMP; the values for the upper dorsal horn are 544 +/- 42 and 198 +/- 12 for beta-GP and TMP respectively. Values for mouse spinal cord tissue are quite similar; the spinal cord of guinea pigs contains lower amounts of beta-GPase and very little TMPase activity per mg protein. There was a fairly broad pH optimum between 5.4 and 6.3. After capsaicin (50 mg/kg s.c.) pretreatment, beta-GPase activity in the upper dorsal horn was decreased by 29% in rats and by 17% in mice; TMPase activity was reduced by 48% and 37% respectively. Values in the ventral spinal cord were unchanged. It is proposed that biochemical measurement of TMPase activity might be useful in quantitative investigations of acid phosphatase activity (e.g. "FRAP") in capsaicin-sensitive sensory neurons.

Animals↗
PubMed1988

Neonatal capsaicin treatment of rats reduces ACTH secretion in response to peripheral neuronal stimuli but not to centrally acting stressors.

1. Plasma adrenocorticotrophic hormone (ACTH) concentrations were measured in rats following exposure to anaesthetic agents, after stimulation of peripheral sensory nerves, and during psychological stress. 2. In rats, kept in their home cages, the i.p. injection of sodium pentobarbitone did not cause an increase in plasma ACTH, whereas injection of urethane increased plasma ACTH several times. In rats transferred to a glass dessicator and inhaling oxygen, plasma ACTH was more than 3 fold higher than in rats in their home cage. Exposure to nitrous oxide, halothane or ether in a glass dessicator produced significantly higher plasma ACTH concentrations when compared to exposure in the home cage. 3. In rats anaesthetized with pentobarbitone, the electrical stimulation of large myelinated afferents in the sciatic nerve did not trigger a measurable increase in ACTH secretion, whereas stimulation of afferent A delta- and C-fibres significantly elevated plasma ACTH concentrations. Rats treated as neonates with capsaicin showed an attenuated ACTH response to A and C-fibre stimulation. 4. Similarly, capsaicin pretreatment reduced the increase in ACTH secretion during morphine withdrawal; a similar effect was produced by clonidine. 5. ACTH secretion following open field exposure, ether stress or hypoglycaemia was not changed by capsaicin pretreatment. 6. It was concluded that capsaicin-sensitive afferents are involved in the secretion of ACTH elicited by somatosensory forms of stress. Centrally evoked ACTH release is not affected by capsaicin pretreatment.

Adrenocorticotropic Hormone↗
PubMed1988

Effects of clonidine and yohimbine on a C-fibre-evoked blood pressure reflex in the rat.

1. The involvement of alpha 2-adrenoceptors in a capsaicin-induced depressor reflex in the rat has been investigated. 2. The reflex fall in blood pressure following an intra-arterial injection of capsaicin was partially blocked by an intrathecal infusion of clonidine (1 microgram) at the spinal cord level L4-L5, an effect which was abolished by the prior intrathecal infusion of yohimbine (5 micrograms). 3. Clonidine (1 microgram) given intracisternally blocked the depressor reflex almost completely; however, it also produced a gradual, prolonged fall in mean carotid pressure. 4. Yohimbine (20 micrograms) given intracisternally did not change mean blood pressure but had a dual effect on the depressor reflex in response to the capsaicin injection: a short period of enhanced reflex response was followed by a long lasting inhibition of the response. 5. It was concluded that alpha 2-adrenoceptors in the spinal cord inhibit the capsaicin-evoked depressor reflex and that pre- and postsynaptic alpha 2-adrenoceptors in the brain stem modulate this reflex.

Animals↗
PubMed1987

Calcitonin gene-related peptide is a potent relaxant of intestinal muscle.

The motor effects of calcitonin gene-related peptide (CGRP) on the guinea-pig ileum (GPI) longitudinal muscle were investigated. CGRP (0.1-100 nM) concentration dependently relaxed ilea precontracted with histamine and inhibited electrically induced cholinergic contractions. At higher concentrations (3-100 nM) CGRP also caused a slight contraction of non-stimulated ilea. Further pharmacological analysis of the CGRP-induced relaxation which seems to be the primary CGRP effect in the GPI, indicated that the effect was due to a direct action on the longitudinal muscle.

Animals↗
PubMed1987

Peripheral effects of opioid drugs on capsaicin-sensitive neurones of the guinea-pig bronchus and rabbit ear.

The effect of a potent opioid agonist, [D-Met2, Pro5]-enkephalinamide was investigated on two responses involving capsaicin-sensitive afferent neurones, namely, atropine-resistant contractions of the guinea-pig bronchus evoked by electrical field stimulation and the nociceptor stimulation to intraarterial injections of acetylcholine or capsaicin into the vascularly isolated rabbit ear. The hypotheses to be tested were whether (a) opioid receptor activation may inhibit mediator release from primary afferent neurones and (b) the opioid could exert an analgesic effect at a peripheral site of action. Non-cholinergic contractions of the guinea-pig isolated main bronchi due to electrical stimulation were concentration-dependently inhibited by [D-Met2, Pro5]-enkephalinamide (10 nM-1 microM). This effect was abolished by naloxone (1 microM). Naloxone alone induced no change in the stimulation-evoked contractions of the bronchus, indicating that no endogenous opioid control was present. Substance P and neurokinin A induced bronchial contractions that were not influenced by [D-Met2, Pro5]-enkephalinamide. This indicates that [D-Met2, Pro5]-enkephalinamide inhibits electrically-evoked bronchial contractions by reduced mediator release from capsaicin-sensitive sensory nerve endings, since these contractions are most probably brought about by tachykinins, released from afferent neurones. Capsaicin-induced bronchial contractions were in contrast to electrical stimulation not influenced by [D-Met2, Pro5]-enkephalinamide which suggests a different site of action. The activation of sensory neurones in the rabbit ear by i.a. injection of acetylcholine and capsaicin was not reduced under infusion of [D-Met2, Pro5]-enkephalinamide (1 and 10 microM) or lofentanil (1 and 10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1987

Is ganglionic transmission through nicotinic receptors essential for the peristaltic reflex in the guinea-pig ileum?

Peristaltic reflex activity in the guinea-pig isolated ileum was elicited by slow intraluminal infusion of Tyrode solution. The reflex was abolished by the ganglionic blocking drug hexamethonium. However, in more than half of the preparations, the peristaltic reflex was restored by the opioid antagonist naloxone. Hexamethonium-resistant peristaltic waves were blocked by tetrodotoxin or atropine. These data suggest that ganglionic transmission through nicotinic acetylcholine receptors may not be essential for the peristaltic reflex provided that the inhibitory action of endogenous opioids has been eliminated.

Animals↗
PubMed1987

Stress induced ACTH release in capsaicin treated rats.

The plasma concentrations of adrenocorticotropic hormone (ACTH) in rats pretreated with capsaicin as neonates were compared with those of control rats pretreated with the capsaicin vehicle. Capsaicin pretreatment has been shown earlier to abolish the increase in plasma ACTH concentration induced by cold stress while not affecting that induced by restraint stress. In the present experiments rats pretreated with capsaicin showed the same increase in plasma ACTH concentration in response to an i.v. infusion of ovine-corticotropin releasing factor as control rats pretreated with the capsaicin vehicle. Intraperitoneal injection of formalin, surgical stress and intravenous infusion of (-)-isoprenaline increased plasma ACTH concentrations in control rats. In capsaicin pretreated rats the increase in plasma ACTH was significantly attenuated. It is concluded that capsaicin-sensitive sensory neurones mediate the activation of pituitary ACTH secretion in response to somatosensory stimuli. The function of the corticotroph cells of the anterior pituitary is not impaired by capsaicin treatment.

Adrenocorticotropic Hormone↗
PubMed1987

Evaluation of a new and potent cholecystokinin antagonist on motor responses of the guinea-pig intestine.

The potency and selectivity of D,L-4-(3,4-dichloro-benzoyl-amino)-5-(dipentyl-amino)-5-oxo-pen tan oic acid (CR 1409) as a cholecystokinin (CCK) antagonist was investigated on motor responses of the longitudinal and circular muscles of the guinea-pig isolated ileum. CR 1409 was further used to examine whether nerve-mediated motor responses to electrical field stimulation or distension of the gut wall may involve the release of CCK-like peptides. CR 1409 (0.06-2.1 microM) antagonized longitudinal muscle responses to ceruletide (caerulein, a CCK-related decapeptide) in a concentration dependent and competitive manner (pA2 7.77); responses to CCK-octapeptide (CCK-8) were antagonized with a similar potency. Contractions of the circular muscle evoked by ceruletide were also blocked by CR 1409 (0.2-0.4 microM). Longitudinal muscle contractions in response to dimethylphenylpiperazinium, bethanechol, histamine, substance P, or 5-hydroxytryptamine (5-HT), and circular muscle contractions evoked by acetylcholine, 5-HT, substance P, or substance K were not altered by CR 1409 (0.4 microM). Longitudinal muscle contractions induced by electrical field stimulation (with pulses delivered at 0.05 and 1 Hz in the absence, and at 5 Hz in the presence of atropine) were not or only slightly reduced by CR 1409 (0.4 microM). Longitudinal contractions due to activation of extrinsic nerves by capsaicin remained unaltered in the presence of CR 1409 (0.4 microM). Reflex contractions of the circular muscle, induced by balloon distension and recorded orally to the site of distension, and peristaltic activity elicited by intraluminal infusion of Tyrode solution remained unaffected by CR 1409 (0.4 microM). 5 These findings indicate that CR 1409 is a potent and selective antagonist of CCK-like peptides in the guinea-pig ileum. The results do not provide any evidence that CCK-like peptides, released from extrinsic or intrinsic neurones, are involved in nerve-mediated contractions of intestinal muscle and in the peristaltic reflex.

Animals↗
PubMed1987

Effect of bradykinin antagonists on bradykinin-induced plasma extravasation, venoconstriction, prostaglandin E2 release, nociceptor stimulation and contraction of the iris sphincter muscle in the rabbit.

1 The inhibition of the bradykinin-induced plasma extravasation by six bradykinin (Bk) antagonists was tested on rabbit skin. All of them showed inhibitory effects without an agonistic action in the does used. B4310 (Lys-Lys-3-Hyp-5,8-Thi-7-DPhe-Bk) was the most active antagonist and was therefore used in the subsequent experiments. 2 B4310 (5-500 nM) antagonized the bradykinin-induced reduction of the venous outflow from the rabbit isolated ear in dose-dependent manner without affecting the arterial vasoconstriction induced by angiotensin II. 3 The bradykinin-induced release of prostaglandin E2 (PGE2) from the perfused rabbit ear was reduced by 63% when B4310 (800 nM) was infused before, during and after the bradykinin injection. 4 Bradykinin was injected into the ear artery of anaesthetized rabbits and the reflex hypotensive response was used as indicator of the nociception. The response was antagonized by a local infusion of B4310 (50 and 500 nM). The antagonism was dose-dependent and reversible. The parallel shift of the dose-response curve to bradykinin suggests a competitive inhibition. However, B4310 did not antagonize acetylcholine-induced nociceptor stimulation. 5 B4310 inhibited bradykinin-induced stimulation of the trigeminal nerve which results in a substance P-mediated contraction of the iris sphincter muscle. A pA2 of 7.59 was calculated. B4310 did not inhibit capsaicin-induced contractions. 6 It is concluded that B4310 inhibits specifically five different actions of bradykinin which are related to its possible pathophysiological role.

Acetylcholine↗