Developmental changes in respiratory, febrile, and cardiovascular responses to PGE2 in newborn lambs

2000 ◽  
Vol 278 (6) ◽  
pp. R1460-R1473 ◽  
Author(s):  
T. C. Tai ◽  
S. L. Adamson

PGE2 has centrally mediated respiratory, febrile, and cardiovascular effects that markedly differ between fetal and adult life. We hypothesized that the transition from fetal to adult responses to PGE2 occurs in the newborn period. Thus effects of an intracarotid infusion of PGE2 (3 μg/min for 60 min) were determined in unanesthetized newborn lambs at 5, 10, and 15 days after birth. At 5 days, PGE2 reduced central CO2 sensitivity, reduced lung ventilation due to a decrease in breathing frequency, and induced hypercapnia. By 15 days, these effects of PGE2 had waned significantly. In contrast, phasic (expiratory) thyroarytenoid muscle electromyogram activity, number of short apneas, and incidence of Biot periodic breathing were similarly increased at all three ages. PGE2 induced a sustained fever at 10 and 15 days. Heart rate and mean arterial blood pressure were unchanged in contrast to marked increases observed by others in adults. Results showed that the transition from fetal to adult respiratory and febrile responses to PGE2 occurs in early postnatal life, whereas adult cardiovascular responses develop later in life in sheep.

1999 ◽  
Vol 277 (4) ◽  
pp. H1385-H1391 ◽  
Author(s):  
Sarah M. Wells ◽  
B. Lowell Langille ◽  
J. Michael Lee ◽  
S. Lee Adamson

We previously reported changes in mechanical properties and collagen cross-linking of the ovine thoracic aorta during perinatal development and postnatal maturation, and we now report changes in biochemical composition (elastin, collagen, and DNA contents per mg wet wt) over the same developmental intervals. A comparison of results from the present and previous studies has yielded novel and important observations concerning the relationship between aortic mechanics and composition during maturation. Developmental changes in aortic incremental elastic modulus at low tensile stress ( E low) closely followed changes in relative elastin content (i.e., per mg wet wt). An 89% increase in E low during the perinatal period was associated with a 69% increase in relative elastin content, whereas neither variable changed during postnatal life. Incremental elastic modulus at high tensile stress ( E high) did not change during the perinatal period but increased 88% during postnatal life. This pattern closely paralleled changes in collagen cross-linking index, which did not change perinatally but almost doubled postnatally. In contrast, relative collagen content (per mg wet wt) increased only slightly from fetal to adult life, a trend that was unrelated to aortic mechanics. Substantial, progressive decreases in measures of wall viscosity (pressure wave attenuation coefficient and viscoelastic phase angle) from fetal to adult life followed the pattern observed for relative DNA (smooth muscle cell) content (per mg wet wt). Our findings suggest that accumulation of elastin per milligram wet weight contributes most to developmental changes in E low, change in collagen cross-linking is the primary determinant of developmental changes in E high, and cell accumulation contributes most to developmental changes in wall viscosity.


2003 ◽  
Vol 95 (3) ◽  
pp. 1159-1169 ◽  
Author(s):  
Joshua R. Rodman ◽  
Kathleen S. Henderson ◽  
Curtis A. Smith ◽  
Jerome A. Dempsey

In awake dogs, lactic acid was injected into the phrenic and deep circumflex iliac arteries to elicit the diaphragm and abdominal muscle metaboreflexes, respectively. At rest, injections into the phrenic or deep circumflex iliac arteries significantly increased mean arterial blood pressure 21 ± 7% and reduced cardiac output 6 ± 2% and blood flow to the hindlimbs 20 ± 9%. Simultaneously, total systemic, hindlimb, and abdominal expiratory muscle vascular conductances were reduced. These cardiovascular responses were not accompanied by significant changes in the amplitude or timing of the diaphragm electromyogram. During treadmill exercise that increased cardiac output, hindlimb blood flow, and vascular conductance 159 ± 106, 276 ± 309, and 299 ± 90% above resting values, lactic acid injected into the phrenic or deep circumflex iliac arteries also elicited pressor responses and reduced hindlimb blood flow and vascular conductance. Adrenergic receptor blockade at rest eliminated the cardiovascular effects of the respiratory muscle metaboreflex. We conclude that the cardiovascular effects of respiratory muscle metaboreflex activation are similar to those previously reported for limb muscles. When activated via metabolite production, the respiratory muscle metaboreflex may contribute to the increased sympathetic tone and redistribution of blood flow during exercise.


1995 ◽  
Vol 269 (1) ◽  
pp. H135-H139 ◽  
Author(s):  
Y. Seki ◽  
Y. Suzuki ◽  
M. K. Baskaya ◽  
K. Saito ◽  
M. Takayasu ◽  
...  

The cardiovascular responses to intracisternally administered pituitary adenylate cyclase-activating polypeptide (PACAP) were investigated and compared with those of vasoactive intestinal peptide (VIP) in anesthetized dogs. Intracisternal administration of 10 nmol of PACAP-27 increased mean arterial blood pressure (MABP) significantly with a simultaneous increase of plasma arginine vasopressin and epinephrine concentrations. Intracisternal administration of VIP increased plasma arginine vasopressin concentration significantly but caused no appreciable change in MABP. Systemic infusion of the nonpeptide vasopressin V1 receptor antagonist OPC-21268 did not inhibit the PACAP-27-induced increase in MABP, whereas phentolamine, an alpha-adrenoceptor blocker, reversed the increase. Intracisternal pretreatment with the vasopressin V1 receptor antagonist [Pmp1, Tyr(Me)2]Arg8-vasopressin also inhibited the increase. These findings suggest that PACAP has a central pressor action by increasing sympathetic outflow, which is probably mediated by the vasopressinergic neural network. PACAP seems to play important roles in hormonal and neural control of systemic circulation.


2000 ◽  
Vol 89 (3) ◽  
pp. 947-955 ◽  
Author(s):  
Giuseppe Insalaco ◽  
Salvatore Romano ◽  
Adriana Salvaggio ◽  
Alberto Braghiroli ◽  
Paola Lanfranchi ◽  
...  

The ventilatory and arterial blood pressure (ABP) responses to isocapnic hypoxia during wakefulness progressively increased in normal subjects staying 4 wk at 5,050 m (Insalaco G, Romano S, Salvaggio A, Braghiroli A, Lanfranchi P, Patruno V, Donner CF, and Bonsignore G; J Appl Physiol 80: 1724–1730, 1996). In the same subjects ( n = 5, age 28–34 yr) and expedition, nocturnal polysomnography with ABP and heart rate (HR) recordings were obtained during the 1st and 4th week to study the cardiovascular effects of phasic (i.e., periodic breathing-dependent) vs. tonic (i.e., acclimatization-dependent) hypoxia during sleep. Both ABP and HR fluctuated during non-rapid eye movement sleep periodic breathing. None of the subjects exhibited an ABP increase during the ventilatory phases that correlated with the lowest arterial oxygen saturation of the preceding pauses. Despite attenuation of hypoxemia, ABP and HR behaviors during sleep in the 4th wk were similar to those in the 1st wk. Because ABP during periodic breathing in the ventilatory phase increased similarly to the ABP response to progressive hypoxia during wakefulness, ABP variations during ventilatory phases may reflect ABP responsiveness to peripheral chemoreflex sensitivity rather than the absolute value of hypoxemia, suggesting a major tonic effect of hypoxia on cardiorespiratory control at high altitude.


1993 ◽  
Vol 71 (7) ◽  
pp. 453-464 ◽  
Author(s):  
Haroutioun Hasséssian ◽  
Philippe Poulat ◽  
Edith Hamel ◽  
Tomás A. Reader ◽  
Réjean Couture

The aim of this study was to characterize, in conscious rats, the spinal cord 5-hydroxytryptamine (5-HT) receptors involved in mean arterial pressure (MAP) and heart rate (HR) regulation as well as to examine the influence of bulbospinal 5-HT fibers on cardiovascular responses to intrathecal (i.t.) substance P (SP). The i.t. injection of 5-HT or 5-carboxamidotryptamine (5-CT) (5-HT1A, 1B, 1D agonist) reduced MAP and increased HR in a dose-dependent manner. In contrast, the agonists 8-hydroxy-2-(di-n-propylamino)tetraiin (8-OH-DPAT, 5-HT1A agonist) and α-CH3-5-HT (5-HT1C and 5-HT2) only caused a decrease in HR, while the agonist 2-CH3-5-HT (5-HT3) was devoid of cardiovascular effects. The vasodepressor response to 5-CT was antagonized by methiothepin but not affected by mesulergine, ketanserin, propranolol, or yohimbine. However, all five antagonists reduced the HR increase to 5-CT. Ketanserin, propranolol, mesulergine, yohimbine, and methysergide were without effect on resting MAP, while methiothepin reduced MAP. Methiothepin, ketanserin, and methysergide increased resting HR, yet the other antagonists had no effect on this parameter. Rats treated with p-chlorophenylalanine or 5,7-dihydroxytryptamine, but not with 6-hydroxydopamine, exhibited higher resting HR than that of control rats. Although the resting MAP was unaffected, the pressor response to i.t. SP was significantly enhanced by either 5-HT toxin. The results suggest that the receptor mediating the depressor response to 5-HT and 5-CT conforms with the broad pharmacological profile of a 5-HT1-like receptor and is unlikely to be of the 5-HT2 or 5-HT3 subtype. Since the HR response evoked by 5-CT was blocked by antagonists that exhibit affinities for various 5-HT receptor subtypes, it is suggested that a nonspecific blockade or, alternatively, that more than one receptor contributes to this cardiac effect. In addition, the results raise the possibility that a spinal 5-HT input, likely mediated by 5-HT2 receptors, tonically inhibits HR. Hence, an antagonistic interaction between 5-HT and SP is proposed to play a role in the control of arterial blood pressure in the spinal cord.Key words: 5-hydroxytryptamine, 5-HT receptors, substance P, spinal cord, cardiovascular regulation.


1992 ◽  
Vol 70 (12) ◽  
pp. 2303-2310 ◽  
Author(s):  
Richard Stephenson ◽  
Michael S. Hedrick ◽  
David R. Jones

Cardiovascular responses during diving behaviour were recorded via a cannulated carotid artery in five rhinoceros auklets. Heart rate and mean arterial blood pressure were unchanged from predive values during both escape and feeding dives. The responses to feeding dives and escape dives did not differ. Acidosis, accompanying elevated steady-state plasma lactate levels during escape diving activity, was partially compensated by lung ventilation between dives. The absence of progressive accumulation of lactate in the blood implies that an aerobic steady state was attained, despite the short intervals between dives (2.4 ± 0.4 s). Arterial blood oxygen tension was maintained at reduced levels (50–60 mmHg; 1 mmHg = 133.322 Pa) for up to 32 min of continuous escape diving activity. Immersion of restrained auklets or capture of diving auklets in a net provoked a rapid and intense bradycardia. Growth of hand-reared auklet nestlings peaked at a time corresponding to the natural fledging age for this species but the urge to leave the nest box was not triggered by reduced food availability, as has been suggested for wild semi-precocial alcids. Potential pitfalls in the maintenance and use of alcids in physiological research are discussed.


1987 ◽  
Vol 252 (1) ◽  
pp. R127-R133 ◽  
Author(s):  
B. R. Walker

Experiments were performed to test the possible involvement of arginine vasopressin (AVP) in the systemic cardiovascular responses to acute hypercapnic acidosis in conscious chronically instrumented rats. Exposure to 6% CO2 caused arterial PCO2 to rise from 34 +/- 2 to 53 +/- 1 Torr. This level of hypercapnia was associated with a consistent bradycardia; however, cardiac output, blood pressure, and total peripheral resistance were not significantly affected. Administration of 10 micrograms/kg iv of the specific V1 vasopressinergic antagonist d(CH2)5Tyr(Me)AVP during 6% CO2 had no effect on any of the measured hemodynamic variables. Furthermore, d(CH2)5Tyr(Me)AVP also had no effect in normocapnic control animals. Exposure to a more severe level of hypercapnia (10% CO2, arterial PCO2 = 89 +/- 1 Torr) resulted in marked hemodynamic alterations. Profound bradycardia and decreased cardiac output in addition to increases in mean arterial blood pressure and total peripheral resistance were observed. V1 vasopressinergic antagonism during 10% CO2 had no effect on heart rate but greatly increased cardiac output. In addition, blood pressure fell and resistance was decreased below prehypercapnic levels. These data suggest that a number of the hemodynamic alterations associated with severe hypercapnic acidosis in the conscious rat may be mediated by the peripheral cardiovascular effects of enhanced AVP release.


2021 ◽  
pp. 002367722110018
Author(s):  
Yuri K Sinzato ◽  
Eduardo Klöppel ◽  
Carolina A Miranda ◽  
Verônyca G Paula ◽  
Larissa F Alves ◽  
...  

Animal models are widely used for studying diabetes in translational research. However, methods for induction of diabetes are conflicting with regards to their efficacy, reproducibility and cost. A comparison of outcomes between the diabetic models is still unknown, especially full-term pregnancy.To understand the comparison, we analyzed the streptozotocin (STZ)-induced diabetes at three life-different moments during the neonatal period in Sprague–Dawley female rats: at the first (D1), second (D2) and fifth (D5) day of postnatal life. At adulthood (90 days; D90), the animals were submitted to an oral glucose tolerance test (OGTT) for diabetic status confirmation. The diabetic and control rats were mated and sacrificed at full-term pregnancy for different analyses. Group D1 presented a higher mortality percentage after STZ administration than groups D2 and D5. All diabetic groups presented higher blood glucose levels as compared to those of the control group, while group D5 had higher levels of glycemia compared with other groups during OGTT. The diabetic groups showed impaired reproductive outcomes compared with the control group. Group D1 had lower percentages of mated rats and D5 showed a lower percentage of a full-term pregnancy. Besides that, these two groups also showed the highest percentages of inadequate fetal weight. In summary, although all groups fulfill the diagnosis criteria for diabetes in adult life, in our investigation diabetes induced on D5 presents lower costs and higher efficacy and reproducibility for studies involving diabetes-complicated pregnancy.


2003 ◽  
Vol 94 (5) ◽  
pp. 1949-1954 ◽  
Author(s):  
Philippe Reix ◽  
Julie Arsenault ◽  
Valérie Dôme ◽  
Pierre-Hugues Fortier ◽  
Joëlle Rouillard Lafond ◽  
...  

Our laboratory previously reported that active glottal closure was present in 90% of spontaneous central apneas in premature lambs while maintaining a high-apneic lung volume (Renolleau S, Letourneau P, Niyonsenga T, and Praud JP. Am J Respir Crit Care Med 159: 1396–1404, 1999.) The present study aimed at testing whether this mechanism limits postapnea oxygen desaturation. Four premature lambs were instrumented for recording states of alertness, thyroarytenoid muscle and diaphragm electromyographic (EMG) activity, nasal airflow, lung volume changes, and pulse oximetry. One thousand four hundred fifty-two spontaneous central apneas (isolated or during periodic breathing) were analyzed in nonsedated lambs. Apneas, with high lung volume maintained by active glottal closure, were compared with apneas, with a tracheostomy opened at apnea onset. Oxygen desaturation slopes were lower when high-apneic lung volume was actively maintained during both wakefulness and quiet sleep. Furthermore, oxygen desaturation slopes were lower after isolated apneas with continuous thyroarytenoid EMG during wakefulness, compared with apneas with noncontinuous thyroarytenoid EMG (= glottis opened shortly after apnea onset). These results highlight the importance of maintaining high-alveolar oxygen stores during central apneas by active glottal closure to limit desaturation in newborns.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tiziana Imbriglio ◽  
Remy Verhaeghe ◽  
Nico Antenucci ◽  
Stefania Maccari ◽  
Giuseppe Battaglia ◽  
...  

AbstractmGlu5 metabotropic glutamate receptors are highly expressed and functional in the early postnatal life, and are known to positively modulate NMDA receptor function. Here, we examined the expression of NMDA receptor subunits and interneuron-related genes in the prefrontal cortex and hippocampus of mGlu5−/− mice and wild-type littermates at three developmental time points (PND9, − 21, and − 75). We were surprised to find that expression of all NMDA receptor subunits was greatly enhanced in mGlu5−/− mice at PND21. In contrast, at PND9, expression of the GluN2B subunit was enhanced, whereas expression of GluN2A and GluN2D subunits was reduced in both regions. These modifications were transient and disappeared in the adult life (PND75). Changes in the transcripts of interneuron-related genes (encoding parvalbumin, somatostatin, vasoactive intestinal peptide, reelin, and the two isoforms of glutamate decarboxylase) were also observed in mGlu5−/− mice across postnatal development. For example, the transcript encoding parvalbumin was up-regulated in the prefrontal cortex of mGlu5−/− mice at PND9 and PND21, whereas it was significantly reduced at PND75. These findings suggest that in mGlu5−/− mice a transient overexpression of NMDA receptor subunits may compensate for the lack of the NMDA receptor partner, mGlu5. Interestingly, in mGlu5−/− mice the behavioral response to the NMDA channel blocker, MK-801, was significantly increased at PND21, and largely reduced at PND75. The impact of adaptive changes in the expression of NMDA receptor subunits should be taken into account when mGlu5−/− mice are used for developmental studies.


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