Biomedical subjects

W T Talman

Publications and source records attributed to W T Talman.

At least 37 records · Page 2Linked to original sources

PubMed1997

Role of endogenous carbon monoxide in central regulation of arterial pressure.

We investigated the contribution of neural mechanisms to the arterial pressure increase produced by zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG), an inhibitor of endogenous carbon monoxide synthesis. The arterial baroreceptor reflex control of heart rate was examined in rats with and without ZnDPBG pretreatment (45 micromol/kg IP) by analysis of the arterial pressure-heart rate relationship during infusions of phenylephrine or sodium nitroprusside to vary arterial pressure. ZnDPBG increased arterial pressure from 110 +/- 3 to 126 +/- 2 mm Hg without eliciting bradycardia. The maximum gain of the heart rate response to changes in arterial pressure was attenuated by ZnDPBG treatment (-1.9 +/- 0.3 versus -4.8 +/- 1.0 bpm/mm Hg). The possibility that ZnDPBG elevates arterial pressure by attenuating baroreceptor reflex function was addressed by comparing the pressor response to ZnDPBG (45 micromol/kg IP) in rats with and without sinoaortic denervation. The pressor effect of ZnDPBG was similar in rats with and without arterial baroreceptor deafferentation, implying that the increase in pressure is not simply the consequence of attenuated baroreceptor reflex function per se. The possibility that ZnDPBG increases arterial pressure via an effect on the nucleus tractus solitarii (NTS) also was investigated. ZnDPBG (1 nmol in 100 nL) injected into the NTS of rats increased arterial pressure from 111 +/- 4 to 126 +/- 5 mm Hg, and this effect was reversed by an ipsilateral microinjection of carbon monoxide into the NTS. Accordingly, the pressor effect of ZnDPBG may rely on inhibition of carbon monoxide production in the NTS. This implies that carbon monoxide formed by brain heme oxygenase plays a role in the central regulation of arterial pressure.

Animals↗

PubMed1997

Glutamatergic transmission in the nucleus tractus solitarii: from server to peripherals in the cardiovascular information superhighway.

Afferent nerves carrying signals from mechanoreceptors in the aortic arch and carotid sinus terminate predominantly in the nucleus tractus solitarii (NTS). Signal transduction and neurotransmission in the NTS are critical for central cardiovascular reflect control, but little was known about either until the late 1970's. None of the numerous neuroactive chemicals found in the NTS had met strict criteria as a neurotransmitter in the baroreflex arc until data suggested that the excitatory amino acid L-glutamate (GLU) might be released from baroreceptor afferent terminals in the NTS. In anesthetized animals microinjection into the NTS of GLU, which can be demonstrated in terminals in the NTS, produces cardiovascular responses like those seen with activation of the baroreceptor reflex. Similar responses occur in awake animals if the chemoreceptor reflex is eliminated; otherwise, in conscious animals responses mimic those of chemoreceptor reflect activation. GLU released in the NTS upon selective activation of the baroreceptor, and possibly the chemoreceptor, reflex. Responses to selective agonists as well as baroreflex responses are eliminated by GLU antagonists microinjected into the NTS. Non-NMDA (N-methyl-D-aspartic acid) receptors seem to predominate at primary baroreceptor synapses in the NTS while NMDA receptors may be involved at later synapses. Although inhibition of soluble guanylate cyclase attenuates responses to ionotropic glutamate agonists in the NTS, nitric oxide does not seem to play a role in glutamate transmission in the NTS. GLU may also participate in transmission at cardiovascular neurons beyond the NTS. For example, a role has been suggested for GLU in the ventrolateral medulla and spinal cord. Work continues concerning GLU signal transduction and mechanisms that modulate that transduction both at the NTS and at other cardiovascular nuclei.

Baroreflex↗

PubMed1997

The myth of nitric oxide in central cardiovascular control by the nucleus tractus solitarii.

Considerable evidence suggests that nitroxidergic mechanisms in the nucleus tractus solitarii (NTS) participate in cardiovascular reflex control. Much of that evidence, being based on responses to nitric oxide precursors or inhibitors of nitric oxide synthesis, has been indirect and circumstantial. We sought to directly determine cardiovascular responses to nitric oxide donors microinjected into the NTS and to determine if traditional receptor mechanisms might account for responses to certain of these donors in the central nervous system. Anesthetized adult Sprague Dawley rats that were instrumented for recording arterial pressure and heart rate were used in the physiological studies. Microinjection of nitric oxide itself into the NTS did not produce any cardiovascular responses and injection of sodium nitroprusside elicited minimal depressor responses. The S-nitrosothiols, S-nitrosoglutathione (GSNO), S-nitrosoacetylpenicillamine (SNAP), and S-nitroso-D-cysteine (D-SNC) produced no significant cardiovascular responses while injection of S-nitroso-L-cysteine (L-SNC) elicited brisk, dose-dependent depressor and bradycardic responses. In contrast, injection of glyceryl trinitrate elicited minimal pressor responses without associated changes in heart rate. It is unlikely that the responses to L-SNC were dependent on release of nitric oxide in that 1) the responses were not affected by injection of oxyhemoglobin or an inhibitor of nitric oxide synthesis prior to injection of L-SNC and 2) L- and D-SNC released identical amounts of nitric oxide when exposed to brain tissue homogenates. Although GSNO did not independently affect blood pressure, its injection attenuated responses to subsequent injection of L-SNC. Furthermore, radioligand binding studies suggested that in rat brain synaptosomes there is a saturable binding site for GSNO that is displaced from that site by L-SNC. The studies suggest that S-nitrosocysteine, not nitric oxide, may be an interneuronal messenger for cardiovascular neurons in the NTS.

Animals↗

PubMed1996

Commissural nucleus of the solitary tract lesions reduce food intake and body weight gain in rats.

This study investigated the effects of an electrolytic lesion of the commissural subnucleus of the nucleus of the solitary tract (commNTS) on body weight, daily food and water intake, and plasma glucose and insulin in rats. In the first 6 days following brain surgery, commNTS lesioned rats reduced daily food intake by 80% compared to rats with sham lesions. After this period rats with lesions of commNTS started recovering food intake, but intake remained significantly reduced until the 12th day after surgery. A reduction in body weight was observed 4 days after surgery and reached a maximum on the 12th day. After this, a partial recovery of body weight was observed, but weight remained significantly reduced compared to weights of rats with sham lesions through the conclusion of the study. Food intake and body weight gain in other rats with partial lesions of the commNTS or with lesions outside the commNTS did not differ from rats with sham lesions with regard to those variables. Daily water intake and plasma glucose and insulin were not changed by the commNTS lesions. These results suggest that commNTS is involved with mechanisms that control food intake and body weight in rats.

Animals↗

PubMed1996

Release of glutamate in the nucleus tractus solitarii in response to baroreflex activation in rats.

Release of endogenous aspartate and glutamate from the region of the nucleus tractus solitarii was measured in vitro by perfusion methods and in vivo by microdialysis. Stimulation of the nucleus tractus solitarii with 35 mM potassium in vitro significantly increased extracellular concentrations of aspartate and glutamate. Glutamate and aspartate concentrations also increased with dialysis of 100 mM KCl into the nucleus tractus solitarii in vivo, but only changes in glutamate were significant. Experiments in vivo revealed that activation of the baroreflex by intravenous infusion of phenylephrine significantly increased glutamate in dialysates, while hypoventilation that accompanies baroreceptor activation and may activate chemoreceptors tended to increase aspartate but not glutamate. The demonstration that glutamate, but not aspartate, is released with activation of the baroreflex further supports the hypothesis that glutamate is a neurotransmitter of baroreceptor afferents terminating in the nucleus tractus solitarii.

Animals↗

PubMed1996

Commissural NTS contributes to pressor responses to glutamate injected into the medial NTS of awake rats.

In the present study we investigated whether interruption of the chemoreceptor reflex by an electrolytic lesion of the commissural subnucleus of the nucleus tractus solitarii (commNTS) influenced pressor and bradycardic responses induced by microinjection of L-glutamate (L-Glu) into the medial NTS (mNTS) of conscious rats. Seven days after sham lesions, seven rats demonstrated significant pressor [change in mean arterial pressure (MAP) = +33 +/- 3 mmHg] and bradycardic [change in heart rate (HR) = -74 +/- 8 beats/min (bpm)] responses to chemoreceptor reflex activation by intravenous injection of KCN. Likewise, L-Glu (1 nmol in 100 nl) injected into the mNTS in sham rats induced pressor (+29 +/- 2 mmHg) and bradycardic responses (-90 +/- 8 bpm). However, in 11 rats with lesions in commNTS, pressor and bradycardic chemoreceptor reflex responses were abolished, and injection of L-Glu into the mNTS decreased MAP (-14 +/- 6 mmHg) and HR (-59 +/- 16 bpm) as is reported in anesthetized control rats. We conclude that pressor responses induced by L-Glu microinjected into the baroreceptor reflex region of mNTS in conscious rats depend on the integrity of the commNTS, which plays an important role in central chemoreceptor reflex pathways.

Animals↗

PubMed1995

Denervation supersensitivity to glutamate in the nucleus tractus solitarii after removal of the nodose ganglion.

If L-glutamate (L-Glu) is the transmitter released from cardiovascular vagal afferent nerve fibers in the nucleus tractus solitarii (NTS), then interruption of those afferents should lead to denervation supersensitivity to L-Glu in the NTS. Therefore, we sought to determine if dose-related changes in arterial pressure (AP) and heart rate (HR) elicited by L-Glu microinjected into the NTS evolve after removal of the left nodose ganglion in rats. Twelve rats served as unoperated controls; and eight were studied 5 days, eleven 10 days, and nine 15 days after ganglionectomy. Each rat was anesthetized with halothane (1.5-2.0%) and cannulated for recording AP and HR. After exposure of the brainstem, vehicle or L-Glu (3, 30, 75, 150, 300 and 1500 pmol/50 nl) was microinjected alternately into the right and left dorsomedial NTS. In control animals, and in animals 5 days and 15 days after ganglionectomy, the lowest dose of L-Glu that produced a significant fall of mean AP (-10 +/- 2, -5 +/- 2, -6 +/- 1 mmHg, respectively) was 30 pmoles. The threshold dose with injections on the lesioned side 10 days after ganglionectomy was 3 pmol (-8 +/- 2 mmHg). In rats studied at 10 days, but not in control, 5 or 15 days rats, the dose-responses for injections made on the left were shifted significantly to the left of those made on the right (P < 0.05). In control, 5, and 15 day rats there were no significant differences between dose-related responses elicited from right and left NTS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Inhibition of nitric oxide synthesis extends cerebrovascular autoregulation during hypertension.

In anesthetized intact rats, cerebral blood flow is autoregulated until mean arterial blood pressure (MAP) exceeds 150 mmHg. At higher pressures cerebral blood flow breaks through autoregulation and rapidly increases. However, interruption of the arterial baroreceptor reflex eliminates breakthrough of autoregulation. Thus, breakthrough may reflect active rather than passive vasodilatation. We, therefore, sought to determine if breakthrough depends upon synthesis of the vasodilator nitric oxide. Thirty-eight anesthetized adult male Sprague-Dawley rats were studied. In all, MAP was raised by slow i.v. infusion of phenylephrine. In rats pretreated with the nitric oxide synthase inhibitor L-nitroarginine (L-NA; 22 mg/kg i.v.) or with a combination of L-NA plus D-arginine (D-Arg; 240 mg/kg i.v.), breakthrough did not occur even when MAP exceeded 185 mmHg (L-NA) and 165 mmHg (D-Arg). In contrast, breakthrough occurred in rats treated with L-NA plus L-arginine (L-Arg; 240 mg/kg i.v.) and in rats whose basal vascular tone had been increased by pretreatment with arginine vasopressin prior to infusion of phenylephrine. Removal of sympathetic innervation to cerebral vessels attenuated, but did not eliminate, effects of L-NA on breakthrough. Thus, vasodilatation seen with breakthrough of autoregulation depends upon release of nitric oxide or a nitric oxide donor.

Animals↗

PubMed1995

Evolution of dose-related cardiovascular responses to L-glutamate microinjected into the nucleus tractus solitarii after removal of the nodose ganglion in rat.

1. In this study, we sought to determine if sensitivity to dose-related changes in arterial pressure (AP) and heart rate (HR) elicited by microinjection of L-glutamate (L-GLU) into the nucleus tractus solitarii (NTS) evolves after deafferentation in adult male Sprague-Dawley rats. 2. Twelve rats served as unoperated controls; and eight were studied 5 days, eleven 10 days and nine 15 days after ganglionectomy. Each rat was anaesthetized (halothane 1.5-2.0%) and cannulated for recording AP and HR. Vehicle or L-GLU (3, 30, 75, 150, 300 and 1500 pmole/50 nL) was microinjected into the right and left NTS. Injection sites were confirmed histologically. 3. In control animals and in animals 5 days and 15 days after ganglionectomy, the lowest dose of L-GLU that produced a significant fall of AP was 30 pmole. The threshold dose with injections on the lesioned side 10 days after ganglionectomy was 3 pmole. In rats studied at 10 days, but not in control, 5 or 15 day rats, dose-related responses for injections made on the left were shifted significantly to the left of those made on the right (P < 0.05). 4. In control, 5 and 15 day rats there were no significant differences between dose-related responses elicited from right and left NTS. Responses of HR did not differ between groups of animals or sides of injection. 5. These results suggest that supersensitivity to L-GLU evolves after nodose ganglionectomy and support a role for L-GLU as a transmitter of cardiovascular afferents in the NTS.

Anesthesia↗

PubMed1995

Alteration of baroreceptor and chemoreceptor reflexes in spontaneously hypertensive rats.

1. Electrical stimulation of the aortic depressor nerve elicited depressor and bradycardiac responses in both spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats, but in spontaneously breathing animals responses were weaker in SHR than in WKY. 2. Responses did not significantly differ in artificially ventilated animals except that high stimulation intensity elicited significantly greater bradycardiac responses in WKY. A decrease in ventilatory rate occurred in both strains. 3. Electrical stimulation of the carotid sinus nerve (CSN) elicited an initial pressor response followed by a depressor response with a minimal change in heart rate in either strain. The pressor response in SHR was greater than in WKY. Depressor responses in SHR were weaker than those in WKY with or without artificial ventilation. CSN stimulation increased ventilatory rate in both strains but the frequency-related responses differed at higher stimulation intensity. 4. These results suggest that there are alterations in the function of central or afferent components of chemoreceptor and baroreceptor reflexes in SHR in addition to previously described structural changes at the level of peripheral sensory receptors.

Animals↗

PubMed1995

Baroreceptors in the carotid sinus contribute to arterial baroreceptor reflexes in normotensive rats.

1. Baroreceptor reflex influences on renal sympathetic nerve activity (RSNA) were estimated with non-linear regression analysis (sigmoidal curve fitting) before and after transection of carotid sinus nerves (CSN) and aortic depressor nerves (ADN) in rats. 2. Transection of ADN reduced the gain of the reflex to 42% of basal levels with increases in arterial pressure (MAP) and RSNA. Subsequent transection of CSN eliminated the remaining sigmoidal correlation between MAP and RSNA without further changes in resting MAP and RSNA. 3. By comparison, the transection of CSN reduced the gain of the reflex to 53% of basal levels without affecting other variables. Additional transection of both ADN eliminated the remaining sigmoidal correlation between MAP and RSNA with further increases in resting MAP and RSNA. 4. These results indicate that carotid sinus baroreceptors exist in rats. They contribute to baroreceptor-mediated reflex changes in RSNA as do aortic baroreceptors, although the working range of MAP may increase with transection of the latter.

Animals↗

PubMed1995

Mechanisms for preserved cerebrovascular autoregulation during hypertension in rats after sinoaortic denervation.

1. Cerebral blood flow (CBF) and cerebrovascular resistance (CVR) autoregulate to higher levels of arterial pressure (AP) in rats after sinoaortic denervation (SAD) than in intact rats. 2. Potential mechanisms for this phenomenon were studied by monitoring CBF by laser flowmetry while increasing AP in rats after: (i) SAD; (ii) SAD plus bilateral removal of the superior cervical ganglia; (iii) SAD plus interruption of all renal vessels and nerves (renal isolation); (iv) SAD plus sympathectomy and renal isolation; and (v) intravenous treatment with the nitric oxide synthase inhibitor L-nitroarginine (LNA). 3. Compared to intact control rats autoregulation persisted to higher absolute levels of AP in SAD rats with isolation of the kidneys and resistance did not fall significantly below that in rats with SAD alone. 4. Effects of SAD on autoregulation were not altered by combining renal isolation with an interruption of sympathetics. 5. LNA did not affect the baroreflex but blocked a breakthrough of autoregulation even at a maximal mean AP (MAP) of 189 +/- 2 mmHg. 6. Breakthrough occurred in animals pretreated with LNA plus L-arginine but not in animals given LNA plus D-arginine. 7. These data are consistent with a role of the baroreflex in the expression of breakthrough and suggest that breakthrough may result from release of nitric oxide or a nitric oxide donor.

Animals↗

PubMed1994

Glycine elicits release of acetylcholine from the nucleus tractus solitarii in rat.

Previous studies have suggested that cardiovascular responses elicited by injection of glycine into the nucleus tractus solitarii (NTS) depend upon interactions between glycinergic and cholinergic neuronal elements in NTS. Release of acetylcholine in response to glycine is one such interaction that has been shown in slices of hippocampus and striatum. In this study we sought to test the hypothesis that glycine causes release of acetylcholine from neurotransmitter stores in NTS. We compared release from NTS with that from adjacent hypoglossal nucleus and from caudate nucleus. Release of radiolabeled acetylcholine was determined in vitro after incubating NTS with [3H]choline. Exposure of NTS and caudate nucleus, but not hypoglossal nucleus, to glycine caused release of acetylcholine in a calcium-dependent manner that varied with concentration of glycine in the incubation medium. The maximally effective concentration (1 mM) of glycine elicited 136% increases over basal levels. Glycine did not elicit release of [3H]acetylcholine from tissue when calcium ion had been removed from the bath. Acetylcholine also was not released if tissue was incubated with either strychnine (10 microM) or hemicholinium-3 (1 mM) prior to exposure to glycine (1 mM). Thus, glycine, acting at strychnine-sensitive receptors in NTS, elicits release of acetylcholine from a portion of locally synthesized neurotransmitter stores.

Acetylcholine↗

PubMed1994

Baroreflexes influence autoregulation of cerebral blood flow during hypertension.

Cerebral blood flow (CBF) is autoregulated at mean arterial pressures (MAP) ranging from approximately 50 to 150 mmHg. When MAP exceeds the upper limit, autoregulation breaks through, vasodilatation occurs, and CBF increases rapidly. Earlier studies have shown that the arterial baroreflex does not influence autoregulation. However, CBF may rise to a lesser degree during abrupt hypertension immediately after interruption of the baroreceptor reflex than it would at comparable levels of blood pressure in intact animals. Generally this shift of the breakthrough point has been attributed to an increase in sympathetic nerve activity immediately after sinoaortic denervation. We hypothesized that denervation of arterial baroreceptors would blunt vasodilatation during slow controlled increases of arterial pressure, and we sought to determine whether sympathetic nerves contributed to regulation of CBF during hypertension in baroreceptor-denervated animals. Thirty-eight rats were studied to determine whether sinoaortic denervation affected autoregulation or breakthrough during acute hypertension. In five intact rats, when arterial pressure was raised by phenylephrine to 155 +/- 4 mmHg, cerebrovascular resistance fell by 60% and CBF increased by 434%. After interruption of the baroreflex in six rats, such dramatic increases in CBF with breakthrough did not occur despite greater increases in MAP (to 185 +/- 2 mmHg). Similar results were obtained when arterial pressure was raised by infusion of arginine vasopressin in four intact and three denervated rats. The effects of baroreceptor reflex interruption were not significantly affected by bilateral removal of the superior cervical ganglia. Rates of rise of MAP and increases of pulse pressure were equivalent between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Both NMDA and non-NMDA receptors in the NTS participate in the baroreceptor reflex in rats.

In this study, we determined whether either N-methyl-D-aspartate (NMDA) receptors or non-NMDA receptors in the nucleus tractus solitarii (NTS) participate in the baroreceptor reflex in rats. Microinjection of an NMDA receptor antagonist, MK-801, and a non-NMDA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione, into the NTS decreased the sensitivity of the baroreceptor reflex by 51 and 41%, respectively. Simultaneous administration of both agents further reduced the sensitivity of the baroreceptor reflex to 28% of control. A competitive NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid, also attenuated reflex bradycardia or tachycardia elicited by a single dose of phenylephrine or nitroprusside, respectively. Specificity of each antagonist's effects was supported by selective blockade of depressor responses produced by agonists that act at the NMDA and non-NMDA receptors, respectively. Results of this study indicate that both non-NMDA- and NMDA-sensitive receptors are involved in baroreceptor reflex transmission in the NTS.

2-Amino-5-phosphonovalerate↗

PubMed1994

Hemodynamic effects elicited by stimulation of the nucleus tractus solitarii.

Microinjection of the excitatory amino acid L-glutamate into the nucleus tractus solitarii (NTS) elicits decreases in arterial pressure and heart rate. In the present study, we sought to determine the regional hemodynamic effects that were correlated with changes in arterial pressure and heart rate produced by stimulation of the NTS. In anesthetized rats, blood flow in the renal (RBF), superior mesenteric (MBF), and hindquarter (HBF) vascular beds was measured by pulsed Doppler flowmeters. Relative vascular resistances (RVR, MVR, and HVR) were calculated by dividing mean arterial pressure (mm Hg) by the Doppler shift (kHz). Microinjection of L-glutamate into the NTS caused rapid, transient, dose-related decreases in mean arterial pressure and heart rate. MVR and RVR were minimally changed immediately after injections, but both demonstrated delayed dilatation. In contrast, HVR fell immediately but demonstrated delayed constriction. Identical changes occurred in intact rats and in those with interruption of the baroreflex by sinoaortic denervation. Ganglionic blockade with hexamethonium abolished virtually all L-glutamate-induced responses. This study suggests that NTS neurons exert differential effects on renal, mesenteric, and hindquarter vascular beds and that glutamate-induced regional hemodynamic changes are mediated predominantly through autonomic pathways.

Animals↗

PubMed1993

Spermidine and cardiovascular control in nucleus tractus solitarii in rat.

Cardiovascular effects elicited by unilateral microinjection of polyamines into the nucleus tractus solitarii (NTS) were tested in anesthetized rats. Spermidine (50-900 pmol) produced dose-dependent depressor and bradycardiac responses that were similar to those elicited by N-methyl-D-aspartate (NMDA; 0.1-1.2 pmol). The polyamines, putrescine and spermine, did not produce significant cardiovascular responses. The cardiovascular responses induced by spermidine and NMDA were almost eliminated by prior injection of the noncompetitive NMDA antagonist MK801 into NTS. On the other hand, a competitive antagonist 2-amino-5-phosphonovaleric acid (APV) blocked responses to NMDA but only attenuated those to spermidine. These findings support an action of the polyamine spermidine at the NMDA receptor complex in NTS where it could participate in modulating cardiovascular activity.

2-Amino-5-phosphonovalerate↗

PubMed1993

Neural control of the heart. Central and peripheral.

The central nervous system through its modulation of autonomic activity plays an important role in maintaining homeostasis in the cardiovascular system and in integrating cardiovascular responses with behaviors. Thus, central and autonomic disturbances can lead to profound alterations in cardiac function manifested by cardiac arrhythmias and signs of myocardial injury. These disturbances can further compromise patients with primary central lesions. Rapid recognition and appropriate treatment of the cardiac complications as well as the underlying condition are critical for effective management of many such patients.

Arrhythmias, Cardiac↗