Thromboxane A2 mimetic U-46619 induces systemic and pulmonary hypertension and delayed tachypnea in the goat

1994 ◽  
Vol 77 (3) ◽  
pp. 1466-1473 ◽  
Author(s):  
J. A. Carrithers ◽  
D. Brown ◽  
F. Liu ◽  
J. A. Orr
Keyword(s):  
Sodium Nitroprusside ◽  
Pressor Response ◽  
Thromboxane A2 ◽  
Relative Increase ◽  
Breathing Frequency ◽  
Systemic Arterial Hypertension ◽  
Arterial Blood ◽  
Before And After ◽  
Pulmonary Arterial ◽  
Stimulation Of

Cardiorespiratory variables were measured continuously in five conscious goats before and after the infusion of U-46619 at a dose of either 2, 4, or 6 micrograms.kg-1.5 min-1. Infusion of U-46619 led to immediate increases in pulmonary arterial blood pressure (ABP) that were sustained for up to 15 min after the end of the infusion. Systemic ABP also increased, but the relative increase from control was less than the pulmonary pressor response. At the highest dose, U-46619 elicited a delayed tachypneic response that was greatest several minutes after the infusion was stopped. U-46619 was also infused simultaneously with sodium nitroprusside to clamp ABP pressure at baseline levels to determine whether stimulation of baroreceptors might contribute to the latency of the tachypneic response. Although sodium nitroprusside infusion prevented the increase in ABP, the increase in breathing frequency was still delayed 3–4 min from the start of the infusion. We conclude that U-46619 elicits pulmonary and systemic arterial hypertension in the conscious goat. At the higher dose U-46619 also elicits a delayed tachypnea that remains delayed even if ABP is normal.

Pulmonary pressor response after prostaglandin synthesis inhibition in conscious dogs

1982 ◽  
Vol 52 (3) ◽  
pp. 705-709 ◽  
Author(s):  
B. R. Walker ◽  
N. F. Voelkel ◽  
J. T. Reeves
Keyword(s):  
Cardiac Output ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Pressor Response ◽  
Conscious Dogs ◽  
Pulmonary Pressure ◽  
Time Control ◽  
Mean Pulmonary Arterial Pressure ◽  
Before And After ◽  
Pulmonary Arterial

Recent studies have shown that vasodilator prostaglandins are continually produced by the isolated rat lung. We postulated that these vasodilators may contribute to maintenance of normal low pulmonary arterial pressure. Pulmonary pressure and cardiac output were measured in conscious dogs prior to and 30 to 60 min following administration of meclofenamate (2 mg/kg iv, followed by infusion at 2 mg . kg-1 . h-1) or the structurally dissimilar inhibitor RO–20–5720 (1 mg/kg iv, followed by infusion at 1 mg . kg-1 . h-1). The animals were also made hypoxic with inhalation of 10% O2 before and after inhibition. Time-control experiments were conducted in which only the saline vehicle was administered. Meclofenamate or RO–20–5720 caused an increase in mean pulmonary arterial pressure and total pulmonary resistance. Cardiac output and systemic pressure were unaffected. The mild hypoxic pulmonary pressor response observed was not affected by meclofenamate. Animals breathing 30% O2 to offset Denver's altitude also demonstrated increased pulmonary pressure and resistance when given meclofenamate. It is concluded that endogenous vasodilator prostaglandins may contribute to normal, low vascular tone in the pulmonary circulation.

A role for NMDA receptors in posthypoxic frequency decline in the rat

1998 ◽  
Vol 274 (6) ◽  
pp. R1546-R1555 ◽  
Author(s):  
Sharon K. Coles ◽  
Paul Ernsberger ◽  
Thomas E. Dick
Keyword(s):  
Nmda Receptors ◽  
Receptor Activation ◽  
Respiratory Pattern ◽  
Breathing Frequency ◽  
Respiratory Response ◽  
Arterial Blood ◽  
Before And After ◽  
High Doses ◽  
The Brain ◽  
Nmda Receptor Activation

Posthypoxic frequency decline (PHFD) refers to the undershoot in respiratory frequency that follows brief hypoxic exposures. Lateral pontine neurons are required for PHFD. The neurotransmitters involved in the circuit that activate and/or are released by these pontine neurons regulating PHFD are unknown. We hypothesized that N-methyl-d-aspartate (NMDA) receptors are required for PHFD, because of the similarity in respiratory pattern after blocking lateral pontine activity or NMDA receptors. Furthermore, we hypothesized that the location of these NMDA receptors could be visualized by optimizing binding affinity with spermidine. In vagotomized, anesthetized rats ( n = 16), cardiorespiratory responses to hypoxia (8% O2, 30–90 s) were recorded before and after dizocilpine (10 μg-1 mg/kg iv), and NMDA receptors were mapped with [3H]dizocilpine ( n = 6). Dizocilpine elicited a dose-related effect on PHFD, blocking PHFD at high doses. Resting arterial blood pressure and breathing frequency decreased with high doses of dizocilpine, but the respiratory response to hypoxia remained intact. Our novel anatomical data indicate that NMDA receptors were widespread but distributed differentially in the brain stem. We conclude that NMDA receptors are located in pontine and medullary respiratory-related regions and that PHFD requires NMDA-receptor activation.

Potentiation of hypoxic pulmonary vasoconstriction by ethyl alcohol in dogs

1978 ◽  
Vol 44 (1) ◽  
pp. 76-80 ◽  
Author(s):  
R. C. Doekel ◽  
E. K. Weir ◽  
R. Looga ◽  
R. F. Grover ◽  
J. T. Reeves
Keyword(s):  
Pressor Response ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Blood Gases ◽  
Adrenergic Blockade ◽  
Mechanically Ventilated ◽  
Pulmonary Vasoconstriction ◽  
Arterial Blood ◽  
Before And After ◽  
Pressor Activity ◽  
Inhibition Of Prostaglandin Synthesis

Pulmonary and systemic hemodynamics and arterial blood gases were measured in anesthetized and mechanically ventilated dogs before and after oral or intravenous administration of ethanol. Increases in mean pulmonary artery pressure and pulmonary vascular resistance occurred. Platelet antiserum-induced thrombocytopenia inhibition of prostaglandin synthesis with meclofenamate, or alpha-adrenergic blockade did not alter the pulmonary pressor response to ethanol. However, the increase in resistance following ethanol was abolished by hyperoxia and potentiated by hypoxia. Thus, it appears that the effect of ethanol is to augment hypoxic pulmonary vasoconstriction, whereas ethanol per se has no independent pulmonary pressor activity.

CO2-sensitive olfactory and pulmonary receptor modulation of episodic breathing in bullfrogs

1996 ◽  
Vol 270 (1) ◽  
pp. R134-R144 ◽  
Author(s):  
R. Kinkead ◽  
W. Milsom
Keyword(s):  
Breathing Pattern ◽  
Olfactory Receptors ◽  
Breathing Frequency ◽  
Receptor Modulation ◽  
Arterial Blood ◽  
Pulmonary Receptor ◽  
Sudden Release ◽  
Kinetics Of ◽  
Tonic Stimulation ◽  
Stimulation Of

Breathing was monitored during normocarbia, hypercarbia (6% CO2 in air), and the period immediately after the return to normocarbic conditions in intact, olfactory-denervated, and vagotomized bullfrogs. In intact frogs, ventilation increased during hypercarbia, but the breathing pattern remained episodic. Immediately upon return to air, there was a further paradoxical increase in breathing frequency, and breathing became continuous in most frogs. Results obtained from animals after olfactory receptor denervation indicate that tonic stimulation of olfactory receptors by airway CO2 inhibited breathing during hypercarbia. Measurements of the kinetics of changes in airway and arterial blood CO2 levels support the suggestion that the sudden release of this inhibition on the return to normocarbic conditions was responsible for the posthypercarbic hyperpnea. Vagotomy increased ventilation during normocarbia. Hypercarbia now caused a change in breathing pattern but had no net effect on total ventilation, suggesting that pulmonary vagal feedback inhibited ventilation during normocarbia but stimulated ventilation during hypercarbia. Although olfactory and pulmonary receptor feed-back shape the breathing pattern, they were not responsible for initiating or terminating the episodes of breathing.

Attenuated arterial baroreflex buffering of muscle metaboreflex in heart failure

2005 ◽  
Vol 289 (6) ◽  
pp. H2416-H2423 ◽  
Author(s):  
Jong-Kyung Kim ◽  
Javier A. Sala-Mercado ◽  
Robert L. Hammond ◽  
Jaime Rodriguez ◽  
Tadeusz J. Scislo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pressor Response ◽  
Dynamic Exercise ◽  
Arterial Baroreflex ◽  
Muscle Metaboreflex ◽  
Peripheral Vasoconstriction ◽  
Arterial Blood ◽  
Pressor Responses ◽  
Before And After ◽  
Chronically Instrumented Dogs

Previous studies have shown that heart failure (HF) or sinoaortic denervation (SAD) alters the strength and mechanisms of the muscle metaboreflex during dynamic exercise. However, it is still unknown to what extent SAD may modify the muscle metaboreflex in HF. Therefore, we quantified the contribution of cardiac output (CO) and peripheral vasoconstriction to metaboreflex-mediated increases in mean arterial blood pressure (MAP) in conscious, chronically instrumented dogs before and after induction of HF in both barointact and SAD conditions during mild and moderate exercise. The muscle metaboreflex was activated via partial reductions in hindlimb blood flow. After SAD, the metaboreflex pressor responses were significantly higher with respect to the barointact condition despite lower CO responses. The pressor response was significantly lower in HF after SAD but still higher than that of HF in the barointact condition. During control experiments in the barointact condition, total vascular conductance summed from all beds except the hindlimbs did not change with muscle metaboreflex activation, whereas in the SAD condition both before and after induction of HF significant vasoconstriction occurred. We conclude that SAD substantially increased the contribution of peripheral vasoconstriction to metaboreflex-induced increases in MAP, whereas in HF SAD did not markedly alter the patterns of the reflex responses, likely reflecting that in HF the ability of the arterial baroreflex to buffer metaboreflex responses is impaired.

α1-Adrenoceptor Blockade: Dissociation of Its Effects on Renin Release and Arterial Blood Pressure in Man

1981 ◽  
Vol 61 (s7) ◽  
pp. 307s-309s ◽  
Author(s):  
A. Morganti ◽  
Carla Sala ◽  
Anna Palermo ◽  
Lucia Turolo ◽  
A. Zanchetti
Keyword(s):  
Arterial Pressure ◽  
Plasma Renin Activity ◽  
Pressor Response ◽  
Plasma Renin ◽  
Test Dose ◽  
Blocking Agent ◽  
Renin Activity ◽  
Renin Release ◽  
Arterial Blood ◽  
Before And After

1. The possibility that the juxtaglomerular α1-adrenoceptors mediate an inhibitory action on renin release in man was examined in seven patients with essential hypertension, by measuring (i) the acute effects of prazosin (0.25 mg intravenously), a selective α1-adrenoceptor-blocking agent, on arterial pressure and plasma renin activity, the degree of α-blockade induced by the drug being assessed by comparing the pressor response with that to a test dose of phenylephrine before and after prazosin administration, and (ii) the increases in plasma renin activity in response to isoprenaline before and during the prazosin-induced α-blockade. 2. Twenty minutes after the infusion of prazosin, when the pressor response to phenylephrine was reduced by 80% with respect to control, (i) mean arterial pressure was practically unchanged, (ii) plasma renin activity was almost doubled and (iii) the increases in plasma renin activity in response to isoprenaline were significantly greater, both in absolute and percentage values, than those observed before prazosin. 3. The increments in baseline plasma renin activity induced by prazosin in the absence of decrease in arterial pressure and the enhancement in renin responsiveness to the β-adrenoceptor stimulus suggest that, in man, the juxtaglomerular α1-adrenoceptors exert a direct, suppressive action on renin release.

Pressor response from rostral dorsomedial medulla is mediated by excitatory amino acid receptors in rostral VLM

1994 ◽  
Vol 267 (1) ◽  
pp. R309-R315 ◽  
Author(s):  
Y. Hirooka ◽  
J. W. Polson ◽  
R. A. Dampney
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Pressor Response ◽  
Ventrolateral Medulla ◽  
Amino Acid Receptors ◽  
Control Value ◽  
Afferent Fibers ◽  
Pressor Responses ◽  
Before And After ◽  
Stimulation Of

Excitatory amino acid (EAA) receptors in the rostral part of the ventrolateral medulla (VLM) have been shown to mediate pressor responses elicited by stimulation of various peripheral afferent fibers as well as other central nuclei. This study tested the hypothesis that these receptors are a critical component in the central pathway mediating the powerful pressor response that is produced by stimulation of a group of neurons within a circumscribed region in the rostral dorsomedial medulla (RDM). In anesthetized rabbits, the pressor response elicited by unilateral microinjection of glutamate into this RDM region was measured before and after injection of kynurenic acid (Kyn), a broad-spectrum EAA receptor antagonist, into the physiologically identified pressor region of either the ipsilateral or contralateral rostral VLM. The pressor response to RDM stimulation was greatly reduced (to 24 +/- 4% of control) 5-10 min after injection of Kyn (but not the vehicle solution) into the ipsilateral rostral VLM; this response returned completely to its control value within 30-60 min after Kyn injection. By contrast, after Kyn injection into the contralateral rostral VLM, the pressor response to RDM stimulation was not affected (106 +/- 15% of control). The results indicate that the descending pressor pathway from the RDM to the spinal cord is mediated by EAA receptors in the rostral VLM pressor region. Furthermore, the pathway from the RDM to the rostral VLM is predominantly, if not exclusively, ipsilateral.

Attenuated pulmonary pressor response to hypoxia in bar-headed geese

1984 ◽  
Vol 247 (2) ◽  
pp. R402-R403 ◽  
Author(s):  
F. M. Faraci ◽  
D. L. Kilgore ◽  
M. R. Fedde
Keyword(s):  
Blood Pressure ◽  
Pressor Response ◽  
Control Mechanisms ◽  
Vascular Control ◽  
Pekin Ducks ◽  
Arterial Blood ◽  
O2 Partial Pressure ◽  
Unique Model ◽  
Pulmonary Arterial ◽  
Anser Indicus

We determined the pulmonary pressor response during hypoxia in bar-headed geese (Anser indicus), a species that flies at altitudes up to 9,000 m, and Pekin ducks (Anas platyrhynchos), a non-flyer. Mean pulmonary arterial blood pressure (PAP) and arterial O2 partial pressure (PaO2) were measured in unanesthetized birds acutely exposed to 21, 10, 5, and, in geese only, 4% O2. PAP in geese did not change as PaO2 was reduced from 95 to 46 Torr and rose only 3 mmHg when PaO2 was reduced to 28 Torr. The same PaO2 decline in ducks (99 to 29 Torr) resulted in an 11-mmHg rise in PAP. The data suggest that very little or no increase in pulmonary vascular resistance occurs in these geese during hypoxia. This bird may provide a unique model in which to study pulmonary vascular control mechanisms.

Ventilatory effects of stimulation of phrenic afferents

1987 ◽  
Vol 63 (3) ◽  
pp. 1063-1069 ◽  
Author(s):  
J. D. Road ◽  
N. H. West ◽  
B. N. Van Vliet
Keyword(s):  
Blood Pressure ◽  
Pressor Response ◽  
Sensory Innervation ◽  
Respiratory Muscle Fatigue ◽  
Pentobarbital Sodium ◽  
Arterial Blood ◽  
Afferent Activation ◽  
Ventilatory Drive ◽  
Alpha Chloralose ◽  
Stimulation Of

The diaphragm, a ventilatory muscle, has abundant sensory innervation. The effects of phrenic afferent activation on ventilation have been varied. In this study the proximal end of the phrenic nerve was electrically stimulated, and the effects on ventilation were measured in supine dogs anesthetized with either alpha-chloralose or pentobarbital sodium. We found a maximum increase in ventilation of 45 +/- 4% in the alpha-chloralose group and an increase in mean arterial blood pressure of 18 +/- 4%. This response was obtained at high stimulus intensities (60 times twitch threshold). Stimulation of the proximal end of the gastrocnemius nerve produced a similar ventilatory response (61 +/- 10%) but at lower stimulus intensities. During pentobarbital sodium anesthesia both the hyperventilation and the pressor response were produced; however, ventilation was increased by an increase in respiratory frequency. The reflex was abolished by sectioning of the cervical dorsal roots (C4-C7). Proximal cold blockade of the nerve abolished the response at a perineural temperature of 1.35 +/- 0.64 degrees C. The main effect of activation of phrenic afferents was an increase in ventilation and blood pressure that was mediated by unmyelinated fibers and possibly thin myelinated fibers. This response is similar to skeletal muscle afferent activation and may play a role in ventilatory drive during such conditions as exercise and respiratory muscle fatigue.

Stiffened erythrocytes augment the pulmonary hemodynamic response to hypoxia

1990 ◽  
Vol 69 (4) ◽  
pp. 1270-1275 ◽  
Author(s):  
M. P. Doyle ◽  
B. R. Walker
Keyword(s):  
Pressor Response ◽  
Acute Hypoxia ◽  
Hemodynamic Response ◽  
Flow Rates ◽  
Arterial Blood ◽  
Pulmonary Hemodynamic ◽  
Pulmonary Arterial ◽  
Phosphate Buffered Saline ◽  
Filtration Technique ◽  
Rbc Deformability

Isolated rat lungs were perfused with suspensions containing normal and stiffened erythrocytes (RBCs) during normoxic and hypoxic ventilation to assess the effect of reduced RBC deformability on the hypoxic pressor response. RBC suspensions were prepared with cells previously incubated in isotonic phosphate-buffered saline with or without 0.0125% glutaraldehyde. The washed RBCs were resuspended in isotonic bicarbonate-buffered saline (with 4% albumin) to hematocrits of approximately 35%. The lungs were perfused with control and experimental cell suspensions in succession while pulmonary arterial pressure was measured during normoxic (21% O2) and hypoxic (3% O2) ventilation. On the attainment of a peak hypoxic pressor response, flow rate was changed so that pressure-flow curves could be constructed for each suspension. RBC deformability was quantified by a filtration technique using 4.7-microns-pore filters. Glutaraldehyde treatment produced a 10% decrease in RBC deformability (P less than 0.05). Over the range of flow rates, Ppa was increased by 15-17% (P less than 0.05) and 26-31% (P less than 0.05) during normoxic and hypoxic ventilation, respectively, when stiffened cells were suspended in the perfusate. The magnitude of the hypoxic pressor response was 50-54% greater with stiffened cells over the three flow rates. In a separate set of experiments, normoxic and hypoxic arterial blood samples from conscious unrestrained rats were used to investigate the effects of acute hypoxia on RBC deformability. Deformability was measured with the same filtration technique. There was no difference in the deformability of hypoxic compared with normoxic RBCs. We conclude that the presence of stiffened RBCs enhances the hemodynamic response to hypoxia but acute hypoxia does not affect RBC deformability.

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