PubMed Health⌕ Search

Biomedical subjects

W W Blessing

Publications and source records attributed to W W Blessing.

At least 19 recordsLinked to original sources
PubMed2006

Activation of dopamine D2 receptors in the CNS inhibits sympathetic cutaneous vasomotor alerting responses (SCVARs), contributing to clozapine's SCVAR-inhibiting action.

Sympathetic neural outflow to thermoregulatory cutaneous vascular beds is selectively activated when the individual is aroused, so that cutaneous blood flow is characterized by sudden alerting-related falls to near zero levels ("SCVARs", sympathetic cutaneous vasomotor alerting responses). Our previous work shows that clozapine, an atypical antipsychotic drug used in schizophrenia, profoundly inhibits SCVARs. Clozapine, conventionally assumed to have a dopamine D(2) receptor antagonist action, also increases baseline cutaneous blood flow and lowers body temperature. However dopamine D(2) receptor agonists lower temperature, suggesting that a dopamine D(2)agonist action might also reduce SCVARs. The present study determined whether a dopamine D(2)agonist action contributes to clozapine's SCVAR-inhibiting effect. SCVARs were measured in conscious rats with a Doppler ultrasonic flow probe chronically implanted around the base of the artery, with probe wires passing subcutaneously to a headpiece. Doppler signals were monitored via a flexible connection between the headpiece and a swivel device in the roof of the cage. Apomorphine (0.1-0.5 mg/kg), quinpirole (0.05-0.25 mg/kg) and 7-OH-DPAT (0.02-0.5 mg/kg) dose-dependently reduced SCVARs. Pre-treatment with the dopamine receptor antagonist spiperone (20 microg/kg) but not the D(1) antagonist SCH-23390 or the peripheral dopamine D(2) antagonist domperidone, abolished this effect. Spiperone pre-treatment reduced the SCVAR-inhibiting action of clozapine (0.06-1.0 mg/kg). Chlorpromazine (0.1-10 mg/kg) also dose-dependently inhibited SCVARs, but this effect was not reduced by pre-treatment with spiperone. Mechanisms underlying clozapine's SCVAR-inhibiting effect include dopamine D(2) receptor agonism, not dopamine D(2) receptor antagonism, calling into question the mechanism of the drug's therapeutic action in schizophrenia.

Animals↗
PubMed2006

Clozapine reverses increased brown adipose tissue thermogenesis induced by 3,4-methylenedioxymethamphetamine and by cold exposure in conscious rats.

Clozapine, an atypical antipsychotic agent important for the treatment of schizophrenia, has marked inhibitory effects on sympathetic outflow to the thermoregulatory cutaneous circulation. In rabbits clozapine reverses ear pinna vasoconstriction induced either by administration of MDMA (3,4-methylenedioxymethamphetamine, ecstasy) or by exposing the animal to a cold environment. In rats, both these procedures are known to increase sympathetic activation of interscapular brown adipose tissue (iBAT) thermogenesis, important for heat production in the rat. In the present study in conscious rats we determined whether clozapine reduces iBAT thermogenesis induced by MDMA and by exposure to cold. We designed our study so that we could also determine effects of clozapine on the acute (stress-induced) increases in iBAT thermogenesis initiated by the process of s.c. injection. MDMA increased iBAT temperature (+1.7+/-0.2 degrees C after 90 min, P<0.01, n=14 measurements from seven rats each studied on two occasions). Clozapine acutely reversed the MDMA-elicited increase in iBAT temperature (-1.3+/-0.2 degrees C 60 min after clozapine treatment following MDMA versus +0.3+/-0.2 degrees C for 60 min after vehicle treatment following MDMA, P<0.01, n=7). Clozapine also reduced stress-induced increases in iBAT temperature, as well as increases elicited by exposing rats to a cold (5 degrees C) environment. Results, taken together with our previous findings, suggest that MDMA activates the sympathetic thermoregulatory outputs (including the output to iBAT) that defend body temperature against cold exposure and that increase body temperature in response to environmental stress. Clozapine's marked inhibition of iBAT thermogenesis may provide a clue to its marked tendency to cause obesity when used to treat humans with mental disorders including schizophrenia. Our demonstration in rats that clozapine decreases sympathetically-mediated increases in iBAT temperature elicited by MDMA adds to the likelihood that clozapine and clozapine-like agents might be therapeutically effective in life threatening hyperthermia induced by MDMA in humans.

3,4-Methylenedioxyamphetamine↗
PubMed2004

CRF1 receptor antagonist CP-154,526 reduces cardiovascular responses during acute psychological stress in rabbits.

We examined the effect of CP-154,526 on cardiovascular changes elicited in conscious rabbits by stressful stimuli (loud sound, cage move, pinprick, formaldehyde vapour and air-jet stress). CP-154,526 substantially reduced pressor and heart rate responses to these stimuli (both vagally and sympathetically mediated), and reduced QT shortening during air-jet stress. Blocking of central CRF1 receptors attenuates cardiovascular responses to environmental stimuli, presumably by affecting brain centres that control cardiovascular functions.

Adrenergic beta-Antagonists↗
PubMed2004

5-hydroxytryptamine 1A receptor activation reduces cutaneous vasoconstriction and fever associated with the acute inflammatory response in rabbits.

5-Hydroxytryptamine(1A) (5-HT1A) receptor activation reduces body temperature partially by dilating the thermoregulatory cutaneous vascular bed, thereby increasing heat transfer to the environment. Constriction of this vascular bed, with consequent reduction of heat transfer to the environment, contributes to fever associated with the acute inflammatory response. Thus activation of 5-HT1A receptors might inhibit thermoregulatory cutaneous vasoconstriction and reduce the fever associated with the acute inflammatory response. The present study tested this hypothesis in conscious unrestrained rabbits. The acute inflammatory reaction was induced with i.v. lipopolysaccharide (LPS, 0.5 microg/kg). Body temperature was measured with an i.p. telemetric probe, and ear pinna blood flow was measured with a chronically implanted Doppler ultrasonic probe. 5-HT1A receptors were activated with i.v. 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). LPS increased body temperature by +1.7+/-0.2 degrees C during the first hour after administration. The ear pinna Doppler blood flow signal fell from 69+/-11 to 5+/-1 cm/s within 15 min (n=7, P<0.01) and remained at a low level for approximately 1 h after LPS. When administered 45 min after LPS, 8-OH-DPAT (0.1 mg/kg i.v.) reversed this fall, increasing the Doppler signal from 6+/-1 to 55+/-7 cm/s (P<0.01, n=6), and reduced the rise in body temperature. Treatment with 8-OH-DPAT (0.1 mg/kg i.v.) 5 min before and 30 min after LPS entirely prevented the LPS-induced fall in ear pinna blood flow, and reduced the rise in body temperature from 1.7+/-0.2 degrees C to 0.7+/-0.2 (n=7, P<0.01). Treatment with WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride) (0.1 mg/kg i.v.) prevented and reversed the effects of 8-OH-DPAT. Thus activation of 5-HT1A receptors reduces thermoregulatory cutaneous vasoconstriction and fever occurring as part of the acute inflammatory response. Our findings elucidate the neurotransmitter mechanisms underlying expression of an important component of the febrile response, and suggest that drugs with 5-HT1A agonist properties might be therapeutically useful when it is clinically important to reduce this response.

Animals↗
PubMed2003

5-Hydroxytryptamine 1A receptors inhibit cold-induced sympathetically mediated cutaneous vasoconstriction in rabbits.

5-HT1A receptor agonists lower body temperature. We have investigated whether activation of 5-HT1A receptors inhibits cutaneous sympathetic discharge so that dilatation of the cutaneous vascular bed lowers body temperature by increasing heat transfer to the environment. We measured ear pinna blood flow in conscious rabbits (with chronically implanted Doppler ultrasound flow probes), and postganglionic sympathetic vasomotor nerve activity in anaesthetized rabbits. Recordings from conscious rabbits were made in a cage at 26 degrees C and the rabbit was then transferred to a cage at 10 degrees C. The ear pinna Doppler signal fell from 56 +/- 4 cm s-1 in the 26 degrees C cage to 4 +/- 1 cm s-1 (P < 0.0001, n = 24) after 30 min in the 10 degrees C cage, and body temperature increased from 38.8 +/- 0.2 to 39.0 +/- 0.2 degrees C (P < 0.01, n = 24). The 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.1 mg kg-1 I.V.) reversed the cold-induced fall in ear pinna blood flow (Doppler signal increased from 5 +/- 1 to 55 +/- 8 cm s-1, P < 0.001, n = 7) within 5 min when administered 30 min after transfer to the 10 degrees C cage, and prevented the fall in ear pinna blood flow when administered before the rabbit was transferred to the 10 degrees C cage. Body temperature decreased after administration of 8-OH-DPAT. These changes were abolished by the specific 5-HT1A antagonist WAY-100635 (0.1 mg kg-1 I.V.). In anaesthetized rabbits, 8-OH-DPAT (0.1 mg kg-1 I.V.) reduced resting postganglionic cutaneous sympathetic vasomotor discharge, and prevented the increase normally elicited by cooling the trunk. Our experiments constitute the first demonstration that activation of 5-HT1A receptors powerfully inhibits cold-induced increases in cutaneous sympathetic vasomotor discharge, thereby dilating the cutaneous vascular bed and increasing transfer of heat to the environment.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2003

Clozapine reverses hyperthermia and sympathetically mediated cutaneous vasoconstriction induced by 3,4-methylenedioxymethamphetamine (ecstasy) in rabbits and rats.

Life-threatening hyperthermia occurs in some individuals taking 3,4-methylenedioxymethamphetamine (MDMA, ecstasy). In rabbits, sympathetically mediated vasoconstriction in heat-exchanging cutaneous beds (ear pinnae) contributes to MDMA-elicited hyperthermia. We investigated whether MDMA-elicited cutaneous vasoconstriction and hyperthermia are reversed by clozapine and olanzapine, atypical antipsychotic agents. Ear pinna blood flow and body temperature were measured in conscious rabbits; MDMA (6 mg/kg, i.v.) was administered; and clozapine (0.1-5 mg/kg, i.v.) or olanzapine (0.5 mg/kg, i.v.) was administered 15 min later. One hour after MDMA, temperature was 38.7 +/- 0.5 degrees C in 5 mg/kg clozapine-treated rabbits and 39.0 +/- 0.2 degrees C in olanzapine-treated rabbits, less than untreated animals (41.5 +/- 0.3 degrees C) and unchanged from pre-MDMA values. Ear pinna blood flow increased from the MDMA-induced near zero level within 5 min of clozapine or olanzapine administration. Clozapine-induced temperature and flow responses were dose-dependent. In urethane-anesthetized rabbits, MDMA (6 mg/kg, i.v.) increased ear pinna postganglionic sympathetic nerve discharge to 217 +/- 33% of the pre-MDMA baseline. Five minutes after clozapine (1 mg/kg, i.v.) discharge was reduced to 10 +/- 4% of the MDMA-elicited level. In conscious rats made hyperthermic by MDMA (10 mg/kg, s.c.), body temperature 1 hr after clozapine (3 mg/kg, s.c.) was 36.9 +/- 0.5 degrees C, <38.6 +/- 0.3 degrees C (Ringer's solution-treated) and not different from the pre-MDMA level. One hour after clozapine, rat tail blood flow was 24 +/- 3 cm/sec, greater than both flow in Ringer's solution-treated rats (8 +/- 1 cm/sec) and the pre-MDMA level (17 +/- 1 cm/sec). Clozapine and olanzapine, by interactions with 5-HT receptors or by other mechanisms, could reverse potentially fatal hyperthermia and cutaneous vasoconstriction occurring in some humans after ingestion of MDMA.

Anesthesia↗
PubMed2003

Electrocardiographic changes associated with the nasopharyngeal reflex in conscious rabbits: vago-sympathetic co-activation.

Electrocardiographic responses were assessed in conscious rabbits when the nasopharyngeal reflex was elicited by inhalation of formaldehyde vapour. There was a profound fall in heart rate (224+/-5 to 64+/-4 beats per min (bpm)) associated with abnormal or absent P-waves. There were no changes in the QRS complex. The R-T interval (control value 118+/-4 ms) was initially shortened to 107+/-3 ms and then prolonged to 130+/-4 ms. Heart rate and P-wave changes were prevented by muscarinic cholinergic blockade with methylscopolamine. The R-T shortening was reduced by 79+/-4% by beta-adrenergic blockade with propranolol. Methylscopolamine also unmasked small tachycardic responses (5-25 bpm) in 5/7 animals. This tachycardia was prevented by propranolol. Thus both parasympathetic vagal cardiac nerves and sympathetic cardiac nerves are activated during the nasopharyngeal reflex, with increased vagal effects in the sino-atrial node, and increased sympathetic effects in the ventricular myocardium.

Animals↗
PubMed2003

5-hydroxytryptamine(2A) receptors regulate sympathetic nerves constricting the cutaneous vascular bed in rabbits and rats.

Hyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA) is partially due to sympathetically-mediated cutaneous vasoconstriction that impairs normal heat dissipation. MDMA acts by releasing monoamines, including 5-hydroxytryptamine (5-HT), but receptor mechanisms underlying MDMA-elicited hyperthermia and cutaneous vasoconstriction are not known. The specific 5-HT2A agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) is a potent hallucinogen that also causes marked hyperthermia, suggesting the possibility that DOI, via stimulation of 5-HT2A receptors, might also cause sympathetically mediated cutaneous vasoconstriction. We tested this hypothesis in conscious unrestrained rabbits and rats. Blood flow was assessed by chronically implanted Doppler ultrasonic flow probes. Body temperature was measured by i.p. telemetric probes. We compared effects of DOI on cutaneous blood flow (ear pinna in rabbits, tail in rats) with effects on mesenteric blood flow and arterial pressure.Hyperthermia induced by DOI (5-100 microgram/kg i.v. in rabbits and 100 microgram/kg s.c. in rats) was preceded and accompanied by markedly reduced blood flow to the cutaneous bed, with no change in flow to the mesenteric bed. In rabbits, DOI (5 microgram/kg i.v.) did not affect arterial pressure or heart rate. DOI (100 microgram/kg i.v.) caused a moderate rise in arterial pressure. In rabbits, the 5-HT2A receptor antagonists ketanserin (0.3 mg/kg i.v.) and AC90179 (0.5 mg/kg i.v.) reversed the ear pinna vasoconstriction induced by DOI (5 microgram/kg i.v.). In rats, ketanserin (3 mg/kg s.c.) reversed tail vasoconstriction and hyperthermia induced by DOI (100 microgram/kg s.c.). In rabbits, the cutaneous vasoconstricting effect of DOI (5 microgram/kg i.v.) was substantially abolished in the ipsilateral ear pinna after interruption of preganglionic sympathetic nerve activity by unilateral section of the cervical sympathetic trunk. Thus hyperthermia evoked by direct stimulation of 5-HT2A receptors is associated with marked sympathetically mediated vasoconstriction, selective for the cutaneous bed. Impairment of the ability to dissipate heat following drug-induced stimulation of 5-HT2A receptors is likely to contribute to hyperthermia induced by MDMA and by hallucinogenic drugs such as LSD.

Animals↗
PubMed2003

CRF1-receptor antagonist CP-154526 reduces alerting-related cutaneous vasoconstriction in conscious rabbits.

Cutaneous vasoconstrictor responses elicited by salient stimuli in conscious rabbits may be a sensitive physiological index of emotional arousal/anxiety. Ear-pinna blood flow was measured by preimplanted laser Doppler probes, and animals were exposed to situations involving different types of potentially salient stimuli before and after i.v. administration of CP-154526 (15 mg/kg) or diazepam (4 mg/kg). At rest, ear-pinna blood flow was stable (coefficient of varition=11+/-2) and remained at high level 93+/-13% of test time. Exposure to novel environment elicited flow fluctuations (coefficient of variation=79+/-8) and reduced amount of time spent at high level to 25+/-6%. Defined unconditioned stimuli caused rapid falls in ear-pinna flow, with nociceptive stimulation producing more vigorous and consistent effects (flow response index 0.66+/-0.02) compared with non-nociceptive (flow response index 0.49+/-0.04). CP-154526 slightly raised mean arterial pressure (from 81+/-2 to 93+/-3 mmHg), increased heart rate (from 198+/-1 to 220+/-4 beats/min) and produced a mild vasoconstriction in the ear-pinna bed (flow fell from 46+/-10 to 25+/-6 cm/s). CP-154526 substantially reduced cutaneous vasoconstrictor responses elicited by the exposure to novel environment and by defined non-nociceptive stimuli, with flow-response index fall from 0.53+/-0.10 to 0.17+/-0.09 and from 0.47+/-0.04 to 0.24+/-0.04, respectively, without affecting responses to nociceptive stimuli. Diazepam reduced only vasoconstrictor responses elicited by the exposure to novel environment, with flow-response index fall from 0.40+/-0.12 to 0.27+/-0.07. Sensitivity of rapid changes in rabbit ear-pinna blood flow to anxiolytic drugs supports the idea that increased cutaneous vascular tone reflects enhanced arousal in rabbits.

Animals↗
PubMed2003

Lower brainstem pathways regulating sympathetically mediated changes in cutaneous blood flow.

1. When the individual is alerted by painful or salient stimuli, there is a vigorous sympathetically mediated constriction of the cutaneous vascular bed. We investigated central pathways mediating this response using chronically implanted Doppler ultrasonic probes to measure cutaneous blood flow in the rabbit ear pinna and in the rat tail. 2. Blockade of neuronal function in the amygdala prevents cutaneous vasoconstriction elicited by salient stimuli, but does not prevent the response to painful stimuli. Blockade of neuronal function in raphe magnus/pallidus and the parapyramidal region in anesthetized rabbits prevents cutaneous vasoconstriction elicited by painful stimuli. A similar region of the medullary raphe regulates tail artery vasoconstriction in rats. Inhibition of neuronal function in this region reverses cutaneous vasoconstriction induced by cooling the animal. 3. Bulbospinal presympathetic neurons in the rostral medullary raphe region appear to regulate cutaneous blood flow responses occurring as part of the response to painful or dangerous environmental events and as part of the regulation of body temperature.

Amygdala↗
PubMed2001

Cutaneous vasoconstriction contributes to hyperthermia induced by 3,4-methylenedioxymethamphetamine (ecstasy) in conscious rabbits.

3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy") increases body temperature. This process could be associated with increased cutaneous blood flow, as normally occurs with exercise-induced hyperthermia. Alternatively, an MDMA-induced fall in cutaneous blood flow could contribute to the hyperthermia by diminishing normal heat transfer from the body to the environment. We investigated these possibilities by administering MDMA (1.5-6 mg/kg, i.v.) to conscious freely moving rabbits, determining effects on body temperature, cutaneous blood flow (measured by a Doppler ultrasonic probe that was chronically implanted around the ear pinna artery), and other cardiovascular parameters. MDMA caused a dose-dependent increase in body temperature (from 38.3 +/- 0.3 to 41.2 +/- 0.4 degrees C after 6 mg/kg; p < 0.01; n = 5), preceded and accompanied by a dose-dependent cutaneous vasoconstriction (from 29 +/- 6 to 5 +/- 1 cm/sec after 6 mg/kg; p < 0.01; n = 5). MDMA (3 mg/kg) did not change blood flow to the mesenteric vascular bed. Prior unilateral cervical sympathectomy reduced the increase in body temperature elicited by MDMA (6 mg/kg) from 2.0 +/- 0.2 to 1.3 +/- 0.2 degrees C (p < 0.01; n = 5). On the denervated side, ear pinna blood flow after MDMA injection was 13 +/- 3 cm/sec, compared with 3 +/- 1 cm/sec on the sympathetically intact side (p < 0.05; n = 5). Thus, sympathetically mediated cutaneous vasoconstriction is one mechanism whereby MDMA causes hyperthermia. Reversal of cutaneous vasoconstriction by appropriate pharmacological means could be of therapeutic benefit in humans suffering from life-threatening hyperthermia induced by MDMA.

Animals↗
PubMed2001

Neurons in amygdala mediate ear pinna vasoconstriction elicited by unconditioned salient stimuli in conscious rabbits.

We determined whether functional integrity of neurons in the amygdala is necessary for sudden episodes of cutaneous vasoconstriction that occur when the conscious animal detects a salient alerting stimulus. To inhibit neuronal function, muscimol (5 nmol in 300 nl), a long acting and potent GABA-A receptor agonist that hyperpolarizes neurons, was injected bilaterally into the amygdala or into a more dorsal control site in conscious rabbits. Cutaneous blood flow was measured in the ear pinna flow using an ultrasonic Doppler probe chronically implanted around the central ear artery. Ear flow responses to salient unconditioned alerting stimuli (fur touch, slight cage movement. removal of drape covering cage) were examined before and after injection of the muscimol, and the effects compared with effects of muscimol on the ear flow response to more nociceptive stimuli, including ear pinch. Muscimol injections into the dorsal control site did not significantly alter alerting-related episodes of ear pinna vasoconstriction. Muscimol injections into the amygdala almost completely abolished ear vasoconstriction elicited by fur touch (0/5 positive responses), drape removal (0/7 positive responses) and cage movement (0/7 positive responses). Muscimol injections into the amygdala reduced the mean ear flow coefficient of variation for a 15 min observation period from 47+/-5 before injection to 15+/-33% after injection (P<0.01, n=7 rabbits). Muscimol injections into the amygdala did not alter the vigorous ear pinna vasoconstriction elicited by ear pinch (7/7 positive responses). Our results indicate that neuronal function in the amygdala, probably the central nucleus of the amygdala, is necessary for the occurrence of ear pinna vasoconstriction episodes elicited by unconditioned salient stimuli but not for the occurrence of corresponding vasoconstriction elicited by nociceptive stimuli.

Amygdala↗
PubMed2001

Raphe region mediates changes in cutaneous vascular tone elicited by stimulation of amygdala and hypothalamus in rabbits.

Raphe pallidus/parapyramidal neurons control cutaneous vasoconstriction induced by noxious stimuli. To determine whether they mediate forebrain-induced cutaneous vasoconstriction, we assessed changes in ear pinna blood flow elicited by electrical stimulation of amygdala and hypothalamus before and after injection of muscimol into the raphe/parapyramidal region. We compared ear flow with simultaneously recorded mesenteric flow. Experiments were performed in rabbits anesthetized with urethane (1.25-1.5 g/kg), paralysed and mechanically ventilated. Amygdala stimulation reduced skin conductance from 0.32+/-0.06 to 0.10+/-0.02 cm/s per mmHg (P<0.05, n=9), without effect on mesenteric conductance. Hypothalamic stimulation caused vasoconstriction in both cutaneous and mesenteric beds (conductances fell from 0.27+/-0.05 to 0.05+/-0.02 cm/s per mmHg and from 0.27+/-0.06 to 0.14+/-0.04 cm/s per mmHg (P<0.05, n=9), respectively). Muscimol microinjection (5 nmol in 100 nl) to raphe/parapyramidal region eliminated amygdala- and hypothalamus-induced skin vasoconstriction (pre-stimulus conductance 0.42+/-0.13 and 0.41+/-0.11 cm/s per mmHg, post-stimulus 0.41+/-0.12 and 0.39+/-0.10 cm/s per mmHg, respectively), but not hypothalamically-induced mesenteric vasoconstriction (pre-stimulus 0.29+/-0.06, post-stimulus 0.16+/-0.03 cm/s per mmHg, P<0.05, n=8). The latter was strongly attenuated by bilateral injection of muscimol to the rostral ventrolateral medulla. Data suggest that descending hypothalamo-spinal and amygdala-spinal pathways constricting the cutaneous vascular bed relay in the raphe/parapyramidal area. A relay in the rostral ventrolateral medulla contributes substantially to mesenteric vasoconstriction elicited from the hypothalamus.

Amygdala↗
PubMed2001

Tail artery blood flow measured by chronically implanted Doppler ultrasonic probes in unrestrained conscious rats.

We describe a surgical procedure for chronically implanting a Doppler ultrasonic probe around the tail artery of the rat to measure phasic flow velocity in the tail artery of the unrestrained conscious rat. The phasic tail flow signal is highly correlated with the simultaneously recorded superior mesenteric flow signal (range 0.70-0.89 in seven rats) during vasoconstriction induced by exposure to formaldehyde vapour. In response to two quick alerting taps on the cage, tail flow velocity fell from 20+/-2 to 7+/-1 cm/s (P<0.01) and mesenteric flow fell from 30+/-5 to 25+/-4 cm/s (P<0.05), with the fall in tail flow being significantly greater than the fall in mesenteric flow (P<0.05, n=7 rats). In anesthetized rats, the phasic tail flow signal was highly correlated with phasic arterial pressure (range 0.71-0.83 in seven rats). The ability to reliably measure phasic arterial tail flow in the conscious unrestrained rat should facilitate experimental studies of brain pathways regulating flow to this principally cutaneous vascular bed in different physiological situations.

Animals↗
PubMed2001

Raphe magnus/pallidus neurons regulate tail but not mesenteric arterial blood flow in rats.

In urethane-anesthetized rats with body temperature maintained at 39-40 degrees C, electrical stimulation of raphe magnus/pallidus/parapyramidal region within 0.5 mm of the ventral medullary surface reduced arterial blood flow to the tail cutaneous bed (measured with a chronically implanted Doppler ultrasonic flowmeter) from 28+/-5 to 6+/-1 cm/s (P<0.01), without changing mesenteric arterial blood flow, and with only small, variable changes in arterial pressure. Injection of bicuculline (50 pmol in 50 nl) at the same site reduced tail flow from 19+/-2 to 3+/-1 cm/s (P<0.01), again without significantly changing mesenteric flow, but with a moderate increase in arterial pressure. When the rat was cooled to reduce basal tail blood flow, injection of muscimol (1 nmol in 100 nl) or GABA (100 nmol in 100 nl) into the raphe site restored tail blood flow to 93+/-4% of the pre-cooling level. These recordings are the first reported direct measurements of rat tail blood flow changes elicited by alteration of neuronal function in the brainstem. The rostral medullary raphe controls the tail cutaneous vascular bed in a relatively selective manner. Our findings add to evidence that raphe magnus/pallidus/parapyramidal neurons are involved in regulating cutaneous blood flow in response to changes in body temperature in the rat.

Animals↗