Activation of neurons in the rostral ventrolateral medulla increases bronchomotor tone in dogs

1991 ◽  
Vol 71 (1) ◽  
pp. 210-216 ◽  
Author(s):  
J. R. Haselton ◽  
P. A. Padrid ◽  
M. P. Kaufman
Keyword(s):  
Smooth Muscle ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Ventrolateral Medulla ◽  
Adrenergic Blockade ◽  
Homocysteic Acid ◽  
Lung Resistance ◽  
Anesthetized Dogs ◽  
Total Lung Resistance ◽  
Bronchomotor Tone

Previous work from this laboratory has demonstrated that the chemical activation of cell bodies in the caudal ventrolateral medulla of chloralose-anesthetized dogs decreased bronchomotor tone by withdrawing cholinergic input to airway smooth muscle. In the present study we determined the bronchomotor responses to microinjection of DL-homocysteic acid (100 mM; 25–50 nl) into the rostral ventrolateral (RVL) medulla of chloralose-anesthetized dogs. Total lung resistance was used as a functional index of bronchomotor tone. Microinjection of DL-homocysteic acid into the 20 sites located in the lateral aspect of the RVL medulla increased both total lung resistance [from 6.5 +/- 0.4 to 9.1 +/- 0.8 (SE) cmH2O.l-1.s; P less than 0.05] and mean arterial pressure (from 125 +/- 5 to 148 +/- 8 mmHg; P less than 0.05). Microinjection of this amino acid into nine sites located in the medial aspect of the RVL medulla increased mean arterial pressure (from 130 +/- 6 to 153 +/- 6 mmHg; P less than 0.05) but had no effect on total lung resistance. We confirmed in three sites that the increase in total lung resistance evoked by microinjection of DL-homocysteic acid was accompanied by an increase in tracheal smooth muscle tension. The increase in total lung resistance evoked by DL-homocysteic acid was not affected by beta-adrenergic blockade but was abolished by muscarinic blockade.

Stimulation of the caudal ventrolateral medulla decreases total lung resistance in dogs

1987 ◽  
Vol 63 (3) ◽  
pp. 912-917 ◽  
Author(s):  
J. C. Connelly ◽  
L. W. McCallister ◽  
M. P. Kaufman
Keyword(s):  
Electrical Stimulation ◽  
Nucleus Ambiguus ◽  
Ventrolateral Medulla ◽  
Adrenergic Blockade ◽  
Homocysteic Acid ◽  
Caudal Ventrolateral Medulla ◽  
Airway Caliber ◽  
Lung Resistance ◽  
Total Lung Resistance ◽  
Stimulation Of

Although the role played by the caudal ventrolateral medulla in the regulation of the cardiovascular system has been extensively investigated, little is known about the role played by this area in the regulation of airway caliber. Therefore, in alpha-chloralose-anesthetized dogs, we used both electrical and chemical means to stimulate the caudal ventrolateral medulla while we monitored changes in total lung resistance breath by breath. We found that electrical stimulation (25 microA) of 26 sites in this area significantly decreased total lung resistance from 7.1 +/- 0.4 to 5.7 +/- 0.3 cmH2O.1'1.s (P less than 0.001). The bronchodilation evoked by electrical stimulation was unaffected by beta-adrenergic blockade but was abolished by cholinergic blockade. In addition, chemical stimulation of seven sites in the caudal ventrolateral medulla with microinjections of DL-homocysteic acid (0.2 M; 66 nl), which stimulates cell bodies but not fibers of passage, also decreased total lung resistance from 8.3 +/- 1.1 to 6.5 +/- 0.8 cmH2O.l'1.s (P less than 0.01). In contrast, microinjections of DL-homocysteic acid into the nucleus ambiguus (n = 6) increased total lung resistance from 7.5 +/- 0.5 to 9.2 +/- 0.4 cmH2O.l'1.s (P less than 0.05). We conclude that the caudal ventrolateral medulla contains a pool of cell bodies whose excitation causes bronchodilation by withdrawing cholinergic input to airway smooth muscle.

Stimulation of parabrachial nuclei dilates airways in cats

1994 ◽  
Vol 76 (4) ◽  
pp. 1712-1718 ◽  
Author(s):  
A. M. Motekaitis ◽  
I. C. Solomon ◽  
M. P. Kaufman
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Dynamic Compliance ◽  
Baroreceptor Reflex ◽  
Homocysteic Acid ◽  
Airway Caliber ◽  
Lung Resistance ◽  
Parabrachial Nuclei ◽  
Total Lung Resistance ◽  
Stimulation Of

Stimulation of the parabrachial nuclei has been shown to increase mean arterial pressure as well as to terminate inspiration. Nevertheless, the effect on airway caliber evoked by stimulation of the parabrachial nuclei is not known. Therefore, in chloralose-anesthetized cats, we microinjected DL-homocysteic acid (25 nl; 100 mM) into 44 sites in or near the lateral and medial parabrachial nuclei while calculating breath-by-breath total lung resistance and dynamic compliance. We found that, in 43 of these sites, microinjection of this excitatory amino acid consistently decreased total lung resistance but had no effect on dynamic compliance. The decrease in lung resistance was caused by a withdrawal of cholinergic tone to the airways. We could find no evidence that the decrease in total lung resistance evoked by stimulation of the parabrachial nuclei was caused by activation of either beta-adrenergic or nonadrenergic noncholinergic pathways. The decrease in total lung resistance evoked by stimulation of the parabrachial nuclei was not secondary to the baroreceptor reflex even though microinjection frequently increased mean arterial pressure. In addition, microinjection did not have consistent effects on phrenic nerve activity, although in individual circumstances the effect on this activity was quite large. We conclude that stimulation of cell bodies and dendrites in the parabrachial nuclei dilates the airways of anesthetized cats and that the effect is not secondary to the baroreceptor reflex.

Stimulation of splanchnic afferents reflexly relaxes tracheal smooth muscle in dogs

1983 ◽  
Vol 55 (2) ◽  
pp. 427-432 ◽  
Author(s):  
K. J. Rybicki ◽  
J. C. Longhurst ◽  
M. P. Kaufman
Keyword(s):  
Smooth Muscle ◽  
Small Intestine ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Visceral Pain ◽  
Muscle Tension ◽  
Tracheal Smooth Muscle ◽  
Visceral Afferents ◽  
Anesthetized Dogs ◽  
Stimulation Of

Although chemical stimulation of abdominal visceral afferents has been shown to reflexly increase cardiovascular and ventilatory function, the effect of stimulating these afferents on airway smooth muscle is unknown. Therefore, we recorded transverse smooth muscle tension from an innervated segment of trachea in chloralose-anesthetized dogs while we topically applied capsaicin (200 micrograms/ml) and bradykinin (0.01-10 micrograms/ml) to the serosal surfaces of the stomach, small intestine, and gallbladder. Application of these irritant substances to the stomach and small intestine decreased tracheal tension and increased mean arterial pressure. However, application of capsaicin and bradykinin to the gallbladder had only small effects on both of these variables. Cutting the splanchnic nerves abolished or greatly attenuated the decreases in tension and increases in mean arterial pressure, whereas cutting the vagi had no effect on them. We conclude that stimulation of splanchnic afferent endings in the stomach and small intestine reflexly relaxes tracheal smooth muscle in dogs. This effect may be one component of the constellation of autonomic responses reflexly evoked by abdominal visceral pain and inflammation.

Stimulation of H fields of Forel decreases total lung resistance in dogs

1988 ◽  
Vol 65 (5) ◽  
pp. 2156-2163 ◽  
Author(s):  
L. W. McCallister ◽  
J. C. Connelly ◽  
M. P. Kaufman
Keyword(s):  
Electrical Stimulation ◽  
Adrenergic Blockade ◽  
Functional Index ◽  
Nerve Activity ◽  
Homocysteic Acid ◽  
Airway Caliber ◽  
Lung Resistance ◽  
Cholinergic Tone ◽  
Total Lung Resistance ◽  
Stimulation Of

Although there is considerable evidence that the H fields of Forel of the posterior diencephalon play an important role in the regulation of cardiovascular function, little is known about the role these areas play in the control of airway caliber. In chloralose-anesthetized paralyzed dogs, we used both electrical and chemical means to stimulate the H fields of Forel, while we monitored breath-by-breath changes in total lung resistance (TLR), a functional index of airway caliber. Electrical stimulation (200-250 microA, 80 Hz, 0.75 ms) of 82 histologically confirmed sites significantly decreased TLR from 9.2 +/- 0.4 to 7.9 +/- 0.4 cmH2O.l-1.s (P less than 0.01). The bronchodilation evoked by electrical stimulation was unaffected by beta-adrenergic blockade with propranolol but was abolished by cholinergic blockade with atropine. The increases in airway caliber evoked by stimulation were often accompanied by increases in phrenic nerve activity. Chemical stimulation of 21 of 82 sites with microinjections of DL-homocysteic acid (83 nl, 0.2 and 0.5 M), which stimulates cell bodies but not fibers of passage, also decreased TLR from 8.3 +/- 0.5 to 7.3 +/- 0.5 cmH2O.l-1.s (P less than 0.03). We conclude that stimulation of cell bodies in the H fields of Forel produces bronchodilation by withdrawal of cholinergic tone to airway smooth muscle.

NMDA receptors in caudal ventrolateral medulla mediate reflex airway dilation arising from the hindlimb

1994 ◽  
Vol 77 (4) ◽  
pp. 1697-1704 ◽  
Author(s):  
I. C. Solomon ◽  
A. M. Motekaitis ◽  
M. K. Wong ◽  
M. P. Kaufman
Keyword(s):  
Electrical Stimulation ◽  
Sciatic Nerve ◽  
Nmda Receptors ◽  
Ventrolateral Medulla ◽  
Lung Resistance ◽  
Anesthetized Dogs ◽  
Sciatic Nerve Stimulation ◽  
Gastrocnemius Muscles ◽  
Total Lung Resistance ◽  
Stimulation Of

The caudal ventrolateral medulla (CVLM) has been shown to participate in the reflex airway dilation evoked by stimulation of thin fiber afferents innervating the hindlimb of anesthetized dogs. Nevertheless, the pharmacological mechanism in the CVLM by which hindlimb afferents evoke this reflex airway dilation is not known. Therefore, we examined the role played by excitatory amino acid receptors in the CVLM in the reflex airway dilation arising from the hindlimb. Using chloralose-anesthetized dogs, we found that bilateral microinjections into the CVLM of either (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (25 mM, 50 nl) or (+/-)-2-amino-5-phosphonovaleric acid (50 mM, 50 nl), both of which block N-methyl-D-aspartate (NMDA) receptors, reversibly attenuated the decrease in total lung resistance that was evoked by either electrical stimulation of C-fibers in the sciatic nerve or by static contraction of both gastrocnemius muscles. In contrast, bilateral microinjection into the CVLM of 6-cyano-7-nitroquinoxaline-2,3-dione (39 microM, 50 nl), which blocks non-NMDA receptors, augmented the reflex decrease in total lung resistance that was evoked by either sciatic nerve stimulation or contraction of the gastrocnemius muscles. Bilateral microinjections of xanthurenic acid (100 mM, 50 nl) into the CVLM had no effect on the decrease in total lung resistance that was evoked by sciatic nerve stimulation. We conclude that NMDA, but not non-NMDA, receptors in the CVLM play an important role in the reflex arc that dilates the airways when hindlimb afferents are stimulated by either muscular contraction or electrical stimulation.

Abstract 477: Diverse Actions of the EP4 Prostaglandin E2 Receptor in Blood Pressure Control

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Marcela Herrera ◽  
Matthew A Sparks ◽  
Beverky H Koller ◽  
Thomas M Coffman
Keyword(s):  
Smooth Muscle ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Smooth Muscle Cells ◽  
Prostaglandin E2 ◽  
Ductus Arteriosus ◽  
Muscle Cells ◽  
High Salt ◽  
Ang Ii ◽  
The Impact

Prostaglandin E2 (PGE2) is a major prostanoid produced by the kidney having the potential to influence renal blood flow, Na excretion, and thus mean arterial pressure (BP). PGE2 actions are mediated by four distinct E-prostanoid (EP) receptor isoforms: EP1-EP4. The EP4 receptor (EP4R) triggers macula densa stimulation of renin, induces vasodilation, and may inhibit epithelial sodium transport. Thus, the impact of EP4Rs on BP may differ with the sites of PGE2 synthesis and pattern of EP4R activation within the kidney. To examine the role of EP4R on BP regulation we generated EP4R-deficient mice. Because deletion of EP4R in utero causes peri-natal mortality due to persistent patent ductus arteriosus, we carried out conditional deletion by crossing EP4flox/flox with a transgenic line with tamoxifen-inducible Cre expression in all tissues. Resting mean arterial pressure (MAP) measured by radiotelemetry was increased by 5±1mm Hg (p<0.05) in mice with total-body EP4R-deficiency (EP4R-TBKO) vs. controls. In addition, EP4R-TBKOs had an exaggerated increase in MAP with high-salt (6% NaCl) feeding (MAP increase: 5±1 vs. 2±1mmHg for controls; p<0.05) and during angiotensin II (Ang II)-dependent hypertension (MAP increase: 37±2 vs. 24±3mmHg for controls; p<0.05). We next hypothesized that exaggerated hypertension in the EP4R-TBKOs was due to elimination of compensatory EP4R-depedent vasodilation mediated by direct actions in vascular smooth muscle cells (VSMCs). Accordingly, we generated mice lacking EP4R in VSMCs (EP4R-SMKOs) using EP4flox/flox and transgenic mice with tamoxifen-inducible expression of Cre limited to smooth muscle cells. In contrast to the EP4R-TBKOs, elimination of EP4R only from VSMC reduced resting MAP by 5±1mm Hg (p<0.04) but did not affect the BP response to high salt feeding (MAP change: 2±1 vs. 2±1 mm Hg; ns) or chronic Ang II infusion (MAP increase: 29±3 vs. 34±4 mm Hg; ns). Thus, the EP4R modulates resting MAP but its specific impact may vary between EP4R populations in different cell lineages. EP4Rs resist the development of salt- and Ang II-dependent hypertension. These anti-hypertensive actions are not mediated by direct effects of EP4R in VSMCs, but may involve EP4R in endothelium, brain, or kidney epithelia.

Phosphodiesterase 4 Inhibitor Roflumilast Improves the Bronchodilative Effect of Sevoflurane in Sensitized Airways

2014 ◽  
Vol 120 (5) ◽  
pp. 1152-1159 ◽  
Author(s):  
Jing Zhou ◽  
Sohshi Iwasaki ◽  
Michiaki Yamakage
Keyword(s):  
Smooth Muscle ◽  
Volatile Anesthetic ◽  
Cyclic Adenosine Monophosphate ◽  
Relaxation Effect ◽  
Adenosine Monophosphate ◽  
Bronchodilator Effect ◽  
Phosphodiesterase 4 ◽  
Phosphodiesterase 4 Inhibitors ◽  
Lung Resistance ◽  
Total Lung Resistance

Abstract Background: Although phosphodiesterase 4 inhibitors and the volatile anesthetic sevoflurane are known to have independent bronchodilator properties, the combined administration of these two agents may have the potential to exert an additive or synergistic bronchodilator effect. The authors tested this hypothesis and investigated the common site of this combined relaxation effect in a model of airway hyperresponsiveness with ovalbumin-sensitized guinea pigs. Methods: Ovalbumin-sensitized animals (n = 138) were randomized into six groups: sensitized, sevoflurane, rolipram1.0, roflumilast1.0, sevoflurane/rolipram1.0, and sevoflurane/roflumilast1.0. Total lung resistance in vivo, airway smooth muscle tension in vitro, and intracellular cyclic adenosine monophosphate levels were measured to evaluate the relaxation effect. Results: Among the six sensitized groups, total lung resistance was higher in the order of sensitized &gt; sevoflurane &gt; rolipram 1.0 &gt; roflumilast1.0 &gt; sevoflurane/rolipram1.0 &gt; sevoflurane/roflumilast1.0, with an increase in acetylcholine concentration. Compared with the other five groups, the muscle tensions in the sevoflurane/roflumilast1.0 group were significantly lower at carbacholine doses of 10−7, 10−6, and 10−5 M; the cyclic adenosine monophosphate concentrations (means ± SD) in the sevoflurane/rolipram1.0 (1.61 ± 0.34) and sevoflurane/roflumilast1.0 (1.50 ± 0.20) groups were higher than that in the sensitized (0.52 ± 0.15) and sevoflurane (1.12 ± 0.32) groups. Conclusions: The combined use of phosphodiesterase 4 inhibitors with the volatile anesthetic sevoflurane had an additive bronchodilator effect in ovalbumin-sensitized guinea pigs. The concurrent increase in cyclic adenosine monophosphate levels in sensitized airway smooth muscle might be a mechanism of this combined relaxation effect.

Sympathoadrenal mechanisms in hemodynamic responses to gastric distension in cats

1982 ◽  
Vol 243 (5) ◽  
pp. H748-H753 ◽  
Author(s):  
J. C. Longhurst ◽  
J. Ibarra
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Adrenergic Receptor ◽  
Contractile Response ◽  
Bilateral Adrenalectomy ◽  
Gastric Distension ◽  
Adrenergic Blockade ◽  
Receptor Stimulation

There is presently little information on the efferent mechanisms responsible for the reflex cardiovascular activation during passive gastric distension. Therefore, 40 cats anesthetized with alpha-chloralose were studied with passive gastric balloon distention before and during 1) two repeated gastric distensions, 2) beta-adrenergic blockade with propranolol, 3) alpha-adrenergic blockade with phentolamine, or 4) bilateral adrenalectomy. Before and during each distension mean arterial pressure, heart rate, cardiac output, rate of rise of left ventricular pressure (dP/dt) at 40 mmHg developed pressure and calculated systemic vascular resistance were determined. Repeated gastric distension caused similar hemodynamic responses without tachyphylaxis. beta-Blockade significantly reduced the increase in dP/dt from 893 +/- 362 to 150 +/- 63 mmHg/s. alpha-Blockade significantly altered the changes in mean arterial pressure from 33 +/- 5.0 to -2 +/- 4.7 mmHg and systemic vascular resistance from 0.114 +/- 0.019 to 0.004 +/- 0.031 peripheral resistance units. Bilateral adrenalectomy significantly diminished the contractile response from 525 +/- 107 to 50 +/- 85 mmHg/s but did not significantly alter the pressor and vasoconstrictor responses. We conclude that, during passive gastric distension in cats, the increase in myocardial contractility is mediated by beta-adrenergic-receptor stimulation, whereas the arterial vasoconstrictor and pressor responses are mediated by alpha-adrenergic receptor stimulation. Additionally, during gastric distension a substantial portion of the contractile response is dependent on the integrity of the adrenal glands.

scholarly journals Brain Prostaglandin D2 Increases Neurogenic Pressor Activity and Mean Arterial Pressure in Angiotensin II-Salt Hypertensive Rats

Hypertension ◽  
2019 ◽  
Vol 74 (6) ◽  
pp. 1499-1506 ◽  
Author(s):  
Ninitha Asirvatham-Jeyaraj ◽  
A. Daniel Jones ◽  
Robert Burnett ◽  
Gregory D. Fink
Keyword(s):  
Cerebrospinal Fluid ◽  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Developmental Stage ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Salt Hypertension ◽  
Pressor Activity

This study tested whether brain L-PGDS (lipocalin-type prostaglandin [PG] D synthase), through prostanoid signaling, might increase neurogenic pressor activity and thereby cause hypertension. Sprague Dawley rats on high-salt diet received either vehicle or Ang II (angiotensin II) infusion. On day 4, the developmental stage of hypertension, brains from different sets of control and Ang II–treated rats were collected for measuring L-PGDS expression, PGD2 levels, and DP1R (type 1 PGD2 receptor) expression. In a different set of 14-day Ang II-salt–treated rats, mini-osmotic pumps were used to infuse either a nonselective COX (cyclooxygenase) inhibitor ketorolac, L-PGDS inhibitor AT56, or DP1R inhibitor BWA868C to test the role of brain COX-PGD2-DP1R signaling in Ang II-salt hypertension. The acute depressor response to ganglion blockade with hexamethonium was used to quantify neurogenic pressor activity. During the developmental stage of Ang II-salt hypertension, L-PGDS expression was higher in cerebrospinal fluid, and PGD2 levels were increased in the choroid plexus, cerebrospinal fluid, and the cardioregulatory brain region rostral ventrolateral medulla. DP1R expression was decreased in rostral ventrolateral medulla. Both brain COX inhibition with ketorolac and L-PGDS inhibition with AT56 lowered mean arterial pressure by altering neurogenic pressor activity compared with vehicle controls. Blockade of DP1R with BWA868C, however, increased the magnitude of Ang II-salt hypertension and significantly increased neurogenic pressor activity. In summary, we establish that the development of Ang II-salt hypertension requires increased COX- and L-PGDS–derived PGD2 production in the brain, making L-PGDS a possible target for treating neurogenic hypertension.

Sign in / Sign up

Export Citation Format

Share Document